Through the magnifying glass: The effects of size and shape on the uptake, biodistribution and (eco)toxicity of nanoparticles

Although nanoparticles are extensively used in various applications like consumer products and have most probably entered the environment, little is known about the effects of these particles on living organisms. In this thesis, we aim to understand how the size and shape of nanoparticles influence their toxicity. Not only do we compare the toxic effect of these material characteristics over a series of metallic nanoparticles, therewith eliminating the effect of the core-material, but do we also investigate on an individual level where the particles migrate to inside the organism. This thesis aims to obtain a better understanding of the uptake, biodistribution and subsequent toxicity of nanoparticles, moving forward from the “organism as a black box” principle to a more detailed understanding of the harm caused by nanoparticles.Environmental Biolog

Molecular complexes of 4, 4'-dinitrobiphenyl

This study attempted to correlate the chemical and physical properties of the para disubstituted and para monosubstituted biphenyl complexes of 4,4'-DNBP with their structural and electronic properties, using a variety of physical and spectroscopic techniques, and X-ray diffraction methods. These complexes drew considerable attention in the past due to their capacity to demonstrate intense colours from yellow to dark red, which are dissimilar to the colour combination of their parent compounds. This prompted a series of investigations in the past through which the full structure of only Complex of 4,4'-Dinitrobiphenyl with 4- Hydroxybiphenyl (C-4OHBP) by single crystal diffraction was determined and the infrared and Raman spectra of C-4OHBP, Complex of 4,4'-Dinitrobiphenyl with Biphenyl (C-BP) and Complex of 4,4'-Dinitrobiphenyl with 4-Bromobiphenyl (C-BrBP) were obtained. In this study, other para-disubstituted biphenyl complexes with 4,4'-DNBP were investigated to add to the existing knowledge base and to study the effects of varying the substitution on the aromatic rings of the donor. Because the complete solid state structures of the complexes in this study (except C-4OHBP) and the donor compound BZ are not known, their single crystal determination was attempted. Unfortunately, no suitable diffraction quality crystals could be crystallised. Although the X-ray crystal structure of 4,4'-DNBP was determined by photographic methods by Van Niekerk and Boonstra, the R-factor of this solution was relatively high at 15%, which is outside the current internationally accepted standard. Because the current technology using automated diffractometers is superior to photographic techniques used by Van Niekerk and Boonstra, it was decided to repeat the crystallographic analysis for 4,4’-DNBP. However, despite repeated efforts with a large variety of solvents used during the crystallisation process in this study, the crystals formed were of a relatively poor quality, resulting in a solution with a final R-factor of also only 15%. Therefore, the only crystallographic data available for correlation with the physical properties of the complexes have been that of the uncomplexed compounds (except BZ) and C-4OHBP from the previous studies. Based on these results, the comparison of the dihedral angles between the two aromatic rings of the parent compounds with their infrared and Raman spectra yielded that, unlike the conventional compounds the centrosymmetricity of the biphenyl derivatives cannot be uniquely determined by their infrared and Raman spectra. Using thermogravimetric measurements, melting points and phase transitions of each pure component and as well as the complexes were obtained. Packing energy in the complex seems to be relatively more favourable than in the parent components alone. Otherwise, two phase transitions could be expected, one resulting from 4,4'-DNBP and one resulting from the other component in the complex. Complex of 4,4'-Dinitrobiphenyl with 4,4'-Dihydroxybiphenyl (C-44DiOHBP) and Complex of 4,4'-Dinitrobiphenyl with Benzidine (C-BZ) showed some unexpected high melting points in their thermogravimetric studies. These elevated melting points are interpreted as resulting from hydrogen bonding, and infrared studies of these complexes confirmed this interpretation. Conductivity measurements in the solid state revealed that only tmethylbz exhibits a measure of charge transfer. The absence of current in both its complexes (1:1 and 1:4 ratio) with 4,4'-DNBP was attributed to the close-packing and twisting of the components in the complex which prevented the electron flow through the complexes. Because ultraviolet-visible, infrared and Raman spectra showed only small shifts in the pure compounds after complexation in solution, and their conductivity measurements revealed no current flow, the interactions in those complexes are ascribed mainly to Van der Waals forces. The previously assigned molecular ratios are incorrect. This study has reassigned these molecular ratios using nuclear magnetic resonance techniques. Nuclear magnetic resonance spectroscopy detected only very small chemical shifts in the pure compounds after they formed complexes in solution. As these solutions did not maintain the colour of complexation, this could be seen as supportive proof that all the interactions involved in the formation of these complexes are very weak. The same conclusion as the previous studies has been reached, notably that the molecular ratios, in which the components of these complexes unite, are caused almost exclusively by packing factors and are stabilised by weak interactions.Dissertation (MSc (Chemistry))--University of Pretoria, 2007.Chemistryunrestricte

Exploring uptake and biodistribution of polystyrene (nano)particles in zebrafish embryos at different developmental stages

Conservation Biolog

Implementing the current knowledge of uptake and effects of nanoparticles in an adverse outcome pathway (AOP) framework

Unlike most other environmental pollution issues, safety assessments of nanoparticles (NPs) were meant to be the prime example on how to foresee and tackle predicted environmental concerns. For once, research efforts were ahead of mass production and potential release into environments. NPs' safety research focuses on the central question of whether the unique properties of NPs cause fundamentally different effects as compared to their larger counterparts. This chapter gives an overview of the present understanding of NP toxicity in aquatic organism. Briefly, state-of-the-art techniques to detect NPs in tissues are summarized and the present understanding of cellular and organismal NP uptake routes given. The location of NPs in tissues bears several challenges but is the first step in identifying target organs or cells and, thus, is important in the search for mechanisms of action. The evaluation of our current knowledge of cellular and organismal responses when exposed to NPs, ultimately, allows for the identification of key knowledge gaps and foresees research directions and the need to develop Adverse Outcome Pathways for NPs.Conservation Biolog

Global and national influenza-associated hospitalisation rates:Estimates for 40 countries and administrative regions

BACKGROUND: WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness (hospitalisations) every year. We aimed to improve the understanding of influenza-associated hospitalisation estimates at a national and global level. METHODS: We performed a systematic literature review of English- and Chinese-language studies published between 1995 and 2020 estimating influenza-associated hospitalisation. We included a total of 127 studies (seven in Chinese) in the meta-analysis and analyzed their data using a logit-logistic regression model to understand the influence of five study factors and produce national and global estimates by age groups. The five study factors assessed were: 1) the method used to calculate the influenza-associated hospitalisation estimates (rate- or time series regression-based), 2) the outcome measure (divided into three envelopes: narrow, medium, or wide), 3) whether every case was laboratory-confirmed or not, 4) whether the estimates were national or sub-national, 5) whether the rates were based on a single year or multiple years. RESULTS: The overall pooled influenza-associated hospitalisation rate was 40.1 (95% confidence interval (CI) = 23.3-69.1) per 100 000 persons, with rates varying substantially by age: 137.8 (95% CI = 70.6-268.7) in children aged 0-4 years and 71.6 (95% CI = 39.9-127.7) in the elderly aged >65 years. The overall pooled hospitalisation rates varied by calculation method; for all ages, the rates were significantly higher when they were based on rate-based methods or calculated on a single season and significantly lower when cases were laboratory-confirmed. The national hospitalisation rates (all ages) varied considerably, ranging from 11.7 (95% CI = 3.8-36.3) per 100 000 in New Zealand to 122.1 (95% CI = 41.5-358.4) per 100 000 in India (all age estimates). CONCLUSIONS: Using the pooled global influenza-associated hospitalisation rate, we estimate that seasonal influenza epidemics result in 3.2 million cases of severe illness (hospitalisations) per annum. More extensive analyses are required to assess the influence of other factors on the estimates (e.g. vaccination and dominant virus (sub)types) and efforts to harmonize the methods should be encouraged. Our study highlights the high rates of influenza-associated hospitalisations in children aged 0-4 years and the elderly aged 65+ years

Exploring uptake and biodistribution of polystyrene (nano)particles in zebrafish embryos at different developmental stages.

In ecotoxicology, it is continuously questioned whether (nano)particle exposure results in particle uptake and subsequent biodistribution or if particles adsorb to the epithelial layer only. To contribute to answering this question, we investigated different uptake routes in zebrafish embryos and how they affect particle uptake into organs and within whole organisms. This is addressed by exposing three different life stages of the zebrafish embryo in order to cover the following exposure routes: via chorion and dermal exposure; dermal exposure; oral and dermal exposure. How different nanoparticle sizes affect uptake routes was assessed by using polystyrene particles of 25, 50, 250 and 700nm. In our experimental study, we showed that particle uptake in biota is restricted to oral exposure, whereas the dermal route resulted in adsorption to the epidermis and gills only. Ingestion followed by biodistribution was observed for the tested particles of 25 and 50nm. The particles spread through the body and eventually accumulated in specific organs and tissues such as the eyes. Particles larger than 50nm were predominantly adsorbed onto the intestinal tract and outer epidermis of zebrafish embryos. Embryos exposed to particles via both epidermis and intestine showed highest uptake and eventually accumulated particles in the eye, whereas uptake of particles via the chorion and epidermis resulted in marginal uptake. Organ uptake and internal distribution should be monitored more closely to provide more in depth information of the toxicity of particles

Hospital Utilization Rates for Influenza and RSV:A Novel Approach and Critical Assessment

Abstract Background Influenza and respiratory syncytial virus (RSV) contribute significantly to the burden of acute lower respiratory infection (ALRI) inpatient care, but heterogeneous coding practices and availability of inpatient data make it difficult to estimate global hospital utilization for either disease based on coded diagnoses alone. Methods This study estimates rates of influenza and RSV hospitalization by calculating the proportion of ALRI due to influenza and RSV and applying this proportion to inpatient admissions with ALRI coded as primary diagnosis. Proportions of ALRI attributed to influenza and RSV were extracted from a meta-analysis of 360 total sources describing inpatient hospital admissions which were input to a Bayesian mixed effects model over age with random effects over location. Results of this model were applied to inpatient admission datasets for 44 countries to produce rates of hospital utilization for influenza and RSV respectively, and rates were compared to raw coded admissions for each disease. Results For most age groups, these methods estimated a higher national admission rate than the rate of directly coded influenza or RSV admissions in the same inpatient sources. In many inpatient sources, International Classification of Disease (ICD) coding detail was insufficient to estimate RSV burden directly. The influenza inpatient burden estimates in older adults appear to be substantially underestimated using this method on primary diagnoses alone. Application of the mixed effects model reduced heterogeneity between countries in influenza and RSV which was biased by coding practices and between-country variation. Conclusions This new method presents the opportunity of estimating hospital utilization rates for influenza and RSV using a wide range of clinical databases. Estimates generally seem promising for influenza and RSV associated hospitalization, but influenza estimates from primary diagnosis seem highly underestimated among older adults. Considerable heterogeneity remains between countries in ALRI coding (i.e., primary vs non-primary cause), and in the age profile of proportion positive for influenza and RSV across studies. While this analysis is interesting because of its wide data utilization and applicability in locations without laboratory-confirmed admission data, understanding the sources of variability and data quality will be essential in future applications of these methods

The epidemiology of dengue outbreaks in 2016 and 2017 in Ouagadougou, Burkina Faso.

BACKGROUND: Dengue is prevalent in as many as 128 countries with more than 100 million clinical episodes reported annually and four billion people estimated to be at risk. While dengue fever is systematically diagnosed in large parts of Asia and South America, the disease burden in Africa is less well investigated. This report describes two consecutive dengue outbreaks in Ouagadougou, Burkina Faso in 2016 and 2017. METHODS: Blood samples of febrile patients received at Schiphra laboratory in Ouagadougou, Burkina Faso, were screened for dengue infection using SD Bioline Dengue Duo rapid diagnostic test kits (Standard Diagnostics, Suwon, Republic of Korea). RESULTS: A total of 1,397 and 1,882 cases were reported by a single laboratory in 2016 and 2017, respectively. Most cases were at least 15 years of age and the results corroborated reports from WHO indicating the circulation of three dengue virus serotypes in Burkina Faso. CONCLUSION: This study complements data from other, simultaneously conducted surveillance efforts, and indicates that the dengue disease burden might be underestimated in sub-Saharan African nations. Dengue surveillance should be enhanced in African settings to determine the burden more accurately, and accelerated efforts towards a dengue vaccine should be put in place