An introduction to the analysis of shotgun metagenomic data. Front Plant Sci ; 5 : 1— Surface area of the digestive tract—revisited. Scand J Gastroenterol ; 49 : — A human gut microbial gene catalogue established by metagenomic sequencing. Nature ; : 59— Gut biogeography of the bacterial microbiota. Nat Rev Micro ; 14 : 20— High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals.
Gut Microbes ; 6 : — The Mouse Intestinal Bacterial Collection miBC provides host-specific insight into cultured diversity and functional potential of the gut microbiota. Nat Microbiol ; 1 : Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design. Extensive strain-level copy-number variation across human gut microbiome species. Cell ; : — Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography.
Ann Am Thorac Soc ; 12 : — Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. Topographical continuity of bacterial populations in the healthy human respiratory tract. The internal surface area of the adult human lung. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. The lung tissue microbiome in chronic obstructive pulmonary disease. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota.
The placenta harbors a unique microbiome. Sci Transl Med ; 6 : ra The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants' life: a systematic review. BMC Gastroenterol ; 16 : 1— Early-life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota.
Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old Infants. JAMA Pediatr ; : — Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol ; 80 : — The long-term stability of the human gut microbiota. Science ; : 1—9. Host genetic variation impacts microbiome composition across human body sites. Genome Biol ; 16 : Identifying personal microbiomes using metagenomic codes.
Genomic characterization of the uncultured Bacteroidales family S inhabiting the guts of homeothermic animals.
Microbiome ; 4 : Design, synthesis, and structure-activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Microbial shifts in the aging mouse gut. Microbiome ; 2 : 1— Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front Cell Infect Microbiol ; 5 : 1— Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with irritable bowel syndrome.
Aliment Pharmacol Ther ; 42 : — The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med ; 8 : 1— Diet rapidly and reproducibly alters the human gut microbiome. Diet-induced extinctions in the gut microbiota compound over generations. Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome. Sci Rep ; 6 : 1—9. High purity galacto-oligosaccharides enhance specific Bifidobacterium species and their metabolic activity in the mouse gut microbiome. Benef Microbes ; 7 : — Cell Metabol ; 22 : — For both formats the functionality available will depend on how you access the ebook via Bookshelf Online in your browser or via the Bookshelf app on your PC or mobile device.
Stay on CRCPress. Exclusive web offer for individuals on all book. Preview this Book. Add to Wish List. Close Preview. Toggle navigation Additional Book Information. Description Table of Contents. Summary Written by an expanded team of leading international scientists, the second edition thoroughly investigates research and therapies for managing adverse physiological effects of air-borne particles on the respiratory tract. Request an e-inspection copy. Share this Title.
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Diesel exhaust inhalation increases thrombus formation in man Eur. Lucking, Andrew J. Oxford University Press. Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction MI. The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and thrombus formation in men.
In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dil. Thrombus formation, coagulation, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. This increased thrombogenicity was seen at 2 and 6 h, using two different diesel engines and fuels.
Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis Circulation , , — DOI: Mills, Nicholas L. Background- Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction.
The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. Methods and Results- In a double-blind, randomized, cross-over study, 30 healthy men were exposed to dild. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air.
Conclusions- At levels encountered in an urban environment, inhalation of dil. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model JAMA , , — DOI: American Medical Association.
Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be detd. The objective was to test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concns. Between July 21,, and Jan. Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes were found. In the high-fat chow group, the mean SD composite plaque area of PM2.
FA was Lipid content in the aortic arch measured by oil red-O staining revealed a 1. FA Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2. Mice fed high-fat chow and exposed to PM2.
Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice Part. Fibre Toxicol. Miller, Mark R. BioMed Central Ltd. Objective: Diesel exhaust particulate DEP , a major component of urban air pollution, has been linked to atherogenesis and pptn. Atherosclerotic burden was assessed by en-face staining of the thoracic aorta and histol. These changes were assocd. Conclusions: Increased atherosclerosis is caused by the particulate component of diesel exhaust producing advanced plaques with a potentially more vulnerable phenotype.
These results are consistent with the suggestion that removal of the particulate component would reduce the adverse cardiovascular effects of diesel exhaust. Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure Part. Particle and fibre toxicology , 2 , 10 ISSN:. This review considers the molecular toxicology of combustion-derived nanoparticles CDNP following inhalation exposure. CDNP originate from a number of sources and in this review we consider diesel soot, welding fume, carbon black and coal fly ash. A substantial literature demonstrates that these pose a hazard to the lungs through their potential to cause oxidative stress, inflammation and cancer; they also have the potential to redistribute to other organs following pulmonary deposition.
These different CDNP show considerable heterogeneity in composition and solubility, meaning that oxidative stress may originate from different components depending on the particle under consideration. Key CDNP-associated properties of large surface area and the presence of metals and organics all have the potential to produce oxidative stress.
CDNP may also exert genotoxic effects, depending on their composition. CDNP and their components also have the potential to translocate to the brain and also the blood, and thereby reach other targets such as the cardiovascular system, spleen and liver. CDNP therefore can be seen as a group of particulate toxins unified by a common mechanism of injury and properties of translocation which have the potential to mediate a range of adverse effects in the lungs and other organs and warrant further research.
From particles to patients: oxidative stress and the cardiovascular effects of air pollution Future Cardiol. Air pollution, esp. The one consistent observation that links the pulmonary and cardiovascular effects of inhaled PM is oxidative stress. This article examines the evidence for the role of oxidative stress in the cardiovascular effects of air pollution, beginning with observations from epidemiol. Particular emphasis is placed on the vascular and atherosclerotic effects of urban air pollution and diesel exhaust emissions as rich sources of environmental ultrafine particles.
Particulate air pollution and acute health effects Lancet , , — DOI: Epidemiological studies have consistently shown an association between particulate air pollution and not only exacerbations of illness in people with respiratory disease but also rises in the numbers of deaths from cardiovascular and respiratory disease among older people. Meta-analyses of these studies indicate that the associations are unlikely to be explained by any confounder, and suggest that they represent cause and effect.
We suggest that such ultra-fine particles are able to provoke alveolar inflammation, with release of mediators capable, in susceptible individuals, of causing exacerbations of lung disease and of increasing blood coagulability, thus also explaining the observed increases in cardiovascular deaths associated with urban pollution episodes. This hypothesis is testable both experimentally and epidemiologically. Adverse cardiovascular effects of air pollution Nat. Mills et al. Understanding the mediators and mechanisms will enable the development of strategies to reduce the impact of air pollution on cardiovascular disease.
Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular disease in urban communities. Acute exposure has been linked to a range of adverse cardiovascular events including hospital admissions with angina, myocardial infarction, and heart failure. Long-term exposure increases an individual's lifetime risk of death from coronary heart disease.
The main arbiter of these adverse health effects seems to be combustion-derived nanoparticles that incorporate reactive org. Inhalation of this particulate matter leads to pulmonary inflammation with secondary systemic effects or, after translocation from the lung into the circulation, to direct toxic cardiovascular effects. Through the induction of cellular oxidative stress and proinflammatory pathways, particulate matter augments the development and progression of atherosclerosis via detrimental effects on platelets, vascular tissue, and the myocardium.
These effects seem to underpin the atherothrombotic consequences of acute and chronic exposure to air pollution. An increased understanding of the mediators and mechanisms of these processes is necessary if we are to develop strategies to protect individuals at risk and reduce the effect of air pollution on cardiovascular disease.
Nanotoxicology , 9 8 , ISSN:. Moreover, the biological effects of such low levels of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following translocation from the lungs.
Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. This study characterizes the subtle systemic effects that occur in liver and heart tissues following pulmonary exposure and low levels of translocation of nano-TiO2 from lungs.
Prior lung inflammation impacts on body distribution of gold nanoparticles BioMed Res. It is, therefore, critical to evaluate exposure to Au-nanomaterials with varied preexisting health status. Metal contents were analyzed in different organs by inductively coupled plasma-mass spectrometry ICP-MS. Significantly higher concentrations of Au were detected in heart and thymus of healthy animals, whereas higher concentrations of Au NPs were observed in spleen in LPS-primed animals. Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model Part.
Particle and fibre toxicology , 4 , 9 ISSN:. Little is known, however, about the dependence of particle size or material on translocation characteristics, inflammatory response and intracellular localization. RESULTS: Using a triple cell co-culture model of the human airway wall composed of epithelial cells, macrophages and dendritic cells we quantified the entering of fine 1 mum and nano-sized 0.
The number distribution of particles within the cell types was significantly different between fine and nano-sized particles suggesting different translocation characteristics. Analysis of the intracellular localization of gold 0. Titanium dioxide nanoparticles were detected as single particles without membranes as well as in membrane-bound agglomerations.
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Gold nanoparticles were found inside the cells as free particles only. The potential of the different particle types different sizes and different materials to induce a cellular response was determined by measurements of the tumour necrosis factor-alpha in the supernatants.
We measured a fold increase of tumour necrosis factor-alpha in the supernatants after applying 1 mum polystyrene particles, gold nanoparticles, but not with polystyrene and titanium dioxide nanoparticles. Energy filtering transmission electron microscopy showed that the intracellular localization of nanoparticles depends on the particle material.
Both particle size and material affect the cellular responses to particle exposure as measured by the generation of tumour necrosis factor-alpha. The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung Part. Particle and fibre toxicology , 2 , 3 ISSN:.
The objective of this study was to evaluate the role of the endothelial barrier in the translocation of inhaled UFP from the lung into circulation. Particle inhalation was done under following treatments: i control perfusion, ii histamine 1 microM in perfusate, iii luminal histamine instillation 1 mM , and iv luminal instillation of H2O2. Particle translocation to the perfusate was assessed by the radioactivity of Ir isotope. In addition to light microscopic morphological evaluation of fixed lungs, alkaline phosphatase AKP and angiotensin converting enzyme ACE in perfusate were measured to assess epithelial and endothelial integrity.
No translocation of Ir particles at negative pressure inhalation was detected in control IPL, but lungs pretreated with histamine 1 microM in the perfusate or with luminal H2O2 0. Although the kinetics of particle translocation were different from permeability for 99mTc-DTPA, the pretreatments H2O2, vascular histamine caused similar changes in the translocation of particles and soluble mediator. Increased translocation through epithelium and endothelium with a lag time of one hour occurred in the absence of epithelial and endothelial damage.
Conditions that affect this barrier function such as inflammation may affect translocation of NP. Passage of inhaled particles into the blood circulation in humans Circulation , , — DOI: Nemmar, A. Pollution by particulates has been consistently assocd. However, the mechanisms responsible for these effects are not well-elucidated. Radioactivity was detected in blood already at 1 min, reached a max. Thin layer chromatog. Gamma camera images showed substantial radioactivity over the liver and other areas of the body. The authors conclude that inhaled 99mTc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extra-pulmonary effects of air pollution.
Deposition, retention, and translocation of ultrafine particles from the central airways and lung periphery Am. Care Med. American journal of respiratory and critical care medicine , 4 , ISSN:. These particles may accumulate and present a health hazard because of their high surface area. METHODS: Using a bolus inhalation technique, particle deposition was targeted either to the airways or to the lung periphery, and retention, clearance, and translocation were measured using retained radiotracer imaging.
Cumulative 99m Tc activity in urine at 24 hours was 1. The small amount of clearance could be attributed to leaching of the 99m Tc label, suggesting negligible particle clearance. Radiolabel activity did not accumulate in the liver. Repeated exposure may result in significant pulmonary accumulation of ultrafine particles.
Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low J. Kreyling, W. Recently it was speculated that ultrafine particles may translocate from deposition sites in the lungs to systemic circulation. This could lead to accumulation and potentially adverse reactions in crit. Ultrafine Ir radio-labeled iridium particles 15 and 80 nm count median diam.
After exposure, excreta were collected quant. At time points ranging from 6 h to 7 d, rats were sacrificed, and a complete balance of Ir activity retained in the body and cleared by excretion was detd. Thoracic deposition fractions of inhaled and nm Ir particles were 0.
Both batches of ultrafine iridium particles proved to be insol. During wk 1 after inhalation particles were predominantly cleared via airways into the gastrointestinal tract and feces. This cleared fraction includes particles deposited in the alveolar region. The translocated fraction of the nm particles was about an order of magnitude less than that of nm particles. In addnl. They confirmed the low soly. This study indicates that only a rather small fraction of ultrafine iridium particles has access from peripheral lungs to systemic circulation and extrapulmonary organs.
Therefore, the hypothesis that systemic access of ultrafine insol. Rapid translocation of nanoparticles from the lung airspaces to the body Nat. Nano-size particles show promise for pulmonary drug delivery, yet their behavior after deposition in the lung remains poorly understood. The authors demonstrate that nanoparticles with hydrodynamic diam. The authors discuss the importance of these findings for drug delivery, air pollution and carcinogenesis. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats J.
Studies with i. Measuring translocation of inhaled ultrafine particles to extrapulmonary organs via the blood compartment is hampered by methodol. The objective of our pilot study was to det. We generated ultrafine 13C particles as an aerosol with count median diams. Nine Fischer rats were exposed to these particles for 6 h. Six unexposed rats served as controls.
Lung lobes, liver, heart, brain, olfactory bulb, and kidney were excised, homogenized, and freeze-dried for anal. The 13C retained in the lung at 0. Normalized to exposure concn. Significant amts. No significant increase in 13C was detected in the other organs which were examd. These results demonstrate effective translocation of ultrafine elemental carbon particles to the liver by 1 d after inhalation exposure.
Translocation pathways include direct input into the blood compartment from ultrafine carbon particles deposited throughout the respiratory tract. However, since predictive particle deposition models indicate that respiratory tract deposits alone may not fully account for the hepatic 13C burden, input from ultrafine particles present in the GI tract needs to be considered as well. Such translocation to blood and extrapulmonary tissues may well be different between ultrafine carbon and other insol. Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration Eur.
Elsevier B. Gold nanoparticles GNP provide many opportunities in imaging, diagnostics, and therapies of nanomedicine. Hence, their biokinetics in the body are prerequisites for specific tailoring of nanomedicinal applications and for a comprehensive risk assessment. We administered Au-radio-labeled monodisperse, neg. After 24 h, the biodistribution of the GNP was quant.
The size and surface charge of GNP strongly det. In contrast, there was little size-dependent accumulation of nm GNP in most other organs. However, for GNP between 1. The differently charged 2. We conclude that the alterations of accumulation in the various organs and tissues, depending on GNP size and surface charge, are mediated by dynamic protein binding and exchange. A better understanding of these mechanisms will improve drug delivery and dose ests.
Do inhaled carbon nanoparticles translocate directly into the circulation in humans? It has been suggested that the nanoparticulate component of PM 10 is capable of translocating into the circulation with the potential for direct effects on the vasculature. Technegas particles were nm in diameter and aggregated to a median particle diameter of approximately nm. Radioactivity was immediately detected in blood, with levels increasing over 60 min.
Thin-layer chromatography of whole blood identified a species that moved with the solvent front, corresponding to unbound 99m Tc-pertechnetate, which was excreted in urine. There was no evidence of particle-bound 99m Tc at the origin. In contrast to previous published studies, thin-layer chromatography did not support the hypothesis that inhaled Technegas carbon nanoparticles pass directly from the lungs into the systemic circulation. Gold nanoparticles: a revival in precious metal administration to patients Nano Lett.
American Chemical Society. Gold has been used as a therapeutic agent to treat a wide variety of rheumatic diseases including psoriatic arthritis, juvenile arthritis, and discoid lupus erythematosus. Although the use of gold has been largely superseded by newer drugs, gold nanoparticles are being used effectively in lab. For these reasons, gold nanoparticles are therefore well placed to enter mainstream clin. Hence, the present review summarizes the chem. The beneficial attributes of gold nanoparticles, such as their ease of synthesis, functionalization, and shape control are also highlighted demonstrating why gold nanoparticles are an attractive target for further development and optimization.
The importance of controlling the size and shape of gold nanoparticles to minimize any potential toxic side effects is also discussed. Trace Elem. Elsevier GmbH. The blood samples were collected in lithium heparin monovettes developed for trace metal detn. For sample introduction into the ICP, the blood samples were dild. The method validation of our developed routine method is described for all 37 elements and results about internal and external quality assurance are discussed. Information on exposure conditions of all human subjects were collected by questionnaire-based interviews, including smoking habits, seafood consumption and the type of dental alloys in the teeth.
Mean values, geometric mean values, ranges and selected percentiles of all elemental concns. Biodistribution of 1. The NP accumulation pattern in the secondary-target organs differs strongly from those seen after direct i. From this, it is hypothesized that NPs interact dynamically with proteins and cells, which dets. Distribution pattern of inhaled ultrafine gold particles in the rat lung Inhalation Toxicol. Takenaka, S. The role of alveolar macrophages in the fate of ultrafine particles in the lung was investigated.
Male Wistar-Kyoto rats were exposed to ultrafine gold particles, generated by a spark generator, for 6 h at a concn. Up to 7 days, the animals were serially sacrificed, and lavaged cells and lung tissues were examd. The gold concn. Gold particles used were spherical and electron dense with diams. The particles were individual or slightly agglomerated.
By inductively coupled plasma-mass spectrometry anal. A low but significant increase of gold 0. Small vesicles contg. In the alveolar septum, the gold particles were enclosed in vesicles obsd. These results indicate that inhaled ultrafine gold particles in alveolar macrophages and type I epithelial cells are processed by endocytotic pathways, though the uptake of the gold particles by alveolar macrophages is limited. To a low degree, systemic particle translocation took place. Translocation of gold nanoparticles across the lung epithelial tissue barrier: Combining in vitro and in silico methods to substitute in vivo experiments Part.
Particle and fibre toxicology , 12 , 18 ISSN:. Thus great efforts are currently being made to determine adverse health effects associated with inhalation of NPs. However, to date very little is known about factors that determine the pulmonary translocation of NPs and their subsequent distribution to secondary organs. In a first step, alveolar epithelial cellular monolayers CMLs at the air-liquid interface ALI were exposed to aerosolized NPs to determine their translocation kinetics across the epithelial tissue barrier.
Then, in a second step, the distribution to secondary organs was predicted with a physiologically based pharmacokinetic PBPK model. Monodisperse, spherical, well-characterized, negatively charged gold nanoparticles AuNP were used as model NPs. Furthermore, to obtain a comprehensive picture of the translocation kinetics in different species, human A and mouse MLE alveolar epithelial CMLs were exposed to ionic gold and to various doses i. Furthermore, supplementing the A CML with two immune cells, i. Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs Inhalation Toxicol.
Semmler, M. Recently it was speculated that ultrafine particles UFP may translocate from deposition sites in the lungs to systemic circulation and whether long-term clearance differs between ultrafine and micrometer-sized particles. The authors have studied lung retention and clearance kinetics in 12 healthy male adult WKY rats up to 6 mo after an inhalation of Ir-radiolabeled, insol.
Whole-body retention was followed by external gamma counting, and particle clearance kinetics were detd. Four rats each were sacrificed after 3 wk and 2 and 6 mo; all organs as well as tissues and the carcass were radioanalyzed to balance the entire deposited radioactivity of the particles. Extrapulmonary particle uptake did not continue to increase but decreased with time in liver, spleen, heart, and brain when compared to previous data obtained during the first 7 days after inhalation W.
Kreyling et al. The UFP long-term lung retention derived from whole-body measurements was comparable to previously reported data using insol. Snipes et al. Bailey et al. Efficient elimination of inhaled nanoparticles from the alveolar region: evidence for interstitial uptake and subsequent reentrainment onto airways epithelium Environ. Health Perspect. We studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and bronchoalveolar lavage BAL measurements in healthy adult Wistar Kyoto WKY rats at various times over 6 mo after administration of a single to min intratracheal inhalation of iridium Ir -radiolabeled NPs.
A complete Ir balance of all organs, tissues, excretion, remaining carcass, and BAL was performed at each time point. After 3 wk, lavageable NP fractions decreased to 0. This is in stark contrast to the AM-assocd. These particles remained const. There is a strong size-selective difference in particle immobilization. Furthermore, AM-mediated NP transport to the larynx originates not only from the NP fraction retained on the epithelium but also from NPs being reentrained from the interstitium to the luminal side of epithelium.
We conclude that NPs are much less phagocytized by AMs than large particles but are effectively removed from the lung surface into the interstitium. Even from these interstitial sites, they undergo AM-mediated long-term NP clearance to the larynx. Translocation of particles deposited in the respiratory system: a systematic review and statistical analysis Environ. Health Prev. Environmental health and preventive medicine , 17 4 , ISSN:. Many epidemiological studies have demonstrated that ambient particulate matter poses consistent risks for respiratory and cardiovascular disorders.
The translocation of inhaled particles is one hypothesis that could explain such systemic effects. The objectives of this study were to conduct a systematic review of previous reports on particle translocation from the respiratory system and to discuss factors important for translocation. A PubMed search was conducted in August for the period from with four main keyword domains particle, translocation, detection site, and exposure route.
The systematic review identified 61 original articles written in English that met the specified criteria i. Categorical regression analysis was performed with the site of particle detection as the objective variable, and particle size, particle material, animal species, and exposure route as the explanatory variables. All explanatory variables showed statistically significant effects. The effects for particle size and particle material were large, while the effects for animal species and exposure route were relatively small.
However, these results should be considered within the context of several limitations, such as deficiency of information. The effect of primary particle size on biodistribution of inhaled gold nano-agglomerates Biomaterials , 34 , — DOI: Balasubramanian, Suresh K.
Elsevier Ltd. Airborne engineered nanoparticles undergo agglomeration, and careful distinction must be made between primary and agglomerate size of particles, when assessing their health effects. This study compares the effects on rats undergoing day inhalation exposure to airborne agglomerates of gold nanoparticles AuNPs of similar size distribution and no. Inhalation of agglomerates contg.
Macrophage mediated escalation followed by fecal excretion is the major pathway of clearing inhaled AuNPs in the lungs. Microarray analyses of the hippocampus showed mostly downregulated genes, related to the cytoskeleton and neurite outgrowth. Together, results in this study indicate disintegration of nanosized agglomerates after inhalation and show impact of primary size of particles on subsequent biodistribution.
Biodistribution of gold nanoparticles in mouse lung following intratracheal instillation Chem. The nanoparticles were traced by autometallography AMG at both ultrastructural and light microscopic levels. The liver is the major site of deposition of circulating gold nanoparticles. Therefore the degree of translocation was determined by the hepatic deposition of gold. Mice were instilled with 5 intratracheal doses of gold nanoparticles distributed over a period of 3 weeks and were killed 24 h after the last dose. One group of mice were given a single intratracheal dose and were killed after 1 h.
In mice instilled treated repeatedly during 3 weeks, the load was substantial. In mice given repeated instillations of 2 nm gold nanoparticles, 1. With the 40 nm gold, no gold was detected in the liver detection level 2 ng, 0. No gold was detected in any liver of mice instilled with nm gold detection level 2 ng, 0. Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size ACS Nano , 8 , — DOI: Kreyling, Wolfgang G.
Gold nanoparticles AuNP provide many opportunities in imaging, diagnostics, and therapy in nanomedicine. For the assessment of AuNP biokinetics, we intratracheally instilled into rats a suite of Au-radio-labeled monodisperse, well-characterized, neg. At 1, 3, and 24 h, the biodistribution of the AuNP was quant.
Our study shows that as AuNP get smaller, they are more likely to cross the air-blood barrier ABB depending strongly on the inverse diam. So, 1. Only renal filtration, retention in blood, and excretion via urine further declined with d-1 of AuNP core. Translocation of 5, 18, and 80 nm AuNP is virtually complete after 1 h, while 1.
Translocation of neg. Our study shows that translocation across the ABB and accumulation and retention in secondary organs and tissues are two distinct processes, both depending specifically on particle characteristics such as SSA and surface charge. Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability J.
Journal of angiogenesis research , 2 , 14 ISSN:. According to the classic small pore theory of microvascular permeability, which was formulated on the basis of the findings of studies on the transcapillary flow rates of various-sized systemically or regionally perfused endogenous macromolecules, transcapillary exchange across the capillary wall takes place through a single population of small pores that are approximately 6 nm in diameter; whereas, according to the dual pore theory of microvascular permeability, which was formulated on the basis of the findings of studies on the accumulation of various-sized systemically or regionally perfused non-endogenous macromolecules in the locoregional tissue lymphatic drainages, transcapillary exchange across the capillary wall also takes place through a separate population of large pores, or capillary leaks, that are between 24 and 60 nm in diameter.
The classification of blood capillary types on the basis of differences in the physiologic upper limits of pore size to transvascular flow highlights the differences in the transcapillary exchange routes for the transvascular transport of endogenous and non-endogenous macromolecules across the capillary walls of different blood capillary types. METHODS: The findings and published data of studies on capillary wall ultrastructure and capillary microvascular permeability to lipid-insoluble endogenous and non-endogenous molecules from the s to date were reviewed.
In this study, the blood capillary types in different tissues and organs were classified on the basis of the physiologic upper limits of pore size to the transvascular flow of lipid-insoluble molecules. Blood capillaries were classified as non-sinusoidal or sinusoidal on the basis of capillary wall basement membrane layer continuity or lack thereof. Non-sinusoidal blood capillaries were further sub-classified as non-fenestrated or fenestrated based on the absence or presence of endothelial cells with fenestrations.
The sinusoidal blood capillaries of the liver, myeloid red bone marrow, and spleen were sub-classified as reticuloendothelial or non-reticuloendothelial based on the phago-endocytic capacity of the endothelial cells. RESULTS: The physiologic upper limit of pore size for transvascular flow across capillary walls of non-sinusoidal non-fenestrated blood capillaries is less than 1 nm for those with interendothelial cell clefts lined with zona occludens junctions i. The physiologic upper limit of pore size for transvascular flow across the capillary walls of non-sinusoidal fenestrated blood capillaries with diaphragmed fenestrae ranges between 6 and 12 nm i.
In the case of the sinusoidal reticuloendothelial blood capillaries of myeloid bone marrow, the transvascular transport of non-endogenous macromolecules larger than 5 nm into the bone marrow interstitial space takes place via reticuloendothelial cell-mediated phago-endocytosis and transvascular release, which is the case for systemic bone marrow imaging agents as large as 60 nm in diameter. Therefore, macromolecules larger than the physiologic upper limits of pore size in the non-sinusoidal blood capillary types generally do not accumulate within the respective tissue interstitial spaces and their lymphatic drainages.
In the case of reticuloendothelial sinusoidal blood capillaries of myeloid bone marrow, however, non-endogenous macromolecules as large as 60 nm in diameter can distribute into the bone marrow interstitial space via the phago-endocytic route, and then subsequently accumulate in the locoregional lymphatic drainages of tissues following absorption into the lymphatic drainage of periosteal fibrous tissues, which is the lymphatic drainage of myeloid bone marrow.
When the ultrastructural basis for transcapillary exchange across the capillary walls of different capillary types is viewed in this light, it becomes evident that the physiologic evidence for the existence of aqueous large pores ranging between 24 and 60 nm in diameter in the capillary walls of blood capillaries, is circumstantial, at best. Renal clearance of quantum dots Nat. The field of nanotechnol. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegrdn. Using i.
Zwitterionic or neutral org. A final hydrodynamic diam. This study provides a foundation for the design and development of biol. In vitro and in vivo interactions of selected nanoparticles with rodent serum proteins and their consequences in biokinetics Beilstein J. Beilstein Journal of Nanotechnology , 5 , , 13 pp. Beilstein-Institut zur Foerderung der Chemischen Wissenschaften. When particles incorporated within a mammalian organism come into contact with body fluids they will bind to sol. This binding process is very complex and highly dynamic due to the plethora of proteins with different affinities and fractions in different body fluids and the large variation of compds.
Interestingly, in the case of nanoparticles NP this protein corona is well suited to provide a guiding vehicle of translocation within body fluids and across membranes. This NP translocation may subsequently lead to accumulation in various organs and tissues and their resp. Because of this unprecedented NP accumulation, potentially adverse biol. Therefore, we studied the interactions and protein binding kinetics of blood serum proteins with a no. Here we show by in vitro incubation tests that the binding capacity of different engineered NP polystyrene, elemental carbon for selected serum proteins depends strongly on the NP size and the properties of engineered surface modifications.
In the following attempt, we studied systematically the effect of the size 5, 15, 80 nm of gold spheres AuNP , surface-modified with the same ionic ligand; as well as 5 nm AuNP with five different surface modifications on the binding to serum proteins by using proteomics analyses. We found that the binding of numerous serum proteins depended strongly on the physicochem. These in vitro results helped us substantially in the interpretation of our numerous in vivo biokinetics studies performed in rodents using the same NP. These had shown that not only the physicochem.
Our in vitro protein binding studies support the notion that the obsd. Protein transport across the lung epithelial barrier Am. Lung Cell. Quantification of extrapulmonary translocation of intratracheal-instilled particles in vivo in rats: effect of lipopolysaccharide Toxicology , , — DOI: Particulate air pollution is assocd. However, important uncertainties remain in the quantification of extrapulmonary translocation of ultrafine particles into blood circulation.
Pulmonary Aerosol Delivery
Therefore, the widely used radioiodinated technique was applied to radiolabel polystyrene particles with an av. The extrapulmonary distribution of these particles 3. Moreover, we have taken into account the possible involvement of pulmonary inflammation in this process.
Rats which received a single intratracheal instillation of free I or a single i.
Lung Biology in Health and Disease
The results indicated that the pulmonary deposition of radioactivity was almost unchanged for both sizes. Only small amts. However, the extent of particle translocation into the blood of the ultrafine size following the pretreatment with lipopolysaccharides was significantly higher from 1. In conclusion, our findings suggest that only a small fraction of intratracheal-instilled ultrafine particles can pass rapidly into systemic circulation, but this translocation is markedly increased following LPS pretreatment.
Thus, pulmonary inflammation seems to play a major role in enhancing the extrapulmonary translocation of particles. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging Circulation , , — DOI: Kooi, M. Toxicity of novel nanosized formulations used in medicine Methods Mol.
While this motivation has driven nanoscience and technol. The application of nanotechnol. This chapter is intended to provide an overview of the toxicity of these therapeutic nanoparticles and to summarize the current state of the field. We begin with background on the sources of exposure to nanoparticles, followed by reviewing different forms of nanosized therapeutic tools as quantum dots, nanoshells, nanocapsules, echogenic bubble, and "nanoshuttles.
We highlight the need for caution during the use and disposal of such manufd. Moreover, different strategies which could be used to minimize or eliminate nanotoxicity were also discussed in detail. Understanding of how to tune size and surface properties to provide safety will permit the creation of new, more effective nanomedicines for systemic use. Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat Part.
Background: There is evidence that nanoparticles NP cross epithelial and endothelial body barriers. We hypothesized that gold Au NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diams.
Methods: We i. Results: We obsd. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and wt. All three sizes of AuNP were found in the placentas and amniotic fluids with 1. In the fetuses, only fractions of 0. Nanotoxicology: nanoparticles versus the placenta Nat. Pregnant mice treated nm silica nanoparticles or nm titanium dioxide nanoparticles suffer damage to the placenta and fetus, whereas larger nanoparticles do not have an adverse impact.
Nanoparticle therapeutics: an emerging treatment modality for cancer Nat. Drug Discovery , 7 , — DOI: Several nanoscaled systems for cancer therapy are approved or in clin. Here, Davis and colleagues discuss the key properties of nanotherapeutics for cancer, summarize clin. Nanoparticles - particles in the size range nm - are emerging as a class of therapeutics for cancer. Early clin. Here, we highlight the features of nanoparticle therapeutics that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities.
While large nos. Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes Environ. Objective: The unique phys. Methods: In these studies we evaluated aortic mitochondrial alterations by oxidative stress assays, including quant. Results: A single intrapharyngeal instillation of SWCNTs induced activation of heme oxygenase-1 HO-1 , a marker of oxidative insults, in lung, aorta, and heart tissue in HO-1 reporter transgenic mice.
MtDNA damage was accompanied by changes in aortic mitochondrial glutathione and protein carbonyl levels. Plaque areas in the aortas, measured by the en face method, and in the brachiocephalic arteries, measured histopathol. This response was accompanied by increased mtDNA damage but not inflammation. Conclusions: Taken together, the findings are of sufficient significance to warrant further studies to evaluate the systemic effects of SWCNT under workplace or environmental exposure paradigms.
Cardiovascular effects of pulmonary exposure to titanium dioxide nanoparticles in ApoE knockout mice J. American Scientific Publishers. Existing studies on the inhalation toxicol. The present study examd. The nano-TiO2 particles used were anatase type and the diam. We measured various indicators of inflammation, endothelial dysfunction and lipid metab. The results also showed ratio of plaque area to luminal area and the ratio of the lipid-rich core area to plaque area in the median and high nano-TiO2 dose group significantly increased resp. Our study showed that tracheal instillation of nano-TiO2 particles induced considerable systemic inflammation, endothelial dysfunction and lipid metab.
Validation assessment about the determination of selected elements in groundwater by high-resolution inductively coupled plasma mass spectrometry HR-ICPMS Int. A validation assessment of the detn. The groundwater samples, which are used for the measurements of this validation assessment, have the following concn. Besides the methodol. The validated method is routinely applied in monitoring programs.
This work can serve as a guideline for a complete validation assessment in environmental matrixes. Lankveld, Danieelle P. Aims: To develop and det. The gold content in blood and various organs was measured quant. While for the CTAB-capped gold nanorods the tissue distribution was limited to liver, spleen and lung, the PEGylated gold nanorods also distributed to kidney, heart, thymus, brain and testes. PEGylation of the gold nanorods resulted in the spleen being the organ with the highest exposure, whereas for the non-PEGylated CTAB-capped gold nanorods the liver was the organ with the highest exposure, per g of organ.
Conclusion: The PEGylation of gold nanorods resulted in a prolongation of the blood clearance and the highest organ exposure in the spleen. In view of the time frame up to 48 h of the obsd. Detecting outliers when fitting data with nonlinear regression - a new method based on robust nonlinear regression and the false discovery rate BMC Bioinf.
This assumption leads to the familiar goal of regression: to minimize the sum of the squares of the vertical or Y-value distances between the points and the curve. Outliers can dominate the sum-of-the-squares calculation, and lead to misleading results.
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However, we know of no practical method for routinely identifying outliers when fitting curves with nonlinear regression.
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