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1.
NanoImpact ; 33: 100496, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38266914

RESUMO

There have been major advances in the science to predict the likely environmental concentrations of nanomaterials, which is a key component of exposure and subsequent risk assessment. Considerable progress has been since the first Material Flow Analyses (MFAs) in 2008, which were based on very limited information, to more refined current tools that take into account engineered nanoparticle (ENP) size distribution, form, dynamic release, and better-informed release factors. These MFAs provide input for all environmental fate models (EFMs), that generate estimates of particle flows and concentrations in various environmental compartments. While MFA models provide valuable information on the magnitude of ENP release, they do not account for fate processes, such as homo- and heteroaggregation, transformations, dissolution, or corona formation. EFMs account for these processes in differing degrees. EFMs can be divided into multimedia compartment models (e.g., atmosphere, waterbodies and their sediments, soils in various landuses), of which there are currently a handful with varying degrees of complexity and process representation, and spatially-resolved watershed models which focus on the water and sediment compartments. Multimedia models have particular applications for considering predicted environmental concentrations (PECs) in particular regions, or for developing generic "fate factors" (i.e., overall persistence in a given compartment) for life-cycle assessment. Watershed models can track transport and eventual fate of emissions into a flowing river, from multiple sources along the waterway course, providing spatially and temporally resolved PECs. Both types of EFMs can be run with either continuous sources of emissions and environmental conditions, or with dynamic emissions (e.g., temporally varying for example as a new nanomaterial is introduced to the market, or with seasonal applications), to better understand the situations that may lead to peak PECs that are more likely to result in exceedance of a toxicological threshold. In addition, bioaccumulation models have been developed to predict the internal concentrations that may accumulate in exposed organisms, based on the PECs from EFMs. The main challenge for MFA and EFMs is a full validation against observed data. To date there have been no field studies that can provide the kind of dataset(s) needed for a true validation of the PECs. While EFMs have been evaluated against a few observations in a small number of locations, with results that indicate they are in the right order of magnitude, there is a great need for field data. Another major challenge is the input data for the MFAs, which depend on market data to estimate the production of ENPs. The current information has major gaps and large uncertainties. There is also a lack of robust analytical techniques for quantifying ENP properties in complex matrices; machine learning may be able to fill this gap. Nevertheless, there has been major progress in the tools for generating PECs. With the emergence of nano- and microplastics as a leading environmental concern, some EFMs have been adapted to these materials. However, caution is needed, since most nano- and microplastics are not engineered, therefore their characteristics are difficult to generalize, and there are new fate and transport processes to consider.


Assuntos
Microplásticos , Nanoestruturas , Plásticos , Modelos Teóricos , Medição de Risco
2.
J Clin Med ; 12(20)2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37892576

RESUMO

Septic shock is characterized by endothelial dysfunction, leading to tissue edema and organ failure. Heparan sulfate (HS) is essential for vascular barrier integrity, possibly via albumin as a carrier. We hypothesized that supplementing fluid resuscitation with HS would improve endothelial barrier function, thereby reducing organ edema and injury in a rat pneumosepsis model. Following intratracheal inoculation with Streptococcus pneumoniae, Sprague Dawley rats were randomized to resuscitation with a fixed volume of either Ringer's Lactate (RL, standard of care), RL supplemented with 7 mg/kg HS, 5% human albumin, or 5% human albumin supplemented with 7 mg/kg HS (n = 11 per group). Controls were sham inoculated animals. Five hours after the start of resuscitation, animals were sacrificed. To assess endothelial permeability, 70 kD FITC-labelled dextran was administered before sacrifice. Blood samples were taken to assess markers of endothelial and organ injury. Organs were harvested to quantify pulmonary FITC-dextran leakage, organ edema, and for histology. Inoculation resulted in sepsis, with increased lactate levels, pulmonary FITC-dextran leakage, pulmonary edema, and pulmonary histologic injury scores compared to healthy controls. RL supplemented with HS did not reduce median pulmonary FITC-dextran leakage compared to RL alone (95.1 CI [62.0-105.3] vs. 87.1 CI [68.9-139.3] µg/mL, p = 0.76). Similarly, albumin supplemented with HS did not reduce pulmonary FITC-dextran leakage compared to albumin (120.0 [93.8-141.2] vs. 116.2 [61.7 vs. 160.8] µg/mL, p = 0.86). No differences were found in organ injury between groups. Heparan sulfate, as an add-on therapy to RL or albumin resuscitation, did not reduce organ or endothelial injury in a rat pneumosepsis model. Higher doses of heparan sulfate may decrease organ and endothelial injury induced by shock.

3.
BMJ Open ; 13(8): e073126, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37591644

RESUMO

INTRODUCTION: Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway ('The Hague RTI Care Bridge') developed with the aim to treat and coordinate care for these patients outside the hospital. METHODS AND ANALYSIS: This is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN68786381.


Assuntos
Delírio , Prestação Integrada de Cuidados de Saúde , Pneumonia , Infecções Respiratórias , Humanos , Idoso , Procedimentos Clínicos , Estudos Prospectivos , Qualidade de Vida , Pneumonia/terapia , Hospitais , Delírio/terapia
4.
J Inherit Metab Dis ; 2023 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-37455357

RESUMO

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare neurometabolic disorder caused by disruption of the gamma-aminobutyric acid (GABA) pathway. A more detailed understanding of its pathophysiology, beyond the accumulation of GABA and gamma-hydroxybutyric acid (GHB), will increase our understanding of the disease and may support novel therapy development. To this end, we compared biochemical body fluid profiles from SSADHD patients with controls using next-generation metabolic screening (NGMS). Targeted analysis of NGMS data from cerebrospinal fluid (CSF) showed a moderate increase of aspartic acid, glutaric acid, glycolic acid, 4-guanidinobutanoic acid, and 2-hydroxyglutaric acid, and prominent elevations of GHB and 4,5-dihydroxyhexanoic acid (4,5-DHHA) in SSADHD samples. Remarkably, the intensities of 4,5-DHHA and GHB showed a significant positive correlation in control CSF, but not in patient CSF. In an established zebrafish epilepsy model, 4,5-DHHA showed increased mobility that may reflect limited epileptogenesis. Using untargeted metabolomics, we identified 12 features in CSF with high biomarker potential. These had comparable increased fold changes as GHB and 4,5-DHHA. For 10 of these features, a similar increase was found in plasma, urine and/or mouse brain tissue for SSADHD compared to controls. One of these was identified as the novel biomarker 4,5-dihydroxyheptanoic acid. The intensities of selected features in plasma and urine of SSADHD patients positively correlated with the clinical severity score of epilepsy and psychiatric symptoms of those patients, and also showed a high mutual correlation. Our findings provide new insights into the (neuro)metabolic disturbances in SSADHD and give leads for further research concerning SSADHD pathophysiology.

5.
Toxics ; 10(7)2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35878259

RESUMO

Nanotechnology is a growing megatrend in industrial production and innovations. Many applications utilize engineered nanomaterials (ENMs) that are potentially released into the atmospheric environment, e.g., via direct stack emissions from production facilities. Limited information exists on adverse effects such ENM releases may have on human health and the environment. Previous exposure modeling approaches have focused on large regional compartments, into which the released ENMs are evenly mixed. However, due to the localization of the ENM release and removal processes, potentially higher airborne concentrations and deposition fluxes are obtained around the production facilities. Therefore, we compare the ENM concentrations from a dispersion model to those from the uniformly mixed compartment approach. For realistic release scenarios, we based the modeling on the case study measurement data from two TiO2 nanomaterial handling facilities. In addition, we calculated the distances, at which 50% of the ENMs are deposited, serving as a physically relevant metric to separate the local scale from the regional scale, thus indicating the size of the high exposure and risk region near the facility. As a result, we suggest a local scale compartment to be implemented in the multicompartment nanomaterial exposure models. We also present a computational tool for local exposure assessment that could be included to regulatory guidance and existing risk governance networks.

6.
Sci Adv ; 8(20): eabj3220, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35584216

RESUMO

Until recently, despite being one of the most important sediment transport phenomena on Earth, few direct measurements of turbidity currents existed. Consequently, their structure and evolution were poorly understood, particularly whether they are dense or dilute. Here, we analyze the largest number of turbidity currents monitored to date from source to sink. We show sediment transport and internal flow characteristic evolution as they runout. Observed frontal regions (heads) are fast (>1.5 m/s), thin (<10 m), dense (depth averaged concentrations up to 38%vol), strongly stratified, and dominated by grain-to-grain interactions, or slower (<1 m/s), dilute (<0.01%vol), and well mixed with turbulence supporting sediment. Between these end-members, a transitional flow head exists. Flow bodies are typically thick, slow, dilute, and well mixed. Flows with dense heads stretch and bulk up with dense heads transporting up to 1000 times more sediment than the dilute body. Dense heads can therefore control turbidity current sediment transport and runout into the deep sea.

7.
Case Rep Gastroenterol ; 14(3): 577-585, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250700

RESUMO

Hepatocellular adenomas (HCA) are rare benign tumors of the liver, occurring predominantly in females using oral contraceptives. Our case describes a 66-year-old woman presenting with a palpable mass in her upper abdomen. Contrast-enhanced computed tomography and magnetic resonance imaging showed a large exophytic mass protruding from the caudal border of liver segments IV and V, without visible metastases. Laparoscopic resection of the tumor and gallbladder was performed. Histopathological examination showed a hepatocellular carcinoma with areas of HNF1a-HCA (H-HCA). This case shows that malignant transformation is possible in H-HCA. We present our preoperative decision-making process, as well as the role of imaging techniques in this rare case.

8.
Ann Surg ; 272(6): 919-924, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33021367

RESUMO

OBJECTIVE: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms. SUMMARY OF BACKGROUND DATA: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown. METHODS: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia. RESULTS: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence. CONCLUSIONS: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures.


Assuntos
Infecções Assintomáticas , COVID-19/diagnóstico , Tratamento de Emergência , Programas de Rastreamento/estatística & dados numéricos , Cuidados Pré-Operatórios/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Procedimentos Cirúrgicos Operatórios , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Procedimentos Cirúrgicos Eletivos , Humanos , Estudos Retrospectivos
9.
Environ Sci Technol ; 54(7): 4180-4189, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32142607

RESUMO

The threat posed by plastic pollution to marine ecosystems and human health is under increasing scrutiny. Much of the macro- and microplastic in the ocean ends up on the seafloor, with some of the highest concentrations reported in submarine canyons that intersect the continental shelf and directly connect to terrestrial plastic sources. Gravity-driven avalanches, known as turbidity currents, are the primary process for delivering terrestrial sediment and organic carbon to the deep sea through submarine canyons. However, the ability of turbidity currents to transport and bury plastics is essentially unstudied. Using flume experiments, we investigate how turbidity currents transport microplastics, and their role in differential burial of microplastic fragments and fibers. We show that microplastic fragments become relatively concentrated within the base of turbidity currents, whereas fibers are more homogeneously distributed throughout the flow. Surprisingly, the resultant deposits show an opposing trend, as they are enriched with fibers, rather than fragments. We explain this apparent contradiction by a depositional mechanism whereby fibers are preferentially removed from suspension and buried in the deposits as they are trapped between settling sand-grains. Our results suggest that turbidity currents potentially distribute and bury large quantities of microplastics in seafloor sediments.


Assuntos
Plásticos , Poluentes Químicos da Água , Ecossistema , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Microplásticos
10.
Environ Toxicol Chem ; 37(4): 1024-1031, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29240259

RESUMO

Comprehensive experimental quantification and mapping of the aggregation and dispersion state of engineered nanoparticles (NPs) in the presence of humic substances is a great challenge. Dissipative particle dynamic (DPD) simulation was adopted to investigate the aggregation and dispersion mechanisms of NPs in the presence of a humic substance analog. Twelve different types of NPs including 2 metal-based NPs, 7 metal oxide-based NPs, and 3 carbon-based NPs in pure water (pH 3.0) and algae medium (pH 8.0) in the presence of a humic substance analogy were selected for experimental verification of the DPD simulation results. In agreement with results obtained with dynamic light scattering and phase analysis light scattering techniques, the simulations demonstrated that the presence of humic substances reduced the aggregation extent of the NPs. The DPD simulations showed that the stability and dispersity of the NPs increased first, and then decreased with increasing concentrations of humic substances. Moreover, there existed a concentration of humic substances where the NPs became more stable and more dispersed, which was experimentally verified in the case of all the NPs in the pure water and in the algae medium. Furthermore, theory and simulation indicate that both hydrophobic and hydrogen interaction play an important role in controlling the formation of NP aggregates in the presence of humic substances. Electrostatic interaction and steric repulsion are the main mechanisms underlying the effects of humic substances on the aqueous dispersion stability of NPs. Environ Toxicol Chem 2018;37:1024-1031. © 2017 SETAC.


Assuntos
Simulação por Computador , Substâncias Húmicas/análise , Nanopartículas/química , Nanotecnologia , Água/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Eletricidade Estática
11.
ACS Nano ; 11(10): 9574-9593, 2017 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-28933820

RESUMO

The terms "Safe innovation" and "Safe(r)-by-design" are currently popular in the field of nanotechnology. These terms are used to describe approaches that advocate the consideration of safety aspects already at an early stage of the innovation process of (nano)materials and nanoenabled products. Here, we investigate the possibilities of considering safety aspects during various stages of the innovation process of graphene, outlining what information is already available for assessing potential hazard, exposure, and risks. In addition, we recommend further steps to be taken by various stakeholders to promote the safe production and safe use of graphene.

12.
Environ Pollut ; 220(Pt A): 540-548, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27743792

RESUMO

Riverine transport to the marine environment is an important pathway for microplastic. However, information on fate and transport of nano- and microplastic in freshwater systems is lacking. Here we present scenario studies on the fate and transport of nano-to millimetre sized spherical particles like microbeads (100 nm-10 mm) with a state of the art spatiotemporally resolved hydrological model. The model accounts for advective transport, homo- and heteroaggregation, sedimentation-resuspension, polymer degradation, presence of biofilm and burial. Literature data were used to parameterize the model and additionally the attachment efficiency for heteroaggregation was determined experimentally. The attachment efficiency ranged from 0.004 to 0.2 for 70 nm and 1050 nm polystyrene particles aggregating with kaolin or bentonite clays in natural freshwater. Modeled effects of polymer density (1-1.5 kg/L) and biofilm formation were not large, due to the fact that variations in polymer density are largely overwhelmed by excess mass of suspended solids that form heteroaggregates with microplastic. Particle size had a dramatic effect on the modeled fate and retention of microplastic and on the positioning of the accumulation hot spots in the sediment along the river. Remarkably, retention was lowest (18-25%) for intermediate sized particles of about 5 µm, which implies that the smaller submicron particles as well as larger micro- and millimetre sized plastic are preferentially retained. Our results suggest that river hydrodynamics affect microplastic size distributions with profound implications for emissions to marine systems.


Assuntos
Hidrodinâmica , Nanoestruturas/análise , Tamanho da Partícula , Plásticos/análise , Poliestirenos/análise , Rios/química , Poluentes Químicos da Água/análise , Água Doce/química , Sedimentos Geológicos , Modelos Teóricos , Polímeros/análise
13.
Nat Commun ; 7: 10886, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26996440

RESUMO

Submarine channels are ubiquitous on the seafloor and their inception and evolution is a result of dynamic interaction between turbidity currents and the evolving seafloor. However, the morphodynamic links between channel inception and flow dynamics have not yet been monitored in experiments and only in one instance on the modern seafloor. Previous experimental flows did not show channel inception, because flow conditions were not appropriately scaled to sustain suspended sediment transport. Here we introduce and apply new scaling constraints for similarity between natural and experimental turbidity currents. The scaled currents initiate a leveed channel from an initially featureless slope. Channelization commences with deposition of levees in some slope segments and erosion of a conduit in other segments. Channel relief and flow confinement increase progressively during subsequent flows. This morphodynamic evolution determines the architecture of submarine channel deposits in the stratigraphic record and efficiency of sediment bypass to the basin floor.

15.
Chem Sci ; 7(7): 4308-4317, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30155077

RESUMO

Magnetic resonance imaging (MRI) is a preferred technique for noninvasively monitoring the fate of implanted cells, such as stem cells and immune cells in vivo. Cellular MRI requires contrast agents (CAs) to label the cells of interest. Despite promising progress made in this emerging field, highly sensitive, stable and biocompatible T1 CAs with high cell permeability and specificity remains an unmet challenge. To address this need, a novel MnIII-porphyrin, MnAMP was designed and synthesized based on the modification of MnIIItetra(carboxy-porphyrin) (MnTCP), a small and highly stable non-Gd extracellular CA with good biocompatibility and high T1 relaxivity (r1 = 7.9 mM-1 s-1) at clinical field of 3 Tesla (T). Cell permeability was achieved by masking the polar carboxylates of MnTCP with acetoxymethyl-ester (AM) groups, which are susceptible to hydrolysis by intracellular esterases. The enzymatic cleavage of AM groups led to disaggregation of the hydrophobic MnAMP, releasing activated MnTCP with significant increase in T1 relaxivity. Cell uptake of MnAMP is highly efficient as tested on two non-phagocytic human cell lines with no side effects observed on cell viability. MRI of labeled cells exhibited significant contrast enhancement with a short T1 of 161 ms at 3 T, even though a relatively low concentration of MnAMP and short incubation time was applied for cell labeling. Overall, MnAMP is among the most efficient T1 cell labeling agents developed for cellular MRI.

16.
Water Res ; 80: 200-8, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26001284

RESUMO

Site specific exposure assessments for engineered nanoparticles (ENPs) require spatially explicit fate models, which however are not yet available. Here we present an ENP fate model (NanoDUFLOW) that links ENP specific process descriptions to a spatially explicit hydrological model. The link enables the realistic modelling of feedbacks between local flow conditions and ENP fate processes, such as homo- and heteroaggregation, resuspension and sedimentation. Spatially explicit simulations using five size classes of ENPs and five size classes of natural solids showed how ENP sediment contamination 'hot spots' and ENP speciation can be predicted as a function of place and time. For the catchment modelled, neglect of spatial heterogeneity caused relatively small differences in ENP retention. However, simplification of the number of size classes to one average class, resulted in up to 3.3 times lower values of retention compared to scenarios that used detailed size distributions. Local concentrations in sediment were underestimated up to 20 fold upon simplification of spatial heterogeneity or particle size distribution. We conclude that spatial heterogeneity should not be neglected when assessing the risks of ENPs.


Assuntos
Algoritmos , Água Doce/química , Nanopartículas Metálicas/química , Modelos Teóricos , Rios/química , Cério/química , Sedimentos Geológicos/química , Hidrodinâmica , Tamanho da Partícula , Prata/química
17.
Environ Toxicol Chem ; 34(6): 1239-45, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25683234

RESUMO

The present study investigated how humic substances (HS) modify the aquatic toxicity of silver nanoparticles (AgNPs) as these particles agglomerate in water and interact with HS. An alga species (Raphidocelis subcapitata), a cladoceran species (Chydorus sphaericus), and a freshwater fish larva (Danio rerio), representing organisms of different trophic levels, were exposed to colloids of the polyvinylpyrrolidone-coated AgNPs in the presence and absence of HS. Results show that the presence of HS alleviated the aquatic toxicity of the AgNP colloids to all the organisms in a dose-dependent manner. The particle size distribution of the AgNPs' colloidal particles shifted to lower values due to the presence of HS, implying that the decrease in the toxicity of the AgNP colloids cannot be explained by the variation of agglomeration size. The surface charge of the AgNPs was found to be more negative in the presence of high concentrations of HS, suggesting an electrostatic barrier by which HS might limit interactions between particles and algae cells; indeed, this effect reduced the algae toxicity. Observations on silver ions (Ag(+)) release show that HS inhibit AgNP dissolution, depending on the concentrations of HS. When toxic effects were expressed as a function of each Ag-species, toxicity of the free Ag(+) was found to be much higher than that of the agglomerated particles.


Assuntos
Clorófitas/fisiologia , Cladocera/fisiologia , Substâncias Húmicas , Nanopartículas Metálicas/toxicidade , Povidona/toxicidade , Prata/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Coloides , Relação Dose-Resposta a Droga , Tamanho da Partícula , Prata/metabolismo
18.
PLoS One ; 9(8): e102843, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25101835

RESUMO

Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core. We determined how islet remodeling in autoimmune diabetes compares to streptozotocin (STZ)-induced diabetes. Islet cell mass, proliferation, and immune cell infiltration in pancreas sections from diabetic NOD mice and mice with STZ-induced diabetes was assessed using quantitative image analysis. Serial sections were stained for various beta-cell markers and Ngn3, typically restricted to embryonic tissue, was only upregulated in diabetic NOD mouse islets. Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state. Total pancreatic alpha-cell mass did not change as autoimmune diabetes developed in NOD mice despite the proportion of islet area comprised of alpha- and delta-cells increased. By contrast, alpha- and delta-cell mass was increased in mice with STZ-induced diabetes. Serum levels of glucagon reflected these changes in alpha-cell mass: glucagon levels remained constant in NOD mice over time but increased significantly in STZ-induced diabetes. Increased serum GLP-1 levels were found in both models of diabetes, likely due to alpha-cell expression of prohormone convertase 1/3. Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation. Hence, the inflammatory milieu in NOD mouse islets may restrict alpha-cell expansion highlighting important differences between these two diabetes models and raising the possibility that increased alpha-cell mass might contribute to the hyperglycemia observed in the STZ model.


Assuntos
Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , Ilhotas Pancreáticas/patologia , Animais , Glicemia , Proliferação de Células , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Feminino , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Células Secretoras de Glucagon/patologia , Imuno-Histoquímica , Insulina/sangue , Insulina/metabolismo , Insulina/farmacologia , Células Secretoras de Insulina/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Somatostatina/metabolismo
19.
Water Res ; 62: 193-201, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24956601

RESUMO

Parameters and simplified model approaches for describing the fate of engineered nanoparticles (ENPs) are crucial to advance the risk assessment of these materials. Sedimentation behavior of ENPs in natural waters has been shown to follow apparent first order behavior, a 'black box' phenomenon that is insufficiently understood and therefore of limited applicability. Here we use a detailed Smoluchowski-Stokes model that accounts for homo- and heteroaggregation and sedimentation of ENPs and natural colloids (NCs), to simulate and interpret experimental ENP aggregation-sedimentation data. The model adequately simulated the observed time and initial concentration dependence of CeO2 settling data, and also predicted the conditions for aggregation rate-limitations of overall removal. Heteroaggregation with natural colloids was identified as the dominating removal process. Finally, the empirical apparent first order model data were calibrated against the mechanistic Smoluchowski-Stokes model simulation data, showing excellent fits for a range of NC initial concentrations. Using first order removal rates thus can be considered a valid and informed approximation when modeling ENP fate in the aquatic environment.


Assuntos
Coloides/química , Meio Ambiente , Modelos Teóricos , Nanopartículas/química , Cério/química , Nanotecnologia , Compostos Orgânicos/química
20.
Environ Toxicol Chem ; 33(8): 1766-73, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24753080

RESUMO

Sedimentation of engineered nanoparticles (ENPs) has been studied mainly in artificial media and stagnant systems mimicking natural waters. This neglects the role of turbulence and heteroaggregation with sediment. The authors studied the apparent sedimentation rates of selected ENPs (cerium dioxide [CeO2 ], polyvinylpyrrolidone-capped silver [PVP-Ag], and silica-coated silver [SiO2 -Ag]) in agitated sediment-water systems resembling fresh, estuarine, and marine waters. Experiments were designed to mimic low energy and periodically resuspended sediment water systems (14 d), followed by a long-term aging, resuspension, and settling phase (6 months), as would occur in receiving shallow lakes. The ENPs in systems with periodical resuspension of sediment were removed with sedimentation rates between 0.14 m/d and 0.50 m/d. The sedimentation rates did not vary much among ENP type, salinity, and aging time, which is attributed to the capture of ENPs in sediment flocks. The sedimentation rates were 1 to 2 orders of magnitude higher than those reported for aggregation-sedimentation in stagnant systems without suspended sediment. Heteroaggregation rates were estimated and ranged between 0.151 L/mg/d and 0.547 L/mg/d, which is up to 29 times higher than those reported for natural colloids under quiescent settling conditions. The authors conclude that rapid scavenging and sedimentation drives removal of ENPs from the water column.


Assuntos
Sedimentos Geológicos/química , Nanopartículas/química , Cério/química , Engenharia , Cinética , Povidona/química , Salinidade , Dióxido de Silício/química , Prata/química , Suspensões , Água/química
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