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  • 1.
    Andersson, Patrik
    et al.
    AstraZeneca R&D, Mölndal, Sweden.
    Kenne, Kerstin
    AstraZeneca R&D, Södertälje, Sweden.
    Glinghammar, Björn
    AstraZeneca R&D, Södertälje, Sweden.
    Pointon, Amy V.
    Global Safety Assessment AstraZeneca, Macclesfield, United Kingdom.
    Åkerblad, Peter
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Lutz, Mareike
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Hovdal, Daniel
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Maxvall, Ingela
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Lindstedt, Eva-Lotte
    CVGI iMed AstraZeneca, Mölndal, Sweden.
    Toxicity with LXR agonists – Problem solving activities for mechanistic understanding2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Suppl. (S), p. S39-S39Article in journal (Refereed)
    Abstract [en]

    Several lines of evidence points toward the potential positive effects of LXR (Liver X Receptor) modulators for effective and safe therapy of cardiovascular diseases (CVDs). LXR is a dimeric nuclear hormone receptor that exists as a combination of RXR and one of two subtypes LXR alpha or beta, which act as cholesterol sensors. LXR alpha is highly expressed in the liver, intestine and adipose tissue while LXR beta is ubiquitously expressed. Activation of LXR up-regulates several genes involved in reverse cholesterol transport (RCT), including ABC transporters. This results in increased efflux of cholesterol from macrophages in atherosclerotic vascular lesions to the circulation and further on to other tissues to ultimately be excreted into the faeces. These effects together with systemic and local anti-inflammatory properties of LXR modulation are likely to contribute to decreased atherosclerosis. The positive effects of LXR activation on RCT and cholesterol balance must be obtained without negative lipid effects, since LXR also activates lipogenic genes. Other types of toxicity and approaches to better understand the mechanism(s) behind these will be presented. Copyright © 2012 Published by Elsevier Ireland Ltd.

  • 2.
    Desbans, Coraline
    et al.
    KaLy-Cell, Plobsheim, France.
    Hilgendorf, Constanze
    UCB Pharma S.A, Braine-l'Alleud, Belgium.
    Lutz, Mareike
    Halmstad University.
    Bachellier, P
    Centre de Chirurgie Viscérale et de Transplantation, Hôpital de Hautepierre, Strasbourg, France.
    Zacharias, T
    Service de Chirurgie Viscérale et Digestive, Centre Hospitalier Emile Muller-Moenchsberg, Mulhouse, France.
    Weber, JC
    Clinique de l'Orangerie, Strasbourg, France.
    Dolgos, Hugues
    UCB Pharma S.A, Braine-l'Alleud, Belgium.
    Richert, Lysiane
    KaLy-Cell, Plobsheim, France.
    Ungell, Anna-Lena
    UCB Pharma S.A, Braine-l'Alleud, Belgium.
    Prediction of fraction metabolized via CYP3A in humans utilizing cryopreserved human hepatocytes from a set of 12 single donors2014In: Xenobiotica, ISSN 0049-8254, E-ISSN 1366-5928, Vol. 44, no 1, p. 17-27Article in journal (Refereed)
  • 3.
    Eriksson, K.M.
    et al.
    Department of Plant and Environmental Sciences, University of Gothenburg, Sweden.
    Clarke, A.K.
    Department of Plant and Environmental Sciences, University of Gothenburg, Sweden.
    Franzén, Lars-Gunnar
    Halmstad University, School of Business and Engineering (SET), Biological and Environmental Systems (BLESS), Plant Cell Biology: Energy transduction in plant cells.
    Kuylenstierna, M.
    Department of Marine Ecology, University of Gothenburg, Sven Lovén Centre for Marine Sciences Kristineberg, Fiskebäckskil, Sweden.
    Martinez, K.
    Spanish National Research Council—IIQAB-CSIC, Department of Ecotechnology, Josep Pascual Vila, Barcelona, Spain .
    Blanck, H.
    Department of Plant and Environmental Sciences, University of Gothenburg, Sweden.
    Community-Level Analysis of psbA Gene Sequences and Irgarol Tolerance in Marine Periphyton2009In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 75, no 4, p. 897-906Article in journal (Refereed)
    Abstract [en]

    This study analyzes psbA gene sequences, predicted D1 protein sequences, species relative abundance, and pollution-induced community tolerance in marine periphyton communities exposed to the antifouling compound Irgarol 1051. The mechanism of action of Irgarol is the inhibition of photosynthetic electron transport at photosystem II by binding to the D1 protein. The metagenome of the communities was used to produce clone libraries containing fragments of the psbA gene encoding the D1 protein. Community tolerance was quantified with a short-term test for the inhibition of photosynthesis. The communities were established in a continuous flow of natural seawater through microcosms with or without added Irgarol. The selection pressure from Irgarol resulted in an altered species composition and an inducted community tolerance to Irgarol. Moreover, there was a very high diversity in the psbA gene sequences in the periphyton, and the composition of psbA and D1 fragments within the communities was dramatically altered by increased Irgarol exposure. Even though tolerance to this type of compound in land plants often depends on a single amino acid substitution (Ser(264)-> Gly) in the D1 protein, this was not the case for marine periphyton species. Instead, the tolerance mechanism likely involves increased degradation of D1. When we compared sequences from low and high Irgarol exposure, differences in nonconserved amino acids were found only in the so-called PEST region of D1, which is involved in regulating its degradation. Our results suggest that environmental contamination with Irgarol has led to selection for high-turnover D1 proteins in marine periphyton communities at the west coast of Sweden.

  • 4.
    Hellström, Sandra
    et al.
    Halmstad University, School of Social and Health Sciences (HOS).
    Nyberg, Frida
    Halmstad University, School of Social and Health Sciences (HOS).
    Tbc, ett globalt hot: Sjuksköterskans arbete för att främja följsamhet och minska resistensutveckling av mykobakterium tuberkulosis2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Tuberculosis (TB) is an airborne droplet infection caused by mycobacterium tuberculosis. TB is the disease after AIDS that is most deadly, even though curative treatment exists. The treatment is demanding for the TB-infected to undergo and consists of a combination of a number of antibiotics that must be administered for at least six months. A dissenting in anti-tuberculosis treatment might result in mycobacterium tuberculosis strains that are resistant to antibiotics. As adherence to long-term treatment is graded at a low percentage (50 %) the aim of the literature study was from a global perspective to develop a working-strategy for nurses that promote compliance in TB-treatment in order to reduce resistance development of mycobacterium tuberculosis. The study was conducted as a literature study where 12 research articles were reviewed and analyzed. The results describe specific factors that are essential to compliance. These factors comprise patient education, treatment strategies, social influences and support. As knowledge gives the patient a better understanding for the treatment it provokes compliance. The social environment of the TB-infected patient demands increased knowledge in order to reduce stigma. Several studies show that the DOTS strategy is important for increasing compliance in anti-tuberculosis treatment. The literature study results in a proposal for the nursing program to focus more on compliance in taking medication. The nursing program’s attendants need to gain knowledge about prudent antibiotic treatment that leads to a compliance concern.

  • 5.
    Johansson, Jeanette
    et al.
    Halmstad University, School of Social and Health Sciences (HOS).
    Särnbäck, Marie
    Halmstad University, School of Social and Health Sciences (HOS).
    Polyfarmaci hos äldre:  – ett världsomfattande hälsoproblem   2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The elderly population is increasing all over the world. Aging is associated with diseases resulting in increased medical consumption. Elderly over 80 years consume in average 5,8 different drugs. Nursing home residents consume ten drugs which represents an increase of 60 % within the last two decades. This development is based on the increasing progress within the field medical treatment. Polypharmacy and inappropriate prescribing in elderly over 65 years, according to Beer´s criteria (annex I), results in a growing and worldwide health problem. Polypharmacy comprises use of multiple drugs (mostly five or more per day). Polypharmacy is associated with increased age and is most common in women and low educated individuals. Multiple medications increase the risk of adverse drug reactions and drug-drug interactions especially in old and frail persons with comorbidity. The aim of the study was to elucidate the prevalence and the consequences of polypharmacy and inappropriate prescribing in elderly. The study was based on a literature study in which 17 articles were analyzed. The result shows that one third of the elderly patients consume inappropriate medications, according to Beer´s criteria, which are associated with unnecessary suffering and increased hospital admission. It´s important that health care personnel gains understanding about the pharmacological consequences of body composition changes in older adults. Nurses and physicians should also improve their cooperation with pharmacists to increase knowledge leading to better patient safety.

  • 6.
    Panosyan, Luiza
    Halmstad University, School of Business and Engineering (SET).
      Impact of vehicle exhaust emitted by the combustion of biofuels on human health2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

     

    Introduction: Significant changes in the global ecosystem, together with a potential shortfall in oil resources, have stimulated intense interest in the development of other sources of energy, and most particularly biofuels since these are basically considered to be less harmful to human health than petroleum-based fuels. However, information about the impact of biofuel-derived vehicle emissions on human health is limited and incomplete.

     

    Aim of the study: To identify those biofuels that are less detrimental to human health on the basis of published results from toxicological and chemical studies of vehicle emission products.

     

    Tasks of the study: To review systematically all conventional and alternative fuels used in internal combustion engines, to identify all known toxic emission products formed by such fuels, to review their toxic effects on human health, and to analyse the data collected in order to develop conclusions concerning the possible health benefits deriving from the use of alternative fuels.

     

    Materials and methods: In order to fulfil the requirements of a complete, comprehensive and up-to-date review of the toxic effects of automotive exhaust, an extensive search of official scientific data sources has been performed. Relevant publications were retrieved from public domain databases with a toxicological focus such as Toxcenter and CAplus, as well as from the websites of the US Environmental Protection Agency and the US Agency for Toxic Substances and Disease Registry. Keywords employed in the literature search were: petrol, gasoline, diesel exhaust, emission, biofuel, biogas, biodiesel, bioethanol, bioalcohol, toxicity, methanol and ethanol. A total of 295 references were initially selected relating to the period 1962 to 2008, and 142 of these presented titles and abstracts that met the main inclusion criteria, i.e. describing toxicological and epidemiological studies in humans. In cases where eligible studies relating to the goals and tasks of the review were limited or not available, some in vitro or in vivo toxicological studies involving animal models were included.

     

    Results: In comparison with petroleum diesel, the emissions derived from biodiesel contain less particulate matter, carbon monoxide, total hydrocarbons and other toxic compounds including vapour-phase C1-C12 hydrocarbons, aldehydes and ketones (up to C8), selected semi-volatile and particle-phase polycyclic aromatic hydrocarbons (PAHs). Whilst sulphur-containing compounds appear to be undetectable in biodiesel, nitrogen oxide and a soluble organic fraction comprising unregulated pollutants including the “aggregated toxics” (i.e., formaldehyde, acetaldehyde, acrolein, benzene, 1,3-butadiene, ethylbenzene, n-hexane, naphthalene, styrene, toluene and xylene) are present at elevated levels. Toxicological studies have shown that the mutagenicity of exhaust particles from biodiesel is normally lower than those obtained from petroleum diesel, however, rapeseed oil-derived biodiesel exhibits toxic effects that are 4-fold greater than petroleum diesel. Such enhanced toxicity is probably caused by the presence of carbonyl compounds and unburnt fuel. The toxicity of highly volatile components of biofuel exhaust has not yet been evaluated accurately. A substantial portion of these compounds was apparently lost in the process of preparing the test samples used for the assays (during the evaporation). The overall recoveries of these compounds have not been evaluated and the accuracy of the sample preparation method has not been validated. Hence, it could be that the cytotoxic effect of biodiesel exhaust is higher than that reported. Moreover, compared with fossil diesel, fuel derived from rapeseed oil emits particulate matter with increased mutagenic effects. Epidemiological investigations of the effects of biofuels on humans are very sparse but have revealed dose-dependent respiratory symptoms following exposure to rapeseed oil biodiesel, although the observed differences between this fuel and petroleum diesel are not significant. Such data, however, give rise to serious concerns about the future usage of this plant material as a replacement for established diesel fuels. Combustion of alcohol-based fuels leads to a reduced formation of photochemical smog in comparison with gasoline or diesel, however, the emission of aldehydes (officially classified as carcinogenic or potentially carcinogenic) is several times higher. The toxicity of the exhaust emissions of gasoline-fuelled engines is generally significantly greater than that of alcohol-burning engines. However, some harmful effects from ethanol blends might be expected, such as enhanced emissions of carcinogenic PAHs and increased ozone-related toxicity associated with the high level of aldehydes emitted. The use of ethanol–diesel fuel blends gives rise to increases in regulated exhaust emissions and, possibly, to greater emissions of aldehydes and unburnt hydrocarbons. The most promising fuels, in terms of reduced toxicity and genotoxicity of exhaust emissions, are methanol-containing blends. However, the emission from these fuels still contains formaldehyde, which is a carcinogen. The use of biogas can significantly reduce emissions of total PAHs and formaldehyde and, consequently, the risk of lung toxicity. On the other hand, the emissions of particulate matter by compressed natural gas, and the mutagenic potencies of the exhaust, are similar to those associated with gasoline and diesel fuels.

     

    Conclusions: The use of biofuel is currently viewed very favourably and there are suggestions that the exhaust emissions from such fuel are less likely to present risks to human health in comparison with gasoline and diesel emissions. However, the expectation of a reduction in health effects based on the chemical composition of biodiesel exhaust is far from reality. Thus, although toxicological evidence relating to the effects of biofuels on humans is sparse, it is already apparent that emissions from the combustion of biofuel and blends thereof with petroleum-based fuels are toxic. In addition to the regulated toxic compounds, such as total hydrocarbons, carbon monoxide, nitrogen oxides, particulate matter and polycyclic aromatic hydrocarbons, biofuel emissions contain significant amounts of various other harmful substances that are not regulated, e.g. carbonyls (including formaldehyde, acetaldehyde, benzene, 3-butadiene, acrolein, etc.). Whilst biofuels may be potentially less damaging to human health than petroleum fuels, considerable harmful effects must still be expected. Substitution of conventional fuel by biofuel decreases the concentration of regulated toxic pollutants in vehicle exhaust, but increases the concentration of some unregulated toxic pollutants emitted from on-road engines. Generally, the toxicity of biofuels decreases in the order biodiesel>biogas>ethanol>=methanol. In this respect, methanol produced by the oxidation of biogas appears to represent an alternative fuel that exhibits the least potential for damage to human health, however, this alcohol represents a source of formaldehyde pollution and is carcinogenic.

    .

     

  • 7.
    Urrutia-Cordero, Pablo
    et al.
    Halmstad University, School of Business, Engineering and Science. Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Agha, Ramsy
    Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Cires, Samuel
    Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Angeles Lezcano, Maria
    Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Sanchez-Contreras, Maria
    Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Waara, Karl-Otto
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS).
    Utkilen, Hans
    Norwegian Inst Publ Hlth, Dept Water Hyg, N-0403 Oslo, Norway..
    Quesada, Antonio
    Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain..
    Effects of harmful cyanobacteria on the freshwater pathogenic free-living amoeba Acanthamoeba castellanii2013In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 130, p. 9-17Article in journal (Refereed)
    Abstract [en]

    Grazing is a major regulating factor in cyanobacterial population dynamics and, subsequently, considerable effort has been spent on investigating the effects of cyanotoxins on major metazoan grazers. However, protozoan grazers such as free-living amoebae can also feed efficiently on cyanobacteria, while simultaneously posing a major threat for public health as parasites of humans and potential reservoirs of opportunistic pathogens. In this study, we conducted several experiments in which the freshwater amoeba Acanthamoeba castellanii was exposed to pure microcystin-LR (MC-LR) and six cyanobacterial strains, three MC-producing strains (MC-LR, MC-RR, MC-YR, MC-WR, [Dha7] MC-RR) and three strains containing other oligopeptides such as anabaenopeptins and cyanopeptolins. Although the exposure to high concentrations of pure MC-LR yielded no effects on amoeba, all MC-producing strains inflicted high mortality rates on amoeba populations, suggesting that toxic effects must be mediated through the ingestion of toxic cells. Interestingly, an anabaenopeptin-producing strain caused the greatest inhibition of amoeba growth, indicating that toxic bioactive compounds other than MCs are of great importance for amoebae grazers. Confocal scanning microscopy revealed different alterations in amoeba cytoskeleton integrity and as such, the observed declines in amoeba densities could have indeed been caused via a cascade of cellular events primarily triggered by oligopeptides with protein-phosphatase inhibition capabilities such as MCs or anabaenopeptins. Moreover, inducible-defense mechanisms such as the egestion of toxic, MC-producing cyanobacterial cells and the increase of resting stages (encystation) in amoebae co-cultivated with all cyanobacterial strains were observed in our experiments. Consequently, cyanobacterial strains showed different susceptibilities to amoeba grazing which were possibly influenced by the potentiality of their toxic secondary metabolites. Hence, this study shows the importance of cyanobacterial toxicity against amoeba grazing and, that cyanobacteria may contain a wide range of chemical compounds capable of negatively affect free-living, herbivorous amoebae. Moreover, this is of high importance for understanding the interactions and population dynamics of such organisms in aquatic ecosystems. (c) 2012 Elsevier B.V. All rights reserved.

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