| 1. |
- Johansson, Anders, 1955-
(författare)
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Aggregatibacter actinomycetemcomitans Leukotoxin : a Powerful Tool with Capacity to Cause Imbalance in the Host Inflammatory Response
- 2011
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Ingår i: Toxins. - Basel : MDPI. - 2072-6651. ; 2:3, s. 242-259
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Tidskriftsartikel (refereegranskat)abstract
- Aggregatibacter actinomycetemcomitans has been described as a member of the indigenous oral microbiota of humans, and is involved in the pathology of periodontitis and various non-oral infections. This bacterium selectively kills human leukocytes through expression of leukotoxin, a large pore-forming protein that belongs to the Repeat in Toxin (RTX) family. The specificity of the toxin is related to its prerequisite for a specific target cell receptor, LFA-1, which is solely expressed on leukocytes. The leukotoxin causes death of different leukocyte populations in a variety of ways. It activates a rapid release of lysosomal enzymes and MMPs from neutrophils and causes apoptosis in lymphocytes. In the monocytes/macrophages, the toxin activates caspase-1, a cysteine proteinase, which causes a proinflammatory response by the activation and secretion of IL-1β and IL-18. A specific clone (JP2) of A. actinomycetemcomitans with enhanced leukotoxin expression significantly correlates to disease onset in infected individuals. Taken together, the mechanisms by which this toxin kills leukocytes are closely related to the pathogenic mechanisms of inflammatory disorders, such as periodontitis. Therapeutic strategies targeting the cellular and molecular inflammatory host response in periodontal diseases might be a future treatment alternative
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| 2. |
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| 3. |
- Arund, Jürgen, et al.
(författare)
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Do Only Small Uremic Toxins, Chromophores, Contribute to the Online Dialysis Dose Monitoring by UV Absorbance?
- 2012
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Ingår i: Toxins. - : MDPI AG. - 2072-6651 .- 2072-6651. ; 4:10, s. 849-861
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to evaluate the contributions of the main chromophores to the total UV absorbance of the spent dialysate and to assess removal dynamics of these solutes during optical on-line dialysis dose monitoring. High performance chromatography was used to separate and quantify UV-absorbing solutes in the spent dialysate sampled at the start and at the end of dialysis sessions. Chromatograms were monitored at 210, 254 and 280 nm routinely and full absorption spectra were registered between 200 and 400 nm. Nearly 95% of UV absorbance originates from solutes with high removal ratio, such as uric acid. The contributions of different solute groups vary at different wavelengths and there are dynamical changes in contributions during the single dialysis session. However, large standard deviation of the average contribution values within a series of sessions indicates remarkable differences between individual treatments. A noteworthy contribution of Paracetamol and its metabolites to the total UV absorbance was determined at all three wavelengths. Contribution of slowly dialyzed uremic solutes, such as indoxyl sulfate, was negligible.
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| 4. |
- Behnam-Motlagh, Parviz, et al.
(författare)
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Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy
- 2010
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Ingår i: Toxins. - Basel : MDPI. - 2072-6651. ; 2:10, s. 2467-2477
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Forskningsöversikt (refereegranskat)abstract
- A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co-expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors.
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| 5. |
- Doyle, Siamsa
(författare)
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Light Influences How the Fungal Toxin Deoxynivalenol Affects Plant Cell Death and Defense Responses
- 2014
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Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 6, s. 679-692
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Tidskriftsartikel (refereegranskat)abstract
- The Fusarium mycotoxin deoxynivalenol (DON) can cause cell death in wheat (Triticum aestivum), but can also reduce the level of cell death caused by heat shock in Arabidopsis (Arabidopsis thaliana) cell cultures. We show that 10 mu g mL(-1) DON does not cause cell death in Arabidopsis cell cultures, and its ability to retard heat-induced cell death is light dependent. Under dark conditions, it actually promoted heat-induced cell death. Wheat cultivars differ in their ability to resist this toxin, and we investigated if the ability of wheat to mount defense responses was light dependent. We found no evidence that light affected the transcription of defense genes in DON-treated roots of seedlings of two wheat cultivars, namely cultivar CM82036 that is resistant to DON-induced bleaching of spikelet tissue and cultivar Remus that is not. However, DON treatment of roots led to genotype-dependent and light-enhanced defense transcript accumulation in coleoptiles. Wheat transcripts encoding a phenylalanine ammonia lyase (PAL) gene (previously associated with Fusarium resistance), non-expressor of pathogenesis-related genes-1 (NPR1) and a class III plant peroxidase (POX) were DON-upregulated in coleoptiles of wheat cultivar CM82036 but not of cultivar Remus, and DON-upregulation of these transcripts in cultivar CM82036 was light enhanced. Light and genotype-dependent differences in the DON/DON derivative content of coleoptiles were also observed. These results, coupled with previous findings regarding the effect of DON on plants, show that light either directly or indirectly influences the plant defense responses to DON.
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| 6. |
- Guerra, Lina, et al.
(författare)
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The biology of the cytolethal distending toxins
- 2011
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Ingår i: Toxins. - : MDPI. - 2072-6651 .- 2072-6651. ; 3:3, s. 172-190
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Forskningsöversikt (refereegranskat)abstract
- The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B(2) toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered.
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| 7. |
- Njobeh, P. B., et al.
(författare)
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Estimation of multi-mycotoxin contamination in South African compound feeds
- 2012
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Ingår i: Toxins. - : MDPI AG. - 2072-6651 .- 2072-6651. ; 4:10, s. 836-848
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Tidskriftsartikel (refereegranskat)abstract
- A total of 92 commercial compound feeds from South Africa were investigated for various mycotoxins. The data reveal the highest incidence of feed contamination for fumonisins (FB) (range: 104-2999 μg/kg) followed by deoxynivalenol (DON) (range: 124-2352 μg/kg) and zearalenone (ZEA) (range: 30-610 μg/kg). The incidence of ochratoxin A (OTA) and aflatoxins (AF)-contaminated samples were generally low, i.e., 4% and 30% of samples with levels ranging between 6.4 and 17.1 μg/kg (mean: 9.9 μg/kg) for OTA and 0.2 to 71.8 μg/kg (mean: 9.0 μg/kg) for AF. No samples contained T-2 toxin or HT-2 toxin. However, all samples analyzed were contaminated with at least one mycotoxin with a majority containing several mycotoxins. In particular, 3 of 4 positive samples mainly cattle feeds that had relatively high contents of OTA (ranging from 7 to 17.1 μg/kg) also contained high amounts of AF (>27.5 μg/kg) together with FB, DON and ZEA. Apart from a few samples, the levels of mycotoxins may be regarded as safe for livestock production in South Africa. However, the persistent co-occurrence of mycotoxins in samples, especially those at high concentrations, i.e., AF and OTA, together with other mycotoxins studied, may elicit synergistic or additive effects in animals. This should raise concern as multiple contaminations may pose a risk to livestock production and health.
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| 8. |
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| 9. |
- Stegmayr, Bernd
(författare)
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Uremic Toxins and Lipases in Haemodialysis : A Process of Repeated Metabolic Starvation
- 2014
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Ingår i: Toxins. - : MDPI AG. - 2072-6651 .- 2072-6651. ; 6:5, s. 1505-1511
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Forskningsöversikt (refereegranskat)abstract
- Severe kidney disease results in retention of uremic toxins that inhibit key enzymes for lipid breakdown such as lipoprotein lipase (LPL) and hepatic lipase (HL). For patients in haemodialysis (HD) and peritoneal dialysis (PD) the LPL activity is only about half of that of age and gender matched controls. Angiopoietin, like protein 3 and 4, accumulate in the uremic patients. These factors, therefore, can be considered as uremic toxins. In animal experiments it has been shown that these factors inhibit the LPL activity. To avoid clotting of the dialysis circuit during HD, anticoagulation such as heparin or low molecular weight heparin are added to the patient. Such administration will cause a prompt release of the LPL and HL from its binding sites at the endothelial surface. The liver rapidly degrades the release plasma compound of LPL and HL. This results in a lack of enzyme to degrade triglycerides during the later part of the HD and for another 3-4 h. PD patients have a similar baseline level of lipases but are not exposed to the negative effect of anticoagulation.
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