Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
1.
Environ Sci Technol ; 57(13): 5337-5348, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36940419

RESUMO

Historical mining activities in Svalbard (79°N/12°E) have caused local mercury (Hg) contamination. To address the potential immunomodulatory effects of environmental Hg on Arctic organisms, we collected newborn barnacle goslings (Branta leucopsis) and herded them in either a control or mining site, differing in Hg levels. An additional group at the mining site was exposed to extra inorganic Hg(II) via supplementary feed. Hepatic total Hg concentrations differed significantly between the control (0.011 ± 0.002 mg/kg dw), mine (0.043 ± 0.011 mg/kg dw), and supplementary feed (0.713 ± 0.137 mg/kg dw) gosling groups (average ± standard deviation). Upon immune challenge with double-stranded RNA (dsRNA) injection, endpoints for immune responses and oxidative stress were measured after 24 h. Our results indicated that Hg exposure modulated the immune responses in Arctic barnacle goslings upon a viral-like immune challenge. Increased exposure to both environmental as well as supplemental Hg reduced the level of natural antibodies, suggesting impaired humoral immunity. Hg exposure upregulated the expression of proinflammatory genes in the spleen, including inducible nitric oxide synthase (iNOS) and interleukin 18 (IL18), suggesting Hg-induced inflammatory effects. Exposure to Hg also oxidized glutathione (GSH) to glutathione disulfide (GSSG); however, goslings were capable of maintaining the redox balance by de novo synthesis of GSH. These adverse effects on the immune responses indicated that even exposure to low, environmentally relevant levels of Hg might affect immune competence at the individual level and might even increase the susceptibility of the population to infections.


Assuntos
Mercúrio , Thoracica , Animais , Gansos/metabolismo , Thoracica/metabolismo , Svalbard , Regiões Árticas , Imunidade
2.
JACC Cardiovasc Interv ; 15(11): 1140-1149, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35680194

RESUMO

BACKGROUND: The work-up for transcatheter aortic valve replacement (TAVR) currently uses computed tomography to evaluate the annulus diameter and peripheral vascular access plus invasive coronary angiography (ICA) to assess significant coronary artery disease (CAD). ICA might partially be redundant with the use of coronary computed tomography angiography (CCTA). Prior studies found an improvement of the diagnostic accuracy of CCTA with the use of computed tomography-derived fractional flow reserve (CT-FFR). OBJECTIVES: The aim of this study was to assess the diagnostic performance of CT-FFR for the diagnosis of CAD in the work-up for TAVR. METHODS: Consecutive patients with severe symptomatic aortic valve stenosis who underwent TAVR work-up between 2015 and 2019 were included in this retrospective cross-sectional study. All patients underwent CCTA and ICA within 3 months, and the diagnostic performance of both CCTA and CT-FFR was assessed using ICA as the reference. RESULTS: Seventy-six of the 338 patients included in the analysis had ≥1 significant coronary stenosis on ICA. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy per patient were 76.9%, 64.5%, 34.0%, 92.1%, and 66.9% for CCTA and 84.6%, 88.3%, 63.2%, 96.0%, and 87.6% for CT-FFR. The area under the receiver-operating characteristic curve was significantly different between CCTA and CT-FFR (0.84 vs 0.90, P = 0.02). A CT-FFR-guided approach could avoid ICA in 57.1% versus 43.6% of patients using CCTA. CONCLUSIONS: CT-FFR significantly improves the diagnostic accuracy of CCTA without additional testing and increases the proportion of patients in whom ICA could have been safely avoided. It has the potential to be integrated in the current clinical work-up for TAVR for diagnosing stable CAD requiring treatment.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Substituição da Valva Aórtica Transcateter , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/terapia , Estudos Transversais , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
3.
Nano Lett ; 21(19): 8213-8219, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34597058

RESUMO

Controlling magnon densities in magnetic materials enables driving spin transport in magnonic devices. We demonstrate the creation of large, out-of-equilibrium magnon densities in a thin-film magnetic insulator via microwave excitation of coherent spin waves and subsequent multimagnon scattering. We image both the coherent spin waves and the resulting incoherent magnon gas using scanning-probe magnetometry based on electron spins in diamond. We find that the gas extends unidirectionally over hundreds of micrometers from the excitation stripline. Surprisingly, the gas density far exceeds that expected for a boson system following a Bose-Einstein distribution with a maximum value of the chemical potential. We characterize the momentum distribution of the gas by measuring the nanoscale spatial decay of the magnetic stray fields. Our results show that driving coherent spin waves leads to a strong out-of-equilibrium occupation of the spin-wave band, opening new possibilities for controlling spin transport and magnetic dynamics in target directions.

4.
Environ Pollut ; 289: 117909, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371263

RESUMO

The Wood mouse (Apodemus sylvaticus) is a widespread mammalian species that acts as a reservoir host for multiple infections, including zoonotic diseases. Exposure to immunotoxins, like for instance trace metals, may reduce the ability of the host to mount proper responses to pathogens, potentially increasing the transmission and prevalence of infections. Antibody-mediated responses are crucial in preventing and limiting infections, and the quantification of the primary antibody response is considered a sensitive predictor of immunosuppression. The current study aims to investigate effects of cadmium exposure on the antibody-mediated responses of wood mice inhabiting polluted and non-polluted areas in the Netherlands. Wood mice were captured alive at different locations and immunized to sheep red blood cells (SRBC) to induce a primary antibody response. SRBC-specific antibody-producing cells, or plaque forming cells (PFC), were quantified and related to kidney cadmium levels. Differential circulating main leukocyte populations were also characterised. Cadmium concentrations in mice kidneys differed between mice captured at different locations, and increased with individual body mass, likely associated with age-related time of exposure. Effect of cadmium was apparent on the percentages of B cell counts in blood. Because of potential natural immune heterogeneity between wild rodent populations, mice immune responses were analysed and compared grouped by captured locations. Capture location had significant effect on the total counts of white blood cells. Increasing cadmium exposure in wood mice captured from polluted sites was associated with a decrease of splenic PFC counts. This field research shows that wood mice antibody responses can be impaired by cadmium exposure, even at low environmental levels, by affecting B cell functioning mainly. Impaired B cell function can make exposed mice more susceptible to infections, potentially increasing the reservoir function of their populations. It also shows that immunomodulatory effects in the field should be assessed site specifically.


Assuntos
Formação de Anticorpos , Cádmio , Animais , Cádmio/análise , Exposição Ambiental , Camundongos , Murinae , Países Baixos , Ovinos
5.
Environ Toxicol Chem ; 40(10): 2813-2824, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34288095

RESUMO

Mercury (Hg) is a toxic trace metal ubiquitously distributed in the environment. Inorganic mercury (as HgCl2 ) can cause immunotoxicity in birds, but the mechanisms of action are still not fully resolved, especially with respect to responses to viral infections. To investigate the potential immunomodulatory effects of Hg2+ on specific cell types of the avian immune system, chicken macrophage (HD-11) and B-lymphocyte (DT40) cell lines were applied as in vitro models for the innate and adaptive immune systems, respectively. The cells were stimulated with synthetic double-stranded RNA, which can be recognized by toll-like receptor-3 to mimic a viral infection. The Hg2+ showed concentration-dependent cytotoxicity in both cell lines, with similar median effect concentrations at 30 µM. The cytotoxicity of Hg2+ was closely related to glutathione (GSH) depletion and reactive oxygen species induction, whereas the de novo synthesis of GSH acted as a primary protective strategy. Nitric oxide produced by activated macrophages was strongly inhibited by Hg2+ , and was also influenced by cellular GSH levels. Cell proliferation, gene expression of microRNA-155, and cellular IgM levels in B cells were decreased at noncytotoxic Hg2+ concentrations. The secretion of antiviral interferon-α was induced by Hg2+ in both cell lines. Overall, our results suggest that Hg2+ exposure can cause immunomodulatory effects in birds by disrupting immune cell proliferation and cytokine production, and might result in disorders of the avian immune system. Environ Toxicol Chem 2021;40:2813-2824. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Assuntos
Mercúrio , Animais , Linfócitos B/metabolismo , Linhagem Celular , Galinhas/metabolismo , Cloretos , Glutationa/metabolismo , Macrófagos , Mercúrio/toxicidade
6.
Environ Toxicol Chem ; 39(5): 1060-1070, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32124477

RESUMO

Elevated levels of lead have been found in waterfowl, due to human activities. Lead may cause immunomodulatory effects, but the mechanisms are largely unknown, especially after viral challenges. To characterize avian immunomodulatory hazards of lead (Pb)2+ , we used chicken macrophage (HD-11) and B-lymphocyte (DT40) cell lines, as in vitro models for the innate and adaptive immune systems, respectively. The cells were activated via toll-like receptor-3 by polyinosinic-polycytidylic acid sodium salt (poly I:C), mimicking viral infections. Our results indicate that Pb2+ is cytotoxic to both cell lines, macrophages being more sensitive. De novo synthesis of glutathione plays an important role in protecting macrophages from Pb2+ intoxication, which might also be closely involved in the induction of nitric oxide after Pb2+ exposure. Stimulatory effects on cell proliferation were noticed at noncytotoxic Pb2+ concentrations as well. Exposure to Pb2+ could also affect the inflammatory status by inhibiting the pro-inflammatory interferon (IFN)-γ while promoting the production of anti-inflammatory type I IFNs in both macrophages and B-cells, and increasing intracellular IgM levels in B-cells. These results suggest that the immunomodulatory effects of Pb2+ in birds are probably closely associated with disruption of immune cell proliferation and cytokine production, potentially causing disorders of the avian immune system. Environ Toxicol Chem 2020;39:1060-1070. © 2020 SETAC.


Assuntos
Linfócitos B/virologia , Galinhas/virologia , Chumbo/toxicidade , Macrófagos/virologia , Animais , Linfócitos B/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Espécies Reativas de Oxigênio/metabolismo
7.
Environ Pollut ; 252(Pt A): 155-162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146230

RESUMO

Sewage sludge contains Ag2S-NPs causing NP exposure of soil fauna when sludge is applied as soil amendment. Earthworm bioturbation is an important process affecting many soil functions. Bioturbation may be affected by the presence of Ag2S-NPs, but the earthworm activity itself may also influence the displacement of these NPs that otherwise show little transport in the soil. The aim of this study was to determine effects of Ag2S-NPs on earthworm bioturbation and effect of this bioturbation on the vertical distribution of Ag2S-NPs. Columns (12 cm) of a sandy loamy soil with and without Lumbricus rubellus were prepared with and without 10 mg Ag kg-1, applied as Ag2S-NPs in the top 2 cm of the soil, while artificial rainwater was applied at ∼1.2 mm day-1. The soil columns were sampled at three depths weekly for 28 days and leachate collected from the bottom. Total Ag measurements showed more displacement of Ag to deeper soil layers in the columns with earthworms. The application of rain only did not significantly affect Ag transport in the soil. No Ag was detected in column leachates. X-ray tomography showed that changes in macro porosity and pore size distribution as a result of bioturbation were not different between columns with and without Ag2S-NPs. Earthworm activity was therefore not affected by Ag2S-NPs at the used exposure concentration. Ag concentrations along the columns and the earthworm density allowed the calculation of the bioturbation rate. The effect on the Ag transport in the soil shows that earthworm burrowing activity is a relevant process that must be taken into account when studying the fate of nanoparticles in soils.


Assuntos
Nanopartículas Metálicas/química , Oligoquetos/metabolismo , Prata/análise , Poluentes do Solo/análise , Solo/química , Animais , Esgotos/química , Tomografia por Raios X
8.
Nano Lett ; 19(6): 3987-3992, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31136192

RESUMO

Diamond membrane devices containing optically coherent nitrogen-vacancy (NV) centers are key to enable novel cryogenic experiments such as optical ground-state cooling of hybrid spin-mechanical systems and efficient entanglement distribution in quantum networks. Here, we report on the fabrication of a (3.4 ± 0.2) µm thin, smooth (surface roughness rq < 0.4 nm over an area of 20 µm by 30 µm) diamond membrane containing individually resolvable, narrow linewidth (< 100 MHz) NV centers. We fabricate this sample via a combination of high-energy electron irradiation, high-temperature annealing, and an optimized etching sequence found via a systematic study of the diamond surface evolution on the microscopic level in different etch chemistries. Although our particular device dimensions are optimized for cavity-enhanced entanglement generation between distant NV centers in open, tunable microcavities, our results have implications for a broad range of quantum experiments that require the combination of narrow optical transitions and micrometer-scale device geometry.

9.
J Appl Toxicol ; 39(7): 992-1001, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30828855

RESUMO

Toxic trace metals are widespread contaminants that are potentially immunotoxic even at environmentally low exposure levels. They can modulate the immunity to infections, e.g., in wildlife species living in contaminated areas. The diverse immune cell types can be differentially affected by the exposure leading to the modulation of specific protective mechanisms. Macrophages and mast cells, part of the innate immune system, trigger immune responses and perform particular effector functions. The present study compared toxicological and functional effects of cadmium in two models of murine macrophages (RAW264.7 and NR8383 cell lines) and two models of murine mast cells (MC/9 and RBL-2H3 cell lines). Cadmium was selected as a model compound because its known potential to induce reactive oxygen species and its relevance as an environmental contaminant. Mechanisms of toxicity, such as redox imbalance and apoptosis induction were measured in stationary cells, while functional outcome effects were measured in activated cells. Cadmium-depleted glutathione antioxidant in all four cell lines tested although reactive oxygen species was not significantly increased. Mast cells had full dose-response depletion of glutathione below cytotoxic levels while in macrophages the depletion was not complete. Functional endpoints tumour necrosis factor-alpha and nitrite production in lipopolysaccharide-activated macrophages were increased by cadmium exposure. In contrast, mast cell lipopolysaccharide-induced tumour necrosis factor-alpha and IgE-mediated histamine release were reduced by cadmium. These data indicate potentially differential effects of cadmium among murine innate immune cell types, where mast cells would be more susceptible to oxidative stress and their function might be at a higher risk to be modulated compared to macrophages.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Imunidade Inata/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Mastócitos/imunologia , Camundongos , Células RAW 264.7 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Toxicol Sci ; 162(1): 79-88, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29106689

RESUMO

In literature, varying and sometimes conflicting effects of physicochemical properties of nanoparticles (NPs) are reported on their uptake and effects in organisms. To address this, small- and medium-sized (20 and 50 nm) silver nanoparticles (AgNPs) with specified different surface coating/charges were synthesized and used to systematically assess effects of NP-properties on their uptake and effects in vitro. Silver nanoparticles were fully characterized for charge and size distribution in both water and test media. Macrophage cells (RAW 264.7) were exposed to these AgNPs at different concentrations (0-200 µg/ml). Uptake dynamics, cell viability, induction of tumor necrosis factor (TNF)-α, ATP production, and reactive oxygen species (ROS) generation were assessed. Microscopic imaging of living exposed cells showed rapid uptake and subcellular cytoplasmic accumulation of AgNPs. Exposure to the tested AgNPs resulted in reduced overall viability. Influence of both size and surface coating (charge) was demonstrated, with the 20-nm-sized AgNPs and bovine serum albumin (BSA)-coated (negatively charged) AgNPs being slightly more toxic. On specific mechanisms of toxicity (TNF-α and ROS production) however, the AgNPs differed to a larger extent. The highest induction of TNF-α was found in cells exposed to the negatively charged AgNP_BSA, both sizes (80× higher than control). Reactive oxygen species induction was only significant with the 20 nm positively charged AgNP_Chit.


Assuntos
Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Prata/química , Prata/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Macrófagos/metabolismo , Camundongos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Tamanho da Partícula , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Prata/metabolismo , Propriedades de Superfície
12.
Trials ; 18(1): 362, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28768538

RESUMO

BACKGROUND: Some patients with chronic abdominal pain suffer from an anterior cutaneous nerve entrapment syndrome (ACNES). This somewhat illusive syndrome is thought to be caused by the entrapment of end branches of the intercostal nerves residing in the abdominal wall. If ACNES is suspected, a local injection of an anesthetic agent may offer relief. If pain is recurrent following multiple-injection therapy, an anterior neurectomy entailing removal of the entrapped nerve endings may be considered. After 1 year, a 70% success rate has been reported. Research on minimally invasive alternative treatments is scarce. Pulsed radiofrequency (PRF) treatment is a relatively new treatment for chronic pain syndromes. An electromagnetic field is applied around the nerve in the hope of leading to pain relief. This randomized controlled trial compares the effect of PRF treatment and neurectomy in patients with ACNES. METHODS: Adult ACNES patients having short-lived success following injections are randomized to PRF or neurectomy. At the 8-week follow-up visit, unsuccessful PRF patients are allowed to cross over to a neurectomy. Primary outcome is pain relief after either therapy. Secondary outcomes include patient satisfaction, quality of life, use of analgesics and unanticipated adverse events. The study is terminated 6 months after receiving the final procedure. DISCUSSION: Since academic literature on minimally invasive techniques is lacking, well-designed trials are needed to optimize results of treatment for ACNES. This is the first large, randomized controlled, proof-of-concept trial comparing two therapy techniques in ACNES patients. The first patient was included in October 2015. The expected trial deadline is December 2017. If effective, PRF may be incorporated into the ACNES treatment algorithm, thus minimizing the number of patients requiring surgery. TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), NTR5131 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5131 ). Registered on 15 April 2015.


Assuntos
Dor Abdominal/cirurgia , Parede Abdominal/inervação , Ablação por Cateter , Dor Crônica/cirurgia , Denervação/métodos , Nervos Intercostais/cirurgia , Síndromes de Compressão Nervosa/cirurgia , Pele/inervação , Dor Abdominal/diagnóstico , Dor Abdominal/fisiopatologia , Analgésicos/uso terapêutico , Ablação por Cateter/efeitos adversos , Dor Crônica/diagnóstico , Dor Crônica/fisiopatologia , Protocolos Clínicos , Denervação/efeitos adversos , Humanos , Nervos Intercostais/fisiopatologia , Síndromes de Compressão Nervosa/diagnóstico , Síndromes de Compressão Nervosa/fisiopatologia , Países Baixos , Medição da Dor , Dor Pós-Operatória/etiologia , Satisfação do Paciente , Estudo de Prova de Conceito , Estudos Prospectivos , Qualidade de Vida , Projetos de Pesquisa , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
14.
Toxicol In Vitro ; 29(7): 1701-10, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26145586

RESUMO

To obtain insight in translocation of nanoparticles across the placental barrier, translocation was studied for one positively and two negatively charged polystyrene nanoparticles (PS-NPs) of similar size in an in vitro model. The model consisted of BeWo b30 cells, derived from a human choriocarcinoma grown on a transwell insert forming a cell layer that separates an apical from a basolateral compartment. PS-NPs were characterized with respect to size, surface charge, morphology and protein corona. Translocation of PS-NPs was not related to PS-NP charge. Two PS-NPs were translocated across the BeWo transwell model to a lower extent than amoxicillin, a model compound known to be translocated over the placental barrier to only a limited extent, whereas one PS-NP showed a slightly higher translocation. Studies on the effect of transporter inhibitors on the translocation of the PS-NPs indicated that their translocation was not mediated by known transporters and mainly dependent on passive diffusion. It is concluded that the BeWo b30 model can be used as an efficient method to get an initial qualitative impression about the capacity of NPs to translocate across the placental barrier and set priorities in further in vivo studies on translocation of NPs to the fetus.


Assuntos
Nanopartículas/metabolismo , Placenta/metabolismo , Poliestirenos/metabolismo , Transporte Biológico , Linhagem Celular Tumoral , Feminino , Humanos , Gravidez
15.
J Nanopart Res ; 17(5): 231, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26028989

RESUMO

The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral, positive and negative) using a Caco-2/HT29-MTX in vitro intestinal translocation model. The NPs translocated in a surface charge-dependent manner. The present study aimed to validate this in vitro intestinal model by an in vivo study. For this, rats were orally exposed to a single dose of these polystyrene NPs and the uptake in organs was determined. A negatively charged NP was taken up more than other NPs, with the highest amounts in kidney (37.4 µg/g tissue), heart (52.8 µg/g tissue), stomach wall (98.3 µg/g tissue) and small intestinal wall (94.4 µg/g tissue). This partly confirms our in vitro findings, where the same NPs translocated to the highest extent. The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6-12.3 %). Therefore, the integrated in vitro model cannot be used for a direct prediction of the bioavailability of orally administered NPs. However, the model can be used for prioritizing NPs before further in vivo testing for risk assessment.

16.
BMJ ; 350: h846, 2015 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-25713015

RESUMO

OBJECTIVE: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. DESIGN: Multicentre randomised controlled equivalence trial. SETTING: 15 hospitals in the Netherlands. PARTICIPANTS: Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data. INTERVENTION: Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour. MAIN OUTCOME MEASURES: Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome. RESULTS: 1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference -2.8, 95% confidence interval -6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference -10.4, -13.9 to -7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups. CONCLUSION: In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia. TRIAL REGISTRATION: Netherlands Trial Register NTR2551.


Assuntos
Analgesia Epidural , Analgesia Obstétrica/métodos , Analgesia Controlada pelo Paciente , Analgésicos Opioides/administração & dosagem , Piperidinas/administração & dosagem , Adulto , Analgésicos Opioides/farmacocinética , Área Sob a Curva , Estudos Cross-Over , Feminino , Humanos , Países Baixos , Manejo da Dor/métodos , Medição da Dor , Satisfação do Paciente , Piperidinas/farmacocinética , Gravidez , Remifentanil , Equivalência Terapêutica , Adulto Jovem
17.
Planta ; 236(6): 1955-65, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23132522

RESUMO

In order to obtain a tuberous root-specific promoter to be used in the transformation of cassava, a 1,728 bp sequence containing the cassava granule-bound starch synthase (GBSSI) promoter was isolated. The sequence proved to contain light- and sugar-responsive cis elements. Part of this sequence (1,167 bp) was cloned into binary vectors to drive expression of the firefly luciferase gene. Cassava cultivar Adira 4 was transformed with this construct or a control construct in which the luciferase gene was cloned behind the 35S promoter. Luciferase activity was measured in leaves, stems, roots and tuberous roots. As expected, the 35S promoter induced luciferase activity in all organs at similar levels, whereas the GBSSI promoter showed very low expression in leaves, stems and roots, but very high expression in tuberous roots. These results show that the cassava GBSSI promoter is an excellent candidate to achieve tuberous root-specific expression in cassava.


Assuntos
Manihot/enzimologia , Regiões Promotoras Genéticas/genética , Sintase do Amido/genética , Sequência de Bases , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Luciferases/genética , Luciferases/metabolismo , Manihot/genética , Manihot/crescimento & desenvolvimento , Meristema/enzimologia , Meristema/genética , Meristema/crescimento & desenvolvimento , Dados de Sequência Molecular , Especificidade de Órgãos , Folhas de Planta/enzimologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Caules de Planta/enzimologia , Caules de Planta/genética , Caules de Planta/crescimento & desenvolvimento , Tubérculos/enzimologia , Tubérculos/genética , Tubérculos/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Análise de Sequência de DNA , Sintase do Amido/metabolismo
18.
Environ Toxicol Chem ; 30(4): 973-80, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21309018

RESUMO

Current petroleum risk assessment considers only narcosis as the mode of action, but several studies have demonstrated that oils contain compounds with dioxin-like, estrogenic or antiestrogenic, and androgenic or antiandrogenic activities. The present study is the third in a series investigating the specific toxic effects of 11 crude oils and refined products. By employing recombinant mammalian cells stably transfected with the human estrogen receptor alpha (ERα) or beta (ERß), and expressing the luciferase protein (ERα-U2OS-Luc and ERß-U2OS-Luc assay), the estrogenicity or antiestrogenicity of oils was studied. All oils, except for two refined oils and one crude oil, induced estrogenic responses. The calculated estrogenic potencies of the oils were six to nine orders of magnitude lower than the potency of 17ß-estradiol (E2). Upon coexposure to a fixed concentration of E2 and increasing concentrations of oils, additive, antagonistic, and synergistic effects were revealed. One nautical fuel oil was tested in the human breast carcinoma cell line MCF-7, in which it induced cell proliferation up to 70% relative to the maximal induction by E2. At its minimum effect concentration of 25 mg/L, the oil was also capable of inducing mRNA expression of the estrogen-dependent protein pS2 by a factor of two. The present results indicate that oils naturally contain potentially endocrine-disrupting compounds that are able to influence the estrogenicity of other compounds and may cause biological responses beyond receptor binding.


Assuntos
Disruptores Endócrinos/toxicidade , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Petróleo/toxicidade , Linhagem Celular Tumoral , Humanos , Medição de Risco
19.
Ecotoxicol Environ Saf ; 73(8): 1829-34, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20863569

RESUMO

The DR-H4IIE.Luc bioassay is based on the ability of dioxin and dioxin-like contaminants to activate the AhR and its signal transduction pathway, a mechanism through which these contaminants elicit their toxic effects. The bioassay was used to examine the total dioxin-equivalent (TEQ) toxicity in gonads and livers of cod females from the southern Baltic Sea. The bioassay-derived TEQ-luc was measured after 24-h and 48-h exposure periods. Mean concentrations in the 24-h bioassay were 95 and 35 pg TEQ-luc g(-1) lipid in gonads and livers, respectively, and 58 and 38 pg TEQ-luc g(-1) lipid in the 48-h bioassay, respectively. The 48-h TEQ-luc levels displayed significant relationships with ΣPCB(7) and selected PCB congeners but not with the TEQ(DLPCB-REP). Levels in gonads approached 10% of the LC50 for developing larvae of other marine fish, yet the impact on survival of the cod during its early life remains to be assessed in a future.


Assuntos
Bioensaio/métodos , Dioxinas/toxicidade , Gadus morhua/metabolismo , Gônadas/efeitos dos fármacos , Fígado/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Gadus morhua/crescimento & desenvolvimento , Gônadas/metabolismo , Fígado/metabolismo , Oceanos e Mares , Polônia , Fatores de Tempo , Testes de Toxicidade
20.
Chemosphere ; 75(11): 1531-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19376559

RESUMO

Within the REACH regulatory framework in the EU, quantitative structure-activity relationships (QSAR) models are expected to help reduce the number of animals used for experimental testing. The objective of this study was to develop QSAR models to describe the acute toxicity of organothiophosphate pesticides to aquatic organisms. Literature data sets for acute toxicity data of organothiophosphates to fish and one data set from experiments with 15 organothiophosphates on Daphniamagna performed in the present study were used to establish QSARs based on quantum mechanically derived molecular descriptors. The logarithm of the octanol/water partition coefficient, logK(ow,) the energy of the lowest unoccupied molecular orbital, E(lumo), and the energy of the highest occupied molecular orbital, E(homo) were used as descriptors. Additionally, it was investigated if toxicity data for the invertebrate D. magna could be used to build a QSAR model to predict toxicity to fish. Suitable QSAR models (0.80

Assuntos
Carpas/fisiologia , Daphnia/efeitos dos fármacos , Compostos Organotiofosforados/toxicidade , Resíduos de Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Modelos Biológicos , Modelos Químicos , Compostos Organotiofosforados/química , Resíduos de Praguicidas/química , Relação Quantitativa Estrutura-Atividade , Testes de Toxicidade Aguda , Poluentes Químicos da Água/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...