27 results on '"Vasskog T"'
Search Results
2. Pharmaceutical Residues in Northern European Environments: Consequences and Perspectives
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Kallenborn, R., Fick, J., Lindberg, R., Moe, M., Nielsen, K. M., Tysklind, M., Vasskog, T., and Kümmerer, Klaus, editor
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- 2008
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Catalog
3. Lipid content and fatty acid composition of Porosira glacialis and Attheya longicornis in response to carbon dioxide (CO2) aeration
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Artamonova, E. Y., primary, Vasskog, T., additional, and Eilertsen, H. C., additional
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- 2017
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4. Lipid content and fatty acid composition of Porosira glacialis and Attheya longicornis in response to carbon dioxide (CO2) aeration.
- Author
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Artamonova, E. Y., Vasskog, T., and Eilertsen, H. C.
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- *
DIATOMS , *BODY composition , *PHYSIOLOGICAL effects of carbon dioxide , *PHYSIOLOGICAL effects of greenhouse gases , *INDUSTRY & the environment , *PHYSIOLOGY - Abstract
In the current study two novel psychrophilic diatoms Porosira glacialis and Attheya longicornis were tested for suitability to CO2 mitigation coupled with production of the physiologically requisite omega– 3 fatty acids. This study is in line with the worldwide conducted research aimed at applying biorefinery concept to heavy polluting industries. Since the production of algal high value compounds, i.e. essential fatty acids, relies on utilization of residual CO2 emissions coming from industry, the costs of such production maybe substantially reduced. Besides, the ecological benefits of the biorefinery concept being implemented are obvious, since CO2 is one of the major greenhouse gases. The current research has shown that one of the tested microalgal species, the diatom P. glacialis showed good tolerance to high (20–25%) levels of CO2 and maintained growth rates comparable to controls. The total lipid content in the CO2 aerated culture increased from 8.91 to 10.57% in cell dry mass. Additionally, the content of docosahexaenoic acid (DHA) increased from 3.90 to 5.75%, while the concentration of eicosapentaenoic acid (EPA) decreased from 26.59 to 23.66%. In contrast, A. longicornis did not demonstrate any significant increase in total lipid content. Besides, its growth was hampered by high levels of CO2 aeration. [ABSTRACT FROM AUTHOR] more...
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- 2017
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5. Pharmaceutical Residues in Northern European Environments: Consequences and Perspectives
- Author
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Kallenborn, R., primary, Fick, J., additional, Lindberg, R., additional, Moe, M., additional, Nielsen, K. M., additional, Tysklind, M., additional, and Vasskog, T., additional
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6. Pharmaceutical residues in Northern European Environments : Consequences and Perspectives
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Kallenborn, R, Fick, Jerker, Lindberg, Richard, Moe, M, Nielsen, K M, Tysklind, Mats, Vasskog, T, Kallenborn, R, Fick, Jerker, Lindberg, Richard, Moe, M, Nielsen, K M, Tysklind, Mats, and Vasskog, T
- Abstract
About this book The study of pharmaceuticals in the environment as an area of research has only just taken off in recent years. Since the first edition was printed, many research articles on this subject have been published. It is exceedingly difficult for the individual, in particular those not acquainted with the field to establish trends and developments. Even specialists will appreciate this book, as it provides the reader with a well-founded up dated and enlarged overview that addresses the latest findings on the new topics in research.Following the resounding success of the first two editions, this new edition has been brought up to date and greatly extended. It includes the status of research, paying particular attention to sources and contamination of the environment, substance flows, effects, risk assessment and risk management. In line with the newest developments worldwide there are again contributions from well known and new international authors. This volume also caters for the new requirements confronting European and American researchers since publication of the second edition.Written for:Libraries, institutes, researchers, scientists in the fields of environmental sciences including environmental medicine, microbiology, analytical chemistry more...
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- 2008
7. Validation of two LCHRMS methods for large-scale untargeted metabolomics of serum samples: Strategy to establish method fitness-for-purpose.
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Grijseels S, Vasskog T, Heinsvig PJ, Myhre TN, Hansen T, and Mardal M
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- Humans, Reproducibility of Results, Chromatography, Liquid methods, Mass Spectrometry methods, Metabolome, Metabolomics methods
- Abstract
Untargeted metabolomics by LCHRMS is a powerful tool to enhance our knowledge of pathophysiological processes. Whereas validation of a bioanalytical method is customary in most analytical chemistry fields, it is rarely performed for untargeted metabolomics. This study aimed to establish and validate an analytical platform for a long-term, clinical metabolomics study. Sample preparation was performed with an automated liquid handler and four analytical methods were developed and evaluated. The validation study spanned three batches with twelve runs using individual serum samples and various quality control samples. Data was acquired with untargeted acquisition and only metabolites identified at level 1 were evaluated. Validation parameters were set to evaluate key performance metrics relevant for the intended application: reproducibility, repeatability, stability, and identification selectivity, emphasizing dataset intrinsic variance. Concordance of semi-quantitative results between methods was evaluated to identify potential bias. Spearman rank correlation coefficients (r
s ) were calculated from individual serum samples. Of the four methods tested, two were selected for validation. A total of 47 and 55 metabolites (RPLC-ESI+ - and HILIC-ESI- -HRMS, respectively) met specified validation criteria. Quality assurance involved system suitability testing, sample release, run release, and batch release. The median repeatability and within-run reproducibility as coefficient of variation% for metabolites that passed validation on RPLC-ESI+ - and HILIC-ESI- -HRMS were 4.5 and 4.6, and 1.5 and 3.8, respectively. Metabolites that passed validation on RPLC-ESI+ -HRMS had a median D-ratio of 1.91, and 89 % showed good signal intensity after ten-fold dilution. The corresponding numbers for metabolites with the HILIC-ESI- -HRMS method was 1.45 and 45 %, respectively. The rs median ({range}) for metabolites that passed validation on RPLC-ESI+ - was 0.93 (N = 9 {0.69-0.98}) and on HILIC-ESI- -HRMS was 0.93 (N = 22 {0.55-1.00}). The validated methods proved fit-for-purpose and the laboratory thus demonstrated its capability to produce reliable results for a large-scale, untargeted metabolomics study. This validation not only bolsters the reliability of the assays but also significantly enhances the impact and credibility of the hypotheses generated from the studies. Therefore, this validation study serves as a benchmark in the documentation of untargeted metabolomics, potentially guiding future endeavors in the field., Competing Interests: Declaration of competing interest The authors declare that they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.) more...- Published
- 2024
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8. Lipidome Plasticity Enables Unusual Photosynthetic Flexibility in Arctic vs. Temperate Diatoms.
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Svenning JB, Vasskog T, Campbell K, Bæverud AH, Myhre TN, Dalheim L, Forgereau ZL, Osanen JE, Hansen EH, and Bernstein HC
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- Lipidomics, Photosynthesis physiology, Light, Lipids, Diatoms chemistry
- Abstract
The diatom lipidome actively regulates photosynthesis and displays a high degree of plasticity in response to a light environment, either directly as structural modifications of thylakoid membranes and protein-pigment complexes, or indirectly via photoprotection mechanisms that dissipate excess light energy. This acclimation is crucial to maintaining primary production in marine systems, particularly in polar environments, due to the large temporal variations in both the intensity and wavelength distributions of downwelling solar irradiance. This study investigated the hypothesis that Arctic marine diatoms uniquely modify their lipidome, including their concentration and type of pigments, in response to wavelength-specific light quality in their environment. We postulate that Arctic-adapted diatoms can adapt to regulate their lipidome to maintain growth in response to the extreme variability in photosynthetically active radiation. This was tested by comparing the untargeted lipidomic profiles, pigmentation, specific growth rates and carbon assimilation of the Arctic diatom Porosira glacialis vs. the temperate species Coscinodiscus radiatus during exponential growth under red, blue and white light. Here, we found that the chromatic wavelength influenced lipidome remodeling and growth in each strain, with P. glacialis showing effective utilization of red light coupled with increased inclusion of primary light-harvesting pigments and polar lipid classes. These results indicate a unique photoadaptation strategy that enables Arctic diatoms like P. glacialis to capitalize on a wide chromatic growth range and demonstrates the importance of active lipid regulation in the Arctic light environment. more...
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- 2024
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9. Bacterial extracellular vesicles: towards realistic models for bacterial membranes in molecular interaction studies by surface plasmon resonance.
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Bril'kov MS, Stenbakk V, Jakubec M, Vasskog T, Kristoffersen T, Cavanagh JP, Ericson JU, Isaksson J, and Flaten GE
- Abstract
One way to mitigate the ongoing antimicrobial resistance crisis is to discover and develop new classes of antibiotics. As all antibiotics at some point need to either cross or just interact with the bacterial membrane, there is a need for representative models of bacterial membranes and efficient methods to characterize the interactions with novel molecules -both to generate new knowledge and to screen compound libraries. Since the bacterial cell envelope is a complex assembly of lipids, lipopolysaccharides, membrane proteins and other components, constructing relevant synthetic liposome-based models of the membrane is both difficult and expensive. We here propose to let the bacteria do the hard work for us. Bacterial extracellular vesicles (bEVs) are naturally secreted by Gram-negative and Gram-positive bacteria, playing a role in communication between bacteria, as virulence factors, molecular transport or being a part of the antimicrobial resistance mechanism. bEVs consist of the bacterial outer membrane and thus inherit many components and properties of the native outer cell envelope. In this work, we have isolated and characterized bEVs from one Escherichia coli mutant and three clinical strains of the ESKAPE pathogens Klebsiella pneumoniae , Acinetobacter baumannii , and Pseudomonas aeruginosa . The bEVs were shown to be representative models for the bacterial membrane in terms of lipid composition with speciesstrain specific variations. The bEVs were further used to probe the interactions between bEV and antimicrobial peptides (AMPs) as model compounds by Surface Plasmon Resonance (SPR) and provide proof-of-principle that bEVs can be used as an easily accessible and highly realistic model for the bacterial surface in interaction studies. This further enables direct monitoring of the effect induced by antibiotics, or the response to host-pathogen interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bril’kov, Stenbakk, Jakubec, Vasskog, Kristoffersen, Cavanagh, Ericson, Isaksson and Flaten.) more...
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- 2023
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10. Synthesis and Antimicrobial Activity of Short Analogues of the Marine Antimicrobial Peptide Turgencin A: Effects of SAR Optimizations, Cys-Cys Cyclization and Lipopeptide Modifications.
- Author
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Dey H, Simonovic D, Norberg-Schulz Hagen I, Vasskog T, Fredheim EGA, Blencke HM, Anderssen T, Strøm MB, and Haug T
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- Humans, Cyclization, Antimicrobial Peptides, Peptides, Cyclic pharmacology, Peptides, Cyclic chemistry, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Escherichia coli, Hemolysis, Lipopeptides pharmacology, Lipopeptides chemistry, Anti-Infective Agents pharmacology, Anti-Infective Agents chemistry
- Abstract
We have synthesised short analogues of the marine antimicrobial peptide Turgencin A from the colonial Arctic ascidian Synoicum turgens. In this study, we focused on a central, cationic 12-residue Cys-Cys loop region within the sequence. Modified (tryptophan- and arginine-enriched) linear peptides were compared with Cys-Cys cyclic derivatives, and both linear and Cys-cyclic peptides were N-terminally acylated with octanoic acid (C
8 ), decanoic acid (C10 ) or dodecanoic acid (C12 ). The highest antimicrobial potency was achieved by introducing dodecanoic acid to a cyclic Turgencin A analogue with low intrinsic hydrophobicity, and by introducing octanoic acid to a cyclic analogue displaying a higher intrinsic hydrophobicity. Among all tested synthetic Turgencin A lipopeptide analogues, the most promising candidates regarding both antimicrobial and haemolytic activity were C12 -cTurg-1 and C8 -cTurg-2 . These optimized cyclic lipopeptides displayed minimum inhibitory concentrations of 4 µg/mL against Staphylococcus aureus , Escherichia coli and the fungus Rhodothorula sp. Mode of action studies on bacteria showed a rapid membrane disruption and bactericidal effect of the cyclic lipopeptides. Haemolytic activity against human erythrocytes was low, indicating favorable selective targeting of bacterial cells. more...- Published
- 2022
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11. Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer.
- Author
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Fleten KG, Eksteen JJ, Mauseth B, Camilio KA, Vasskog T, Sveinbjørnsson B, Rekdal Ø, Mælandsmo GM, and Flatmark K
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- Animals, Cell Line, Tumor, Cell Survival drug effects, Colorectal Neoplasms drug therapy, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Disease Models, Animal, Mice, Proteolysis, Treatment Outcome, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Immunity drug effects, Immunologic Factors pharmacology, Peptides pharmacology
- Abstract
Oncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection in subcutaneous tumors established from murine CRC cell lines CT26 and MC38, and complete regression was obtained in the majority of animals. When cured animals were rechallenged by splenic injection of tumor cells, 1/23 animals developed liver metastases, compared to 19/22 naïve animals. Treatment with both peptides was well tolerated, but monitoring post-injection hemodynamic parameters in rats, less extensive changes were observed with DTT-205 than DTT-304, favoring DTT-205 for future drug development. DTT-205 was subsequently shown to have strong in vitro activity in a panel of 33 cancer cell lines. In conclusion, both peptides exerted a strong inhibitory effect in two immunocompetent CRC models and induced a systemic effect preventing development of liver metastases upon splenic rechallenge. If a similar effect could be obtained in humans, these drugs would be of particular interest for combinatory treatment with immune checkpoint inhibitors in metastatic CRC. more...
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- 2021
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12. Lipid yield from the diatom Porosira glacialis is determined by solvent choice and number of extractions, independent of cell disruption.
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Svenning JB, Dalheim L, Vasskog T, Matricon L, Vang B, and Olsen RL
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- Biomass, Cell Wall, Chemical Fractionation, Chromatography, Gas, Chromatography, High Pressure Liquid, Fatty Acids chemistry, Fatty Acids isolation & purification, Industrial Microbiology, Lipids analysis, Lipids classification, Chlorella vulgaris chemistry, Diatoms chemistry, Lipids chemistry, Plant Extracts chemistry, Plant Extracts isolation & purification, Solvents chemistry
- Abstract
Cell wall disruption is necessary to maximize lipid extraction yields in conventional species of mass-cultivated microalgae. This study investigated the effect of sonication, solvent choice and number of extractions on the lipid yield, lipid class composition and fatty acid composition of the diatom Porosira glacialis. For comparison, the diatom Odontella aurita and green alga Chlorella vulgaris were included in the study. Sonication effectively disrupted P. glacialis cells, but did not increase the total lipid yield compared to physical stirring (mixing). In all three microalgae, the content of membrane-associated glyco- and phosopholipids in the extracted lipids was strongly dependent on the solvent polarity. A second extraction resulted in higher yields from the microalgae only when polar solvents were used. In conclusion, choice of solvent and number of extractions were the main factors that determined lipid yield and lipid class composition in P. glacialis. more...
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- 2020
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13. Selective Intracellular Delivery of Thiolated Cargo to Tumor and Neovasculature Cells Using Histidine-Rich Peptides as Vectors.
- Author
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Eksteen JJ, Ausbacher D, Vasskog T, Rekdal Ø, and Svendsen JSM
- Abstract
Short histidine-rich peptides could serve as novel activatable vectors for delivering cytotoxic payloads to tumor and neovasculature cells. This explorative study reports preliminary results showing that zinc ions, which are found in elevated levels at neovasculature sites, can trigger the intracellular delivery of a short antimicrobial peptide when conjugated to a histidine-rich peptide through a disulfide bond. The importance of exofacial thiols in the mode of action of these disulfide-linked conjugates is also shown., Competing Interests: The authors declare the following competing financial interest(s): ØR is the CSO of the Lytix Biopharma AS. ØR and JSMS are minor shareholders in Lytix Biopharma AS., (Copyright © 2020 American Chemical Society.) more...
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- 2020
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14. Evaluation by metabolic profiling and in vitro autoradiography of two promising GnRH-receptor ligands for brain SPECT imaging.
- Author
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Fjellaksel R, Moldes-Anaya A, Vasskog T, Oteiza A, Martin-Armas M, Hjelstuen OK, Hansen JH, Riss PJ, and Sundset R
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- Animals, Rats, Humans, Ligands, Radiopharmaceuticals pharmacokinetics, Radiopharmaceuticals chemistry, Radiopharmaceuticals chemical synthesis, Microsomes, Liver metabolism, Male, Tomography, Emission-Computed, Single-Photon methods, Brain metabolism, Brain diagnostic imaging, Autoradiography methods, Receptors, LHRH metabolism
- Abstract
The increased expression of gonadotropin releasing hormone receptor (GnRH-R) in brain has been strongly linked to Alzheimer disease. Therefore, the development of radiolabeled imaging agents for GnRH-R is relevant for early diagnosis of Alzheimer disease. We have recently disclosed the discovery of two promising compounds displaying nanomolar-range affinity for the GnRH-R. In the present study, a preclinical evaluation of the compound properties was performed to evaluate their potential as single photon emission computed tomography (SPECT) radiotracers for imaging the GnRH-receptor. The compounds were assessed in vitro by performing serum stability analysis by human and rat serum, metabolic profiling by human liver microsomes, and exploratory rat brain autoradiography. The investigated compounds displayed satisfactory stability against human, rat serum, and liver microsomal metabolism, which favors their potential as SPECT-imaging agents. Additionally, we identified and quantified the formation rate of the metabolites by fragmentation of up to five mass spectrometric stages. The GnRH-R rat brain specificity of these compounds was tested in competition with a known ligand for the receptor and the in vitro autoradiography confirmed that compounds 3 and 4 binds to rat GnRH-R in different rat brain regions., (© 2019 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.) more...
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- 2020
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15. The three-dimensional structure of an H-superfamily conotoxin reveals a granulin fold arising from a common ICK cysteine framework.
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Nielsen LD, Foged MM, Albert A, Bertelsen AB, Søltoft CL, Robinson SD, Petersen SV, Purcell AW, Olivera BM, Norton RS, Vasskog T, Safavi-Hemami H, Teilum K, and Ellgaard L
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- Amino Acid Sequence, Animals, Conotoxins genetics, Conotoxins metabolism, Disulfides chemistry, Granulins metabolism, Magnetic Resonance Spectroscopy, Mollusk Venoms metabolism, Protein Conformation, beta-Strand, Protein Folding, Protein Stability, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Recombinant Proteins genetics, Conotoxins chemistry, Conus Snail metabolism, Cysteine chemistry, Granulins chemistry
- Abstract
Venomous marine cone snails produce peptide toxins (conotoxins) that bind ion channels and receptors with high specificity and therefore are important pharmacological tools. Conotoxins contain conserved cysteine residues that form disulfide bonds that stabilize their structures. To gain structural insight into the large, yet poorly characterized conotoxin H-superfamily, we used NMR and CD spectroscopy along with MS-based analyses to investigate H-Vc7.2 from Conus victoriae , a peptide with a VI/VII cysteine framework. This framework has Cys
I -CysIV /CysII -CysV /CysIII -CysVI connectivities, which have invariably been associated with the inhibitor cystine knot (ICK) fold. However, the solution structure of recombinantly expressed and purified H-Vc7.2 revealed that although it displays the expected cysteine connectivities, H-Vc7.2 adopts a different fold consisting of two stacked β-hairpins with opposing β-strands connected by two parallel disulfide bonds, a structure homologous to the N-terminal region of the human granulin protein. Using structural comparisons, we subsequently identified several toxins and nontoxin proteins with this "mini-granulin" fold. These findings raise fundamental questions concerning sequence-structure relationships within peptides and proteins and the key determinants that specify a given fold., (© 2019 Nielsen et al.) more...- Published
- 2019
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16. Preparation and Assessment of Self-Immolative Linkers for Therapeutic Bioconjugates with Amino- and Hydroxyl-Containing Cargoes.
- Author
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Sengee M, Eksteen JJ, Nergård SL, Vasskog T, and Sydnes LK
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- Amines chemistry, Peptides chemistry, Pharmaceutical Preparations chemistry, Sulfhydryl Compounds chemistry
- Abstract
A series of self-immolative linkers containing a thiol-reactive group at one end and a hydroxyl- or amine-reactive group at the other were prepared. The utility of these reagents for preparations of bioconjugates was explored by reacting the linkers with appropriately functionalized model drugs and peptides. Degradation studies of a series of conjugates with different linkers reveal that the structure of the linkers has a significant impact on their stability. more...
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- 2019
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17. General Approach To Determine Disulfide Connectivity in Cysteine-Rich Peptides by Sequential Alkylation on Solid Phase and Mass Spectrometry.
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Albert A, Eksteen JJ, Isaksson J, Sengee M, Hansen T, and Vasskog T
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- Alkylation, Amino Acid Sequence, Oxidation-Reduction, Disulfides chemistry, Peptides chemistry, Sequence Analysis, Protein methods, Tandem Mass Spectrometry methods
- Abstract
Within the field of bioprospecting, disulfide-rich peptides are a promising group of compounds that has the potential to produce important leads for new pharmaceuticals. The disulfide bridges stabilize the tertiary structure of the peptides and often make them superior drug candidates to linear peptides. However, determination of disulfide connectivity in peptides with many disulfide bridges has proven to be laborious and general methods are lacking. This study presents a general approach for structure elucidation of disulfide-rich peptides. The method features sequential reduction and alkylation of a peptide on solid phase combined with sequencing of the fully alkylated peptide by tandem mass spectrometry. Subsequently, the disulfide connectivity is assigned on the basis of the determined alkylation pattern. The presented method is especially suitable for peptides that are prone to disulfide scrambling or are unstable in solution with partly reduced bridges. Additionally, the use of small amounts of peptide in the lowest nmol range makes the method ideal for structure elucidation of unknown peptides from the bioprospecting process. This study successfully demonstrates the new method for seven different peptides with two to four disulfide bridges. Two peptides with previous contradicting publications, μ-conotoxin KIIA and hepcidin-25, are included, and their disulfide connectivity is confirmed in accordance with the latest published results. more...
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- 2016
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18. Biomimetic PVPA in vitro model for estimation of the intestinal drug permeability using fasted and fed state simulated intestinal fluids.
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Naderkhani E, Vasskog T, and Flaten GE
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- Body Fluids chemistry, Body Fluids metabolism, Drug Stability, Fasting metabolism, Fluoresceins metabolism, Humans, Intestinal Absorption, Intestinal Mucosa metabolism, Kinetics, Liposomes, Membranes, Artificial, Phosphorus metabolism, Taurocholic Acid metabolism, Biomimetics, Coated Vesicles chemistry, Phospholipids chemistry
- Abstract
A prerequisite for successful oral drug therapy is the drug's ability to cross the gastrointestinal barrier. Considering the increasing number of new chemical entities in modern drug discovery, reliable and fast in vitro models are required for early and efficient prediction of intestinal permeability. To mimic the intestinal environment, use of biorelevant media may provide valuable information on in vivo drug permeation. The present study aims at improving the novel biomimetic phospholipid vesicle-based permeation assay's (PVPAbiomimetic) biorelevance by investigating the applicability of the biorelevant media; fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF). The FaSSIF and FeSSIF's influence on the permeability of the model drugs acyclovir, indomethacin, griseofulvin and nadolol was then assessed. The barriers' robustness in terms of storage stability was also evaluated. The barriers were found to maintain their integrity in presence of FaSSIF and FeSSIF. The model drugs showed changes in permeability in presence of the different simulated intestinal fluids that were in agreement with previous reports. Moreover, the barrier showed improved storage stability by maintaining its integrity for 6months. Altogether, this study moves the PVPAbiomimetic an important step towards a better in vitro permeability model for use in drug development., (Copyright © 2015 Elsevier B.V. All rights reserved.) more...
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- 2015
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19. Characterization and cytotoxicity studies of the rare 21:4 n-7 acid and other polyunsaturated fatty acids from the marine opisthobranch Scaphander lignarius, isolated using bioassay guided fractionation.
- Author
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Vasskog T, Andersen JH, Hansen E, and Svenson J
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- Animals, Antineoplastic Agents isolation & purification, Antineoplastic Agents toxicity, Arachidonic Acid pharmacology, Biological Assay, Cell Line, Cell Line, Tumor, Chromatography, Liquid, Eicosapentaenoic Acid pharmacology, Fatty Acids, Unsaturated isolation & purification, Fatty Acids, Unsaturated toxicity, Fibroblasts drug effects, Humans, Magnetic Resonance Spectroscopy, Mass Spectrometry, Neoplasms pathology, Antineoplastic Agents pharmacology, Fatty Acids, Unsaturated pharmacology, Mollusca chemistry, Neoplasms drug therapy
- Abstract
The marine opisthobranch Scaphander lignarius has been analyzed in the systematic search for novel bioactive compounds in Arctic marine organisms using bioassay guided fractionation. A number of highly cytotoxic fractions were shown to contain mainly polyunsaturated fatty acids (PUFAs). Selected PUFAs were isolated and identified using both liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). It was shown that the opisthobranch contained unusual PUFAs such as several ω3 fatty acids and the ω7 heneicosa-5,8,11,14-tetraenoic acid (21:4 n-7) not isolated before. The organism was shown to be a very rich source of PUFAs and the activity of the isolated compounds against a range of human cancer cell lines (melanoma, colon carcinoma and breast carcinoma) is further reported. The ω7 PUFA was significantly more cytotoxic in comparison with reference ω6 arachidonic and ω3 eicosapentaenoic acid. A noteworthy non-selective cytotoxicity against normal lung fibroblasts was also established. The paper contains isolation protocols in addition to cytotoxicity data of the isolated compounds. The potential of marine mollusks as a source for rare PUFAs is also discussed. more...
- Published
- 2012
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20. Anaerobic treatment of sewage sludge containing selective serotonin reuptake inhibitors.
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Bergersen O, Hanssen KØ, and Vasskog T
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- Anaerobiosis, Biodegradation, Environmental, Biofuels analysis, Carbon analysis, Molecular Weight, Pharmaceutical Preparations isolation & purification, Selective Serotonin Reuptake Inhibitors isolation & purification, Sewage chemistry, Water Purification methods
- Abstract
The selective serotonin reuptake inhibitors citalopram, sertraline, paroxetine, fluvoxamine and fluoxetine have been investigated in 10 l anaerobic lab-scale digesters with continuous stirring and mesophilic conditions at 37 °C to investigate whether they would be reduced or accumulated in sewage sludge depending on whether the bacteria present were able to use the SSRIs as a carbon source or not. The total SSRI concentration had a significant reduction in concentration during the anaerobic treatment process from theoretically 0.58 mg/l to 0.21 mg/l after 17 days. However, large differences in the reduction of the different compounds were found. Paroxetine and citalopram were found to be almost completely reduced at day 24 with reductions of 85% (citalopram) and 98% (paroxetine). Reductions of 32% (fluoxetine), 53% (fluvoxamine) and 38% (sertraline) indicate that these three compounds have a higher potential for accumulation. None metabolites of these compounds were found in the samples., (Copyright © 2012 Elsevier Ltd. All rights reserved.) more...
- Published
- 2012
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21. In situ formation of nanoparticles upon dispersion of melt extrudate formulations in aqueous medium assessed by asymmetrical flow field-flow fractionation.
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Kanzer J, Hupfeld S, Vasskog T, Tho I, Hölig P, Mägerlein M, Fricker G, and Brandl M
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- Lopinavir, Particle Size, Pyrimidinones chemistry, Ritonavir chemistry, Scattering, Radiation, Solubility, Chemistry, Pharmaceutical methods, Fractionation, Field Flow methods, HIV Protease Inhibitors chemistry, Nanoparticles chemistry
- Abstract
In recent years melt extrudates (e.g. Meltrex) have proven to be a promising formulation tool for poorly water-soluble and poorly bioavailable drugs. During the hot-melt extrusion process solid dispersions are formed. For several of these formulations improved bioavailabilities have been reported; the mechanism behind, however is still not very well understood. The aim of this study was to investigate whether solid dispersions prepared by melt extrusion upon dispersion in aqueous medium form particles and/or supramolecular assemblies. The formulation investigated here contained the human immunodeficiency virus (HIV) protease inhibitors lopinavir and ritonavir, polyvinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64), sorbitan monolaurate (Span((R)) 20) and hydrophilic fumed silica (Aerosil 200). The aqueous dispersions originating from both, API-containing and placebo formulation were investigated using photon correlation spectroscopy (PCS) and asymmetrical flow field-flow fractionation (AsFlFFF) with subsequent online multi-angle light-scattering (MALS) particle size analysis. The content of both APIs in the AsFlFFF-fractions was quantified using high performance liquid chromatography-mass spectrometry. PCS indicated sub-micron particles. AsFlFFF revealed the co-existence of up to three different types of colloidal to nanoparticulate assemblies in the aqueous dispersions. Even though a complete resolution of the composition of the sub-fractions could not be achieved, the following types could be clearly distinguished: The first fraction eluting from AsFlFFF, appears to be colloidal polymer. Only marginal amounts of the APIs were found associated with the polymer. Secondly, API-rich nanoparticles eluted. Thirdly, nanoparticulate assemblies assigned to sorbitan monolaurate and/or hydrophilic fumed silica were identified. A limited amount of drug was found associated with this fraction. Using AsFlFFF-MALS the size of particles in fractions could be determined. From this experience AsFlFFF is regarded as promising technique for investigation of particles/structures originating during dispersion of melt extrudates in aqueous medium in terms of size and type of nanoparticles and their API-content., (Copyright (c) 2010 Elsevier B.V. All rights reserved.) more...
- Published
- 2010
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22. Depletion of selective serotonin reuptake inhibitors during sewage sludge composting.
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Vasskog T, Bergersen O, Anderssen T, Jensen E, and Eggen T
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- Bacteria, Aerobic metabolism, Biodegradation, Environmental, Bioreactors microbiology, Chromatography, High Pressure Liquid, Citalopram analysis, Citalopram metabolism, Fluoxetine analysis, Fluoxetine metabolism, Paroxetine analysis, Paroxetine metabolism, Selective Serotonin Reuptake Inhibitors metabolism, Selective Serotonin Reuptake Inhibitors analysis, Sewage chemistry, Soil Pollutants analysis, Waste Disposal, Fluid methods
- Abstract
Sewage and sewage sludge is known to contain pharmaceuticals, and since sewage sludge is often used as fertilizer within agriculture, the reduction of the selective serotonin reuptake inhibitors (SSRIs) Citalopram, Sertraline, Paroxetine, Fluvoxamine and Fluoxetine during composting has been investigated. Sewage sludge was spiked with the SSRIs before the composting experiment started, and the concentration of the SSRIs in the sludge during a 21 day composting period was measured by liquid phase microextraction (LPME) and high-performance liquid chromatography-mass spectrometry. All the SSRIs had a significant decrease in concentration during the composting process. The highest reduction rates were measured for Fluoxetine and Paroxetine and the lowest for Citalopram. In addition three out of four known SSRI metabolites were found in all the samples, and two of them showed a significant increase in concentration during the composting period. more...
- Published
- 2009
- Full Text
- View/download PDF
23. Hyastatin, a glycine-rich multi-domain antimicrobial peptide isolated from the spider crab (Hyas araneus) hemocytes.
- Author
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Sperstad SV, Haug T, Vasskog T, and Stensvåg K
- Subjects
- Amino Acid Sequence, Animals, Anti-Infective Agents chemistry, Anti-Infective Agents metabolism, Anti-Infective Agents pharmacology, Antimicrobial Cationic Peptides classification, Antimicrobial Cationic Peptides pharmacology, Bacteria drug effects, Bacteria growth & development, Brachyura metabolism, Chromatography, High Pressure Liquid, Cloning, Molecular, DNA, Complementary chemistry, DNA, Complementary genetics, Fungi drug effects, Fungi growth & development, Gene Expression Profiling, Molecular Sequence Data, Peptides classification, Peptides pharmacology, Phylogeny, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Sequence Analysis, Protein, Sequence Homology, Amino Acid, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Antimicrobial Cationic Peptides genetics, Brachyura genetics, Hemocytes metabolism, Peptides genetics
- Abstract
Marine invertebrates are a rich source for the discovery of novel antimicrobial peptides, compounds regarded as important defense components in the host defense system. Here we report the purification and characterization of an 11.7kDa Gly-rich peptide, named hyastatin, from the hemocytes of Hyas araneus. It consists of three distinctly different domains: an N-terminal region enriched in Gly residues, a short Pro/Arg-rich region, and a C-terminal region containing six Cys residues with a Cys pattern resembling the one found in penaeidins. The C-terminus of the mature peptide is presumably amidated. The hyastatin transcript is constitutively expressed and mainly found in hemocytes. Hyastatin shows antimicrobial activity against yeasts, and Gram-positive and Gram-negative bacteria. The N-terminal region, devoid of the Cys-containing region, was recombinantly expressed in Escherichia coli cells, and shows only weak activity against the Gram-positive bacteria Corynebacterium glutamicum. Both hyastatin and the N-terminal region had the ability to bind chitin. Conclusively, this indicates the importance of the Cys-containing region for the antimicrobial activity, and a possible multifunctional character of hyastatin. more...
- Published
- 2009
- Full Text
- View/download PDF
24. Drug permeability across a phospholipid vesicle-based barrier 4. The effect of tensides, co-solvents and pH changes on barrier integrity and on drug permeability.
- Author
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Flaten GE, Luthman K, Vasskog T, and Brandl M
- Subjects
- Caco-2 Cells, Chemical Phenomena, Chemistry, Physical, Electric Impedance, Fluoresceins chemistry, Humans, Hydrogen-Ion Concentration, Membranes, Artificial, Metoprolol administration & dosage, Metoprolol chemistry, Naproxen administration & dosage, Naproxen chemistry, Solvents, Testosterone chemistry, Permeability, Phospholipids chemistry, Surface-Active Agents chemistry
- Abstract
In this study the integrity of the recently developed phospholipid vesicle-based permeability barrier in the presence of a variety of co-solvents and tensides has been investigated. Also included are studies of the influence of these additives on drug permeation and the effect of pH changes on the permeability of ionogenic drug compounds. Permeability experiments using the hydrophilic model compound calcein together with polysorbate 80 (Tween 80), polyoxyl 35 castor oil (Cremophor EL), macrogol lauryl ether (Brij 35), sorbitan monolaurate (Span 20), polyethylene glycol 400 (PEG 400), ethanol and dimethylsulphoxide (DMSO) were performed to determine whether the barriers were affected by the presence of these additives in the donor compartment. It was found that the integrity of the phospholipid vesicle-based barriers did not seem to be influenced by Span 20 up to a concentration of 5mg/ml, PEG 400 up to a concentration of 40mg/ml and ethanol and DMSO up to a concentration of 20mg/ml, respectively. Brij 35, Tween 80 and Cremophor EL were however found to be incompatible with the model at all concentrations as the barriers became leaky. Appearance of phospholipid in the donor chamber in presence of these three tensides indicated that the loss of integrity was due to partial dissolution of the phospholipid vesicles from the barrier. The permeability of testosterone was not significantly improved by the presence of the different co-solvents, except for 40 mg/ml PEG 400 and 20 mg/ml DMSO where the permeability was increased. In the pH study the permeability of metoprolol and naproxen was shown to decrease with increasing degree of ionisation according to the pH partition hypothesis. This renders the permeability model suitable for using pH-shift as a factor to influence solubility of drugs as well as to predict segmental absorption in the gastrointestinal tract. more...
- Published
- 2008
- Full Text
- View/download PDF
25. Occurrence of selective serotonin reuptake inhibitors in sewage and receiving waters at Spitsbergen and in Norway.
- Author
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Vasskog T, Anderssen T, Pedersen-Bjergaard S, Kallenborn R, and Jensen E
- Subjects
- Norway, Sensitivity and Specificity, Selective Serotonin Reuptake Inhibitors chemistry, Selective Serotonin Reuptake Inhibitors isolation & purification, Svalbard, Chromatography, High Pressure Liquid methods, Selective Serotonin Reuptake Inhibitors analysis, Sewage analysis, Spectrometry, Mass, Electrospray Ionization methods, Water analysis
- Abstract
A method for the determination of five selective serotonin reuptake inhibitors (citalopram, sertraline, fluoxetine, fluvoxamine and paroxetine) and four of their metabolites (desmethylcitalopram, didesmethylcitalopram, norfluoxetine and desmethylsertraline) in seawater and sewage influents and effluents, has been developed and validated. The method is based on a three-phase hollow-fibre supported liquid phase microextraction of 1.1L samples, followed by high performance liquid chromatography with electrospray ionization and mass spectrometric detection. The detection limits varied between 17 pg/L (citalopram) and 618 ng/L (desmethylsertraline), and the quantification limits between 57 pg/L (citalopram) and 4.1 ng/L (desmethylsertraline). Sampling was done from February to August in 2007 on three different locations with dissimilarities concerning waste water treatment procedures. No significant difference in SSRI cleansing efficiency between merely sieving (Langnes STP, Tromsø) and a more advanced sewage treatment (VEAS STP, Oslo) was seen. All the investigated compounds are present in all waste water samples from these STPs, and a total concentration of SSRIs and metabolites up to 840 ng/L has been found. Untreated sewage samples have been collected in the small town Longyearbyen at Spitsbergen. Despite few inhabitants (2000), it was still possible to find traces of SSRIs in the waste water. In Tromsø and Longyearbyen the waste water is discharged into the sea, therefore seawater samples have been collected close to the outlets. The results show higher concentrations of SSRIs outside Longyearbyen than Tromsø, possibly due to the stronger tidal currents around Tromsø. However, the concentrations are quite low, not exceeding total concentrations of 3 ng/L. more...
- Published
- 2008
- Full Text
- View/download PDF
26. 25,000-fold pre-concentration in a single step with liquid-phase microextraction.
- Author
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Ho TS, Vasskog T, Anderssen T, Jensen E, Rasmussen KE, and Pedersen-Bjergaard S
- Subjects
- Hydrogen-Ion Concentration, Mass Spectrometry, Spectrophotometry, Ultraviolet, Chromatography, Liquid methods
- Abstract
Hollow fiber protected liquid-phase microextraction (LPME) was developed for large sample volume extractions in a single step, with special emphasis on extraction of basic drugs from environmental waters. Five antidepressant drugs were extracted from 1100 or 100 mL water samples, through approximately 50 microL of dihexyl ether immobilized in the pores in the wall of a porous hollow fiber (liquid membrane), and into 20 microL of 10 mM HCl or HCOOH as the acceptor solution. Extractions were performed for 60 or 120 min supported by magnetic stirring at 800 rpm, and hereafter the acceptor solution was directly injected in HPLC-UV or HPLC-MS. Compared with earlier work on LPME from small sample volumes, both closing the hollow fiber and the type of liquid membrane was found to be critical for large volume extractions. The hollow fibers were carefully closed with a small piece of metal wire, dihexyl ether was used as the liquid membrane, and pH in the sample was adjusted to 11.8 with NaOH. Recoveries from 1100 mL samples were in the range 33-49%, and enrichments were in the range 18,000-27,000 after 120 min of extraction. With HPLC-MS, the drugs were detected down to the 5-30 pg L(-1) level. Within-day precision was within 12.4-20.6% R.S.D. (n=6), whereas between-day precision was within 17.6 and 37.2% R.S.D. Linearity was obtained in the range 1-500 ng L(-1) with r2-values between 0.982 and 0.994. The proposed LPME system was utilized to detect the five antidepressants in wastewater from the city of Tromsø in Northern Norway. more...
- Published
- 2007
- Full Text
- View/download PDF
27. Selective serotonin reuptake inhibitors in sewage influents and effluents from Tromsø, Norway.
- Author
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Vasskog T, Berger U, Samuelsen PJ, Kallenborn R, and Jensen E
- Subjects
- Calibration, Chemical Fractionation, Citalopram analysis, Fluoxetine analysis, Fluvoxamine analysis, Norway, Paroxetine analysis, Sensitivity and Specificity, Sertraline analysis, Chromatography, High Pressure Liquid methods, Selective Serotonin Reuptake Inhibitors analysis, Sewage chemistry, Water Pollutants, Chemical analysis
- Abstract
An analytical method for quantification of the selective serotonin reuptake inhibitors (SSRIs) citalopram, sertraline, paroxetine, fluoxetine and fluvoxamine in sewage influents and effluents from selected sewage treatment plants (STPs) has been developed and validated. This quantification method is based on solid phase extraction of 2.5L samples, followed by liquid-liquid extraction for further sample clean up in order to minimize matrix effects during subsequent quantification. The samples were analysed on a high performance liquid chromatograph coupled to a triple quadrupole mass spectrometric detector using 0.1% ammonia in acetonitrile/water as mobile phase, with positive electrospray ionisation and multiple reaction monitoring for detection and quantification. 1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-pyrrolidine (N-7084) was used as internal standard for quantification. The recovery rates of the SSRIs ranged between 54 and 84%, and the method limit of quantification (MLQ) was between 120 and 290 pg/L for the target compounds. Samples were collected in July 2005 from three different STPs and a pump station in Tromsø, Northern Norway. Two of the STPs serve the University hospital and its psychiatric department, respectively, in addition to domestic sewage. SSRIs were detected in all samples collected. The concentrations varied greatly from below the MLQ to several hundreds ng/L. Concentrations in influents were higher compared to filtered effluents, indicating that SSRIs adsorb to particulate matter, are degraded by microorganisms, or degraded in other ways during the filtration process. However, more samples should be analysed before general conclusions can be drawn. more...
- Published
- 2006
- Full Text
- View/download PDF
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