| 1. |
- Jolkkonen, Mikael, et al.
(författare)
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Kinetic evidence for different mechanisms of interaction of black mamba toxins MT alpha and MT beta with muscarinic receptors
- 2001
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 39:2-3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- By studying the influence of two toxins from the black mamba Dendroaspis polylepis on the kinetics of [H-3]-N-methylscopolamine binding to muscarinic acetylcholine receptors from rat cerebral cortex, it was revealed that these toxins, MT alpha and MT beta, interact with the receptors via kinetically distinct mechanisms. MT beta bound to receptors in a one-step, readily reversible process with the dissociation constant K-d = 5.3 mu M. The binding mechanism of MT alpha was more complex, involving at least two consecutive steps. A fast receptor-toxin complex formation (K-T = 3.8 mu M) was followed by a slow process of isomerisation of this complex (k(i) = 1.8 x 10(-2) s(-1), half-time 39 s). A similar two-step interaction mechanism has been established for a related toxin, MT2 from the green mamba D. angusticeps (K-T = 1.4 mu M, k(i) = 8.3 x 10(-4) s(-1), half-time 840 s). The slow isomerisation process delays the effect of MT alpha and MT2, but increases their apparent potency compared to toxins unable to induce the isomerisation process.
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| 2. |
- Sundell, I.B., et al.
(författare)
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In vitro procoagulant and anticoagulant properties of Naja naja naja venom
- 2003
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 42:3, s. 239-247
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Tidskriftsartikel (refereegranskat)abstract
- Bites by the Indian cobra (Naja naja naja) are common in India and Sri Lanka because of its close association with humans. Cobra venoms are complex and contain several toxic components, including neurotoxins that cause post-synaptic neuromuscular blockade with respiratory paralysis and even death. Bites may also cause extensive local necrosis by mechanisms not fully elucidated. Although no significant coagulopathy has been reported, N.n. naja venom can form blood clots in vitro by activating prothrombin as demonstrated by thrombin-specific chromogenic substrate. Scanning electron microscopy demonstrates that the clots formed by venom lack the thin fibrin strands of normal blood clots formed by thromboplastin or glass contact. Rheometry shows that clots formed by venom have abnormally low elasticity over an extended period and then, as the platelets contract, a retarded and more feeble increase in elasticity. Purified N.n. naja venom PLA2 inhibits platelet aggregation in PRP and explains the decreased clot retraction and retarded and compromised elasticity build up. The present study shows that the PLA 2 and the prothrombin activator from N.n. naja venom have effects on haemostasis and blood clotting, although such effects are not observed systemically in envenomed humans. © 2003 Elsevier Ltd. All rights reserved.
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| 3. |
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| 4. |
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| 5. |
- Lundqvist, Johan, et al.
(författare)
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Microcystins activate nuclear factor erythroid 2-related factor 2 (Nrf2) in human liver cells in vitro - Implications for an oxidative stress induction by microcystins
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 126, s. 47-50
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Tidskriftsartikel (refereegranskat)abstract
- Microcystins, a potential threat to drinking water quality, are hepatotoxic but it has remained unclear if microcystins induce oxidative stress. We investigated if four microcystins could activate the Nrf2 pathway, a regulator of oxidative stress response. Nrf2 activity was significantly increased by microcystin-LR and-RR at 10 mu M, by microcystin-LY at 3 mu M, by [D-Asp3]-LR and by microcystin-LR at 1 mu M. Our results lend support to the suggestion that microcystins may induce oxidative stress response. (C) 2016 Elsevier Ltd. All rights reserved.
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| 6. |
- Malina, Tamás, et al.
(författare)
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Individual variability of venom from the European adder (Vipera berus berus) from one locality in Eastern Hungary
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 135, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- We have revealed intra-population variability among venom samples from several individual European adders (Vipera berus berus) within a defined population in Eastern Hungary. Individual differences in venom pattern were noticed, both gender-specific and age-related, by one-dimensional electrophoresis. Gelatin zymography demonstrated that these individual venoms have different degradation profiles indicating varying protease activity in the specimens from adders of different ages and genders. Some specimens shared a conserved region of substrate degradation, while others had lower or extremely low protease activity. Phospholipase A(2) activity of venoms was similar but not identical. Interspecimen diversity of the venom phospholipase A(2)-spectra (based on the components' molecular masses) was detected by MALDI-TOF MS. The lethal toxicity of venoms (LD50) also showed differences among individual snakes. Extracted venom samples had varying neuromuscular paralysing effect on chick biventer cervicis nerve-muscle preparations. The paralysing effect of venom was lost when calcium in the physiological salt solution was replaced by strontium; indicating that the block of twitch responses to nerve stimulation is associated with the activity of a phospholipase-dependent neurotoxin. In contrast to the studied V.b. berus venoms from different geographical regions so far, this is the first V.b berus population discovered to have predominantly neurotoxic neuromuscular activity. The relevance of varying venom yields is also discussed. This study demonstrates that individual venom variation among V.b. berus living in particular area of Eastern Hungary might contribute to a wider range of clinical manifestations of V.b. hems envenoming than elsewhere in Europe.
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| 7. |
- Persson, Karl-Johan, et al.
(författare)
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Differential tolerance to cyanobacterial exposure between geographically distinct populations of Perca fluviatilis
- 2013
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Ingår i: Toxicon. - : Elsevier. - 0041-0101 .- 1879-3150. ; :76, s. 178-186
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Tidskriftsartikel (refereegranskat)abstract
- Toxic cyanobacterial blooms are an important problem worldwide. Cyanobacteria may negatively impact young-of-the-year (YOY) fish directly (toxin production, turbidity, decrease in water quality) or indirectly (trophic toxin transfer, changes in prey species composition). Here we test whether there are any differences in cyanobacterial tolerance between four geographically distinct populations of European perch (Perca fluviatilis). We show that P. fluviatilis may develop tolerance against cyanobacteria demonstrated by the ability of individuals from a marine site (exposed to annual cyanobacterial blooms) to increase their detoxification more than individuals from an oligotrophic site (rarely exposed to cyanobacteria). Our results also revealed significant interaction effects between genotypes within a population and response to cyanobacterial exposure in terms of absolute growth and detoxification activity. This genotype by treatment interaction may result in local adaptations to cyanobacterial exposure in P. fluviatilis. Hence, the sensitivity against cyanobacterial exposure may differ between within species populations increasing the importance of local management of fish populations.
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| 8. |
- Persson, Karl-Johan, et al.
(författare)
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Effects of the filamentous cyanobacterium Nodularia on fitness and feeding behavior of young-of-the-year (YOY) Eurasian perch (Perca fluviatilis)
- 2011
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 57:7-8, s. 1033-1040
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Tidskriftsartikel (refereegranskat)abstract
- AbstractThis study reveals that both cyanobacterial toxicity and turbidity have the potential to reduce the growth and energy storage of young-of-the-year (YOY) perch and thereby influence survival rates. During the 1990's a reduction in recruitment of YOY perch (Perca fluviatilis) occurred along the Swedish East coast. Concurrently, large blooms of filamentous cyanobacteria have increased in the Baltic Proper and in coastal waters. This study examined whether extended exposure to toxic and non-toxic filamentous cyanobacterium Nodularia affect YOY perch growth and feeding behavior under simulated bloom conditions (30 days at 50 μg Chl a L−1). Specific growth rate (SGR), the somatic condition index (SCI) and the lipid content of YOY perch (10–12 weeks old) were significantly lower in perch exposed to Nodularia compared to fed controls (no Nodularia). YOY perch exposed to non-toxic Nodularia displayed a higher attack rate than perch living in Nodularia free controls in 2 out of 3 trials. Reductions in growth and energy storage, mediated by cyanobacteria, increase the risk of starvation and predation and could locally influence recruitment of YOY perch.Highlights► We investigate the effects of toxic and non-toxic cyanobacterial (Nodularia sp.) on young-of-the-year (YOY) perch (Perca fluviatilis). ► Endpoints are specific growth rate (SGR), lipid content and feeding behavior (feeding and attack rate). ► Results show that both non-toxic and toxic Nodularia reduce SGR and lipid content of YOY perch. ► Reduced growth and energy storage may locally influence recruitment of YOY perch.
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| 9. |
- Rosén, Johan, et al.
(författare)
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A new method for analysis of underivatized free beta-methylamino-alanine : Validation and method comparison
- 2016
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 121, s. 105-108
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Tidskriftsartikel (refereegranskat)abstract
- A new method was developed for analysis of free beta-Methylamino-alanine (BMAA) in biological matrices. The method is based on direct analysis of the underivatized molecule, using an amide column for separation by Hydrophilic Interaction Liquid Chromatography (HILIC) and detection by tandem mass spectrometry (MS/MS) using a deuterium labeled internal standard. The use of Ultra-High Performance Liquid Chromatography (UHPLC) combined with MS/MS detection allowed for high chromatographic resolution and a low limit of detection (0.025 mu g/g wet weight (ww) in mussels). The method was validated by analyzing spiked blank mussels from the Baltic Sea (0.15-4.4 mu g/g (ww), trueness 99%-105%, RSD 2%-8%). An inter-laboratory comparative analysis of extracts of mussel was performed. The mussels were extracted according to an established protocol for analysis of free BMAA, and the extracts were then analyzed in parallel by the new method and a validated procedure based on detection of BMAA derivatized with dansyl chloride. Both methods detected BMAA in similar concentrations. Thus, derivatization with dansyl chloride did not influence the results compared to direct detection. The new method presents an alternative to the commonly applied derivatization step, and is proved through validation and method comparison to reliably identify and quantify free BMAA at low concentration levels.
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| 10. |
- Sousa, Maria Ligia, et al.
(författare)
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Portoamides A and B are mitochondrial toxins and induce cytotoxicity on the proliferative cell layer of in vitro microtumours
- 2020
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Ingår i: Toxicon. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0041-0101 .- 1879-3150. ; 175, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- Cyanobacteria are known to produce many toxins and other secondary metabolites. The study of their specific mode of action may reveal the biotechnological potential of such compounds. Portoamides A and B (PAB) are cyclic peptides isolated from the cyanobacteria Phormidium sp. due to their growth repression effect on microalgae and were shown to be cytotoxic against certain cancer cell lines. In the present work, viability was assessed on HCT116 colon cancer cells grown as monolayer culture and as multicellular spheroids (MTS), non-carcinogenic cells and on zebrafish larvae. HCT116 cells and epithelial RPE-1(hTERT) cells showed very similar degrees of sensitivities to PAB. PAB were able to penetrate the MTS, showing a four-fold high IC50 compared to monolayer cultures. The toxicity of PAB was similar at 4 degrees C and 37 degrees C suggesting energy-independent uptake. PAB exposure decreased ATP production, mitochondrial maximal respiration rates and induced mitochondrial membrane hyperpolarization. PAB induced general organelle stress response, indicated by an increase of the mitochondrial damage sensor PINK-1, and of phosphorylation of eIF2 alpha, characteristic for endoplasmic reticulum stress. In summary, these findings show general toxicity of PAB on immortalized cells, cancer cells and zebrafish embryos, likely due to mitochondrial toxicity.
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| 11. |
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| 12. |
- Strogyloudi, Evangeli, et al.
(författare)
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Estimating the accumulation and transfer of Nodularia spumigena toxins by the blue mussel Mytilus edulis: An appraisal from culture and mesocosm experiments
- 2006
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 48:4, s. 359-372
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of Nodularia spumigena toxins by Mytilus edulis was studied during laboratory and mesocosm experiments in order to investigate the possible pathways of nodularin in mussels and calculate toxin budgets. Mussels were exposed to 0.2-15.6 mu g nodularin 1(-1), fed for up to 5 days with Nodularia cells from culture, or blooming in different nutrient-treated seawater. Toxin concentration was monitored with LC-ESI-MS.During different exposures, the amount of nodularin detected in mussels increased linearly with increasing toxin concentration in food and attained 0.28-13.8 mu g of nodularin g dw(-1) of the mussel whole body tissue after 12h. The digestive gland was found to be the tissue with the highest toxin concentration. Nodularin concentration in faeces was not proportional to faeces production or to toxin concentration in food; however, it seemed to be mostly related to food quality as well as to food availability. The percentage of nodularin taken up by the mussels, relative to the amount contained in the offered food, varied from 10% to 20%, depending on food quality. During a 5-day toxin accumulation experiment, the acute reduction of the toxin in mussel tissues the second day and the following stabilization, showed that probably mussels maintain low toxin levels via efficient elimination and/or toxin metabolism. After a 72 h depuration period, mussels showed 75% reduction in their toxin content.
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| 13. |
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| 14. |
- Turner, Andrew D., et al.
(författare)
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Assessing the presence of marine toxins in bivalve molluscs from southwest India
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 140, s. 147-156
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Elsevier Ltd The south west coast of India has been showing a steady increase in shellfish cultivation both for local consumption and fishery export, over recent years. Perna viridis and Crassostrea madrasensis are two species of bivalve molluscs which grow in some selected regions of southern Karnataka, close to the city of Mangalore. In the early 1980s, shellfish consumers in the region were affected by intoxication from Paralytic Shellfish Poison present in local bivalves (clams and oysters) resulting in hospitalisation of many, including one fatality. Since then, there have been no further reports of serious shellfish intoxication and there is little awareness of the risks from natural toxins and no routine monitoring programme in place to protect shellfish consumers. This study presents the findings from the first ever systematic assessment of the presence of marine toxins in mussels and oysters grown in four different shellfish harvesting areas in the region. Shellfish were collected and subjected to analysis for ASP, PSP and lipophilic toxins, as well as a suite of non-EU regulated toxins such as tetrodotoxin and selected cyclic imines. Results revealed the presence of low levels of PSP toxins in oysters throughout the study period. Overall, total toxicities reached a maximum of 10% of the EU regulatory limit of 800 μg STX eq/kg. Toxin profiles were similar to those reported from the 1980 outbreak. No evidence was found for significant levels of ASP and lipophilic toxins, although some cyclic imines were detected, including gymnodimine. The results indicated that the risk to shellfish consumers during this specific study period would have been low. However, with historical evidence for extremely high levels of PSP toxins in molluscs, there is a strong need for routine surveillance of shellfish production areas for marine toxins, in order to mitigate against human health impacts resulting from unexpected harmful algal blooms, with potentially devastating socio-economic consequences.
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| 15. |
- Westerstrom, Alexander, et al.
(författare)
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Envenoming following bites by the Balkan adder Vipera berus bosniensis - First documented case series from Bulgaria
- 2010
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 56:8, s. 1510-1515
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detailed accounts of bites by the Balkan adder, Vipera bents bosniensis from Bulgaria. Documentation of bites by this subspecies is very rare in the literature and most available accounts are from the northern limit of its distribution. V berus bosniensis is considered to possess neurotoxic venom but little evidence has hitherto been available to support this supposition. In this case series symptoms typical of adder bites developed including oedema, nausea, dizziness, lymphangitis, vomiting, and diarrhoea together with aberrant symptoms such as diplopia and ptosis that confirm the presence of neurotoxic venom in Balkan adders. In addition, unusual and atypical symptoms of adder bites such as painless bites and muscle cramps appeared. The inadequate treatment in hospital and the remote habitats in which this species is encountered are potential sources of complication.
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| 16. |
- Yang, Lei, et al.
(författare)
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Gene expression profiles and molecular mechanism of cultured human chondrocytes' exposure to T-2 toxin and deoxynivalenol
- 2017
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Ingår i: Toxicon. - Amsterdam : Elsevier. - 0041-0101 .- 1879-3150. ; 140, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- T-2 toxin and deoxynivalenol (DON) are secondary metabolites produced by Fusarium fungi and are commonly found on food and feed. Although T-2 toxin and DON have been suggested as the etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, little is known about the mechanism when human chondrocytes are exposed to T-2 toxin and DON. The purpose of this study is to identify the gene expression differences and underlying molecular changes modulated by T-2 toxin and DON in vitro in human chondrocytes. After the experiments of cell viability, the gene expression profiles were analyzed in cells that were treated with 0.01 μg/ml T-2 toxin and 1.0 μg/ml DON for 72 h by Affymetrix Human Gene Chip. The array results showed that 882 and 2118 genes were differentially expressed for T-2 toxin and DON exposure, respectively. Enrichment analysis revealed that diverse cellular processes including DNA damage, cell cycle regulation and metabolism of extracellular matrix were affected when human chondrocytes were exposed to T-2 toxin and DON. These results demonstrate the gene expression differences and molecular mechanism of cultured human chondrocytes exposure to T-2 toxin and DON, and provide a new insight into future research in the etiology of KBD.
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| 17. |
- Brown, Mark A., et al.
(författare)
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Detection of vitamin K-dependent proteins in venoms with a monoclonal antibody specific for gamma-carboxyglutamic acid.
- 2002
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Ingår i: Toxicon. - 0041-0101. ; 40:4, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Carboxyglutamic acid (Gla) is an unusual amino acid that is synthesized post-translationally from glutamate in a vitamin K-dependent reaction. The dicarboxylic side chain of Gla chelates Ca(2+), a property important for the biological activity of vitamin K-dependent proteins. To date, Gla-containing polypeptides have been identified in venom from two groups of organisms: elapid snakes, and snails of the genus Conus. In certain elapid snakes, a gamma-carboxylated coagulation factor Xa-like protein is a component of the venom whereas cone snails utilize Gla in a range of peptide neurotoxins. Using a monoclonal antibody that specifically recognizes Gla residues, venom samples from various organisms were screened by western blotting and immunofluorescence assays. Amino acid analyses were also performed on most samples. A survey of 21 snake species from 12 genera detected gamma-carboxylated polypeptides only in venom of snakes from the elapid subfamily Acanthophiinae. Gla-containing polypeptides were also observed in cone snail venom but not in venom or toxic salivary secretions from several other organisms. The Gla-specific antibody used here provides a simple immunochemical means to detect gamma-carboxylated polypeptides in venom and may allow new species to be identified that utilize Gla in the biosynthesis of toxic polypeptides.
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| 18. |
- Dahlmann, J, et al.
(författare)
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Different methods for toxin analysis in the cyanobacterium Nodularia spumigena (Cyanophyceae)
- 2001
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Ingår i: Toxicon. - 0041-0101. ; 39:8, s. 1183-1190
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The brackish water cyanobacterium Nodularia spumigena produce the hepatotoxic cyclic pentapeptide nodularin. Intoxications for both human as well as animal may arise when water reservoirs are contaminated with potentially toxic Nodularia species. Here, results of three independent methods for the determination of nodularin in different strains of N. spumigena are presented. The results obtained with a protein phosphatase assay and a HPLC/UV/MS method are compared with the results obtained with a bioluminescence assay, which is successfully introduced here for nodularin determination. Statistical evaluation of the three applied methods revealed a good comparability towards the detected toxin content. The methods were evaluated taking into consideration the parameters: handling, efficiency, sensitivity and selectivity. The detection limit in the protein phosphatase assay is highest (0.05 ng nodularin) and lowest (250 ng nodularin) in the bioluminescence assay— it was determined with 5 ng (MS) and 25 ng (UV) for the HPLC/UV/MS methods. The different selectivities and sensitivities are critically discussed and an analytical pathway for the determination of the biotoxin nodularin from Nodularia samples is proposed.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Araujo, S. C. M., et al.
(författare)
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Use of geospatial analyses to address snakebite hotspots in mid-northern Brazil - A direction to health planning in shortfall biodiversity knowledge area
- 2022
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 213, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Knowing the distribution of venomous snakes of medical importance is essential to identify areas at risk for snakebites. Thus, we used an integrative approach based on the application of geographic distribution data of venomous snakes, species distribution modeling (SDM), spatial organization of snakebites, and information on human population density for mapping the potential distribution of snakes and identifying areas at risk of snakebites in the state of Maranhao (mid-northern Brazil). From a compiled database of venomous snake records deposited in biological collections and the literature, we predict the potential distribution of venomous snakes in Maranhao, a state whose diversity and geographic distribution of venomous snake species are poorly known. With this, we constructed potential distribution maps for each venomous snake species with at least one occurrence record within state boundaries, as well as generalized maps by family (Viperidae and Elapidae) and the total number of venomous snakes in Maranhao State. We also obtained data on the number of snakebites recorded in each municipality of Maranhao over a decade (2009-2019) and we ran a Generalized Linear Model to test for relationships between the number of venomous snakebites, the area of occurrence of snakes, and human population density. We obtained 1046 records of venomous snake species for Maranhao, represented by 17 viperid and elapid species. Most of the records were from Viperidae (mostly Bothrops atrox and B. marajoensis) and were concentrated mainly in the Amazon of the northern portion of the state. The models showed accurate predictive performance for all modeled species. The entire area of Maranhao exhibits environmental conditions for the occurrence of venomous snakes, with higher suitability indices in the northern region, in the Amazon rainforest. The number of snakebites was positively correlated with the interaction between high-risk areas (i.e., greater distribution of venomous snakes) and human population density. Our study is a pioneer in using species distribution modeling in mid-northern Brazil to address the scarcity of data on snakebite-causing species, directly contributing to the theme of neglected tropical diseases of the World Health Organization.
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| 24. |
- Bhattacharjee, Payel, 1984, et al.
(författare)
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Aristolochic acid and its derivatives as inhibitors of snake venom L-amino acid oxidase
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 138, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Snake venom L-amino acid oxidase (LAAO) exerts toxicity by inducing hemorrhage, pneumorrhagia, pulmonary edema, cardiac edema, liver cell necrosis etc. Being well conserved, inhibitors of the enzyme may be synthesized using the template of the substrate, substrate binding site and features of the catalytic site of the enzyme. Previous findings showed that aristolochic acid (AA), a major constituent of Aristolochia indica, inhibits Russell's viper venom LAAO enzyme activity since, AA interacts with DNA and causes genotoxicity, derivatives of this compound were synthesized by replacing the nitro group to reduce toxicity while retaining the inhibitory potency. The interactions of AA and its derivatives with LAAO were followed by inhibition kinetics and surface plasmon resonance. Similar interactions with DNA were followed by absorption spectroscopy and atomic force microscopy. LAAO-induced cytotoxicity was evaluated by generation of reactive oxygen species (ROS), cell viability assays, confocal and epifluorescence microscopy. The hydroxyl (AA-OH) and chloro (AA-C1) derivatives acted as inhibitors of LAAO but did not interact with DNA. The derivatives significantly reduced LAAO-induced ROS generation and cytotoxicity in human embryonic kidney (HER 293) and hepatoma (HepG2) cell lines. Confocal images indicated that AA, AA-OH and AA-Cl interfered with the binding of LAAO to the cell membrane. AA-OH and AA-CI significantly inhibited LAAO activity and reduced LAAO-induced cytotoxicity. (C) 2017 Elsevier Ltd. All rights reserved.
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| 25. |
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| 26. |
- Farooq, Harith, 1986, et al.
(författare)
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Snakebite incidence in rural sub-Saharan Africa might be severely underestimated
- 2022
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 219
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Tidskriftsartikel (refereegranskat)abstract
- Snakebites in sub-Saharan Africa account for 20,000 to 32,000 annual deaths. But since most data is retrieved from hospital or incomplete central databases, and many victims do not seek hospital treatment or prefer traditional remedies, the current numbers are likely underestimated. In order to reduce snakebite incidence by 50% by 2030 as targeted by World Health Organization, it is crucial to accurately quantify and understand the current rates of snakebite incidence, which can only be reliably measured through household surveys. In this study, we interviewed 1037 households in nine communities in Cabo Delgado, northern Mozambique. Our aim was to quantify true snakebite incidence and under-reporting, by comparing the total number of snakebites reported to our team during household surveys with the subset of reports that reached health centers. We additionally quantified snakebite incidence in terms of species, location of the attack, type of treatment, season, and gender of the victims. These data allow us to propose conservative extrapolations of snakebite incidence and mortality for the province of Cabo Delgado and for Mozambique. Of all snakebites reported in the surveys (N = 296), most incidents were treated exclusively by traditional doctors (N = 174; 59%) and 25% were not seen by any doctor. Most bites occurred on farms and during the rainy season. Using a conservative estimation where we assume our results to be extrapolatable for the whole of rural Mozambique, but considering snakebites in urban areas to be inexistent, we propose that in Cabo Delgado, every year at least 6124 people are victims of snakebites, of which at least 791 result in deaths. In Mozambique, we extrapolated that every year at least 69,261 people are victims of snakebite, of which at least 8950 result in death (one in eight snakebites is fatal). Our estimates are the first for Mozambique based on data retrieved in the country, and despite being an underestimation they increase snakebite incidence levels ten-fold and the number of deaths by 30-fold. Urgent and widespread surveys are needed to further assess the full extent of snakebites in sub-Saharan Africa, explore regional patterns and develop mitigation plans. © 2022 The Authors
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| 27. |
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| 28. |
- Hansson, Karin M, et al.
(författare)
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Cysteine-rich secretory proteins in snake venoms form high affinity complexes with human and porcine beta-microseminoproteins.
- 2009
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 54, s. 128-137
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Tidskriftsartikel (refereegranskat)abstract
- beta-Microseminoprotein (MSP), a 10kDa protein in human seminal plasma, binds human cysteine-rich secretory protein-3 (CRISP-3) with high affinity. CRISP-3 is a member of the family of CRISPs, which are widespread among animals. In this work we show that human as well as porcine MSP binds catrin, latisemin, pseudecin, and triflin, which are CRISPs present in the venoms of the snakes Crotalus atrox, Laticauda semifasciata, Pseudechis porphyriacus, and Trimeresurus flavoviridis, respectively. The CRISPs were purified from the venoms by affinity chromatography on a human MSP column and their identities were settled by gel electrophoresis and mass spectrometry. Their interactions with human and porcine MSPs were studied with size exclusion chromatography and surface plasmon resonance measurements. The binding affinities at 25 degrees C were between 10(-10)M and 10(-7)M for most of the interactions, with higher affinities for the interactions with porcine MSP compared to human MSP and with Elapidae CRISPs compared to Viperidae CRISPs. The high affinities of the bindings in spite of the differences in amino acid sequence between the MSPs as well as between the CRISPs indicate that the binding is tolerant to amino acid sequence variation and raise the question how universal this cross-species reaction between MSPs and CRISPs is.
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| 29. |
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| 30. |
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| 31. |
- Mussagy, Aidate, et al.
(författare)
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An experimental study of toxin production in Arthrospira fusiformis (Cyanophyceae) isolated from African waters
- 2006
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 48:8, s. 1027-1034
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Tidskriftsartikel (refereegranskat)abstract
- Arthrospira is one genus of cyanoprokaryota for which information on toxin production exists for only a few strains. The purpose of this study was to investigate whether strains of Arthrospira fusiformis produce intracellular toxic compounds such as microcystins and anatoxin-a. The study was based on three strains of Arthrospira, two strains isolated from wastewater ponds in Mozambique and one from Lake Nakuru, Kenya. These strains were cultivated experimentally in different light intensities and salinities. Microcystins were analysed by ELISA and HPLC and anatoxin-a by HPLC. Toxicity analysis of the three strains, following the growth cycle, detected neither microcystins nor anatoxin-a. The results indicated that the strains selected were not toxigenic under the experimental conditions applied. Thus, the strains of A. fusiformis tested in the present study could be considered candidates for use in different applications such as in food supplements and in aquaculture.
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| 32. |
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| 33. |
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| 34. |
- Teneva, I, et al.
(författare)
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Toxic potential of five freshwater Phormidium species (Cyanoprokaryota)
- 2005
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 45:6, s. 711-725
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Tidskriftsartikel (refereegranskat)abstract
- Among the Cyanoprokaryota (blue-green algae), the genus Phormidium has thus far rarely been studied with respect to toxin production and potentially resulting human and environmental health effects. We here show that five previously unexplored freshwater species of this genus (Ph. bijugatum, Ph. molle, Ph. papyraceum, Ph. uncinatum, Ph. autumnale) are indeed capable of producing bioactive compounds. Phormidium extracts caused weight loss as well as neuro/hepatotoxic symptoms in mice, and in the case of Ph. bijugatum even death. Very low levels of saxitoxins and microcystins, as confirmed by ELISA, were insufficient to explain this toxicity and the differing toxic potencies of the Phormidium species. Qualitative HPLC analyses confirmed different substance patterns and in the future could aid in the separation of fractions for more detailed substance characterisation. The results in vivo were confirmed in vitro using cells of human, mouse and fish. The fish cells responded least sensitive but proved useful in studying the temperature dependence of the toxicity by the Phormidium samples. Further, the human cells were more sensitive than the mouse cells thus suggesting that the former may be a more appropriate choice for studying the impact of Phormidium to man. Among the human cells, two cancer cell lines were more responsive to one of the samples than a normal cell line, thereby indicating a potential anti-tumour activity. Thus, the five freshwater Phormidium species should be considered in environmental risk assessment but as well, as a source of therapeutic agents.
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| 35. |
- Torgersen, T., et al.
(författare)
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Profiles and levels of fatty acid esters of okadaic acid group toxins and pectenotoxins during toxin depuration, Part I: Brown crab (Cancer pagurus)
- 2008
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 52:3, s. 407-417
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Tidskriftsartikel (refereegranskat)abstract
- In 2002, two outbreaks of diarrhetic shellfish poisoning (DSP) occurred in Norway, which was later confirmed to be caused by the consumption of brown crab (Cancer pagurus) contaminated predominantly by esters of okadaic acid (OA) after feeding on toxic blue mussels (Mytilus edulis). In addition to OA-group toxins, pectenotoxins (PTXs) are commonly detected in the toxin-producing algae (i.e. Dinophysis). In this paper, an experiment was set up to study the fatty acid ester profiles and depuration rates of OA-group toxins and PTXs from C. pagurus after feeding on M. edulis containing these toxin groups. CA, DTX1, DTX2 and PTX2 SA were all detected primarily in the form of fatty acid esters in the crab hepatopancreas (HP). Crabs preferentially assimilated toxins of the OA group after feeding on the mussels for 1 week. Detailed analysis of the fatty acid ester profile in crabs and mussels showed that the ester profiles in the crabs differed slightly from profiles of the fatty acid esters in M. edulis, but neither ester profile nor ester to free toxin ratio appeared to change in the crabs during the first 2 weeks of deputation. Calculations of deputation rates of the free forms of toxins resulted in similar reduction rates for OA and DTX2, whereas the depuration rate of DTX1, PTX2 and PTX2 SA was considerably faster. From the industrial perspective, the PTX-compounds are of minor importance compared to the OA group toxins in crabs, considering (1) the uncertainty regarding the oral toxicity of the PTXs, (2) the preferential ingestion of OA-group toxins compared to PTXs and (3) the faster depuration of PTXs. (C) 2008 Elsevier Ltd. All rights reserved.
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| 36. |
- Torgersen, T., et al.
(författare)
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Profiles and levels of fatty acid esters of okadaic acid group toxins and pectenotoxins during toxin depuration. Part II: Blue mussels (Mytilus edulis) and flat oyster (Ostrea edulis)
- 2008
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 52:3, s. 418-427
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Tidskriftsartikel (refereegranskat)abstract
- Bivalve molluscs accumulate toxins of the okadaic acid (OA) and pectenotoxin (PTX) groups, which are frequently found in Dinophysis spp. Transformation of the OA-group toxins into fatty acid ester derivatives (often designated "DTX3") is common in many bivalve species but the degree to which these toxins are transformed vary between species, and is also depending on the parent toxin involved. In this paper, detailed profiles and levels of fatty acid esters of OA, DTX1, DTX2 and PTX2 SA were studied in blue mussels (Mytilus edulis) and European flat oysters (Ostrea edulis), collected during a bloom of Dinophysis spp. and after 3 and 6 weeks of depuration. Analysis of samples by HPLC-MS/MS and HPLC-MS2 revealed some differences in identity and abundance of fatty acid moieties of the OA-group esters between species, but the 16:0 fatty acid esters dominated in both oysters and mussels, which is in accordance with the free fatty acid profiles in these species. A wider range of FM SA-esters were detected compared to esters of the CA-group toxins in both mussels and oysters, and in oysters, both 14:0, 18:4 and 20:5 fatty acid side chains were more common than 16:0. OA-group toxins were esterified to a larger degree in oysters (83-93%) compared to mussels (21-41%), and in mussels a higher proportion of OA was esterified compared to DTX1 and DTX2. Contrary to what was observed for CA-group toxins, PTX2 SA was esterified to a larger degree in mussels (81%) compared to oysters (64%). Calculations of depuration rates for all individual esters of each parent compound showed that the esters of DTX1 depurated significantly slower from both mussels and oysters compared to esters of OA, DTX2 and PTX2 SA, but overall the deputation rates of esters of both toxin group were highly similar for both species. This indicated that differences in depuration rates are not causing the large species-specific differences in levels and profiles of these toxins. Instead, the results for the CA-group toxins suggested that a higher rate of esterification in oysters is the main factor causing the observed differences in the proportion of esters to free toxin. For FM SA, large differences in ester profiles and a higher proportion of esters of PTX2 SA in mussels compared to oysters suggested differential assimilation and metabolic rate processes for the PTXs compared to OA-group toxins between these species. Hence, although produced by the same Dinophysis species, conclusions about the dynamics of one toxin group based on results from the other group should be avoided in future studies. (C) 2008 Elsevier Ltd. All rights reserved.
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| 37. |
- Wang, C., et al.
(författare)
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The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells
- 2016
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 115, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Microcystin-leucine arginine (MC-LR) is produced by cyanobacteria and can accumulate in lungs through blood circulation. However, the effect of MC-LR on lung remains unclear. In this study, we investigated the chronic, low-dose effect of MC-LR on mouse lung tissues and the influence of MC-LR on mouse alveolar type II epithelial cells (ATII cells). Methods: MC-LR was orally administered to mice at 0, 1, 10, and 40 mu g/L for 6 consecutive months and mouse lungs were obtained for histopathological and immunoblot analysis. ATII cells were cultured in various concentrations of MC-LR (0, 0.5, 5, 50, 500 nmol/L) for indicated time and the cell viability and proteins change were tested. Results: Our study revealed that the chronic, low-dose MC-LR exposure induced alveolar collapse and lung cell apoptosis as well as the breach of cell junction integrity. Furthermore, following treatment with MC-LR, ATII cells could uptake MC-LR, resulting in apoptosis and disruption of cell junction integrity. Conclusions: These data support the toxic potential of low-dose MC-LR in rendering chronic injury to lung tissues.
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| 38. |
- Wang, X. T., et al.
(författare)
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Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons
- 2016
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101. ; 123, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Microcystin-LR (MC-LR), which generates strong reproductive toxicity, reduces serum testosterone level without directly damaging Leydig cells. The purpose of this study was to identify the target cells of MC-LR in the rat hypothalamic-pituitary axis and to investigate the underlying mechanisms. We found that the gonadotropin-releasing hormone (GnRH) neurons were the direct target of MC-LR. In vivo results showed that upon exposure to rats, cells around the third ventricle of hypothalamus underwent apoptosis. Gnrh1 expression was steadily decreased. The serum levels of GnRH, luteinizing hormone, follicle-stimulating hormone and testosterone showed a similar pattern of early-stage increase and late stage decline. After treatment with MC-LR in immortalized hypothalamic (GTI-7) neurons, increase in cellular Ca2+ and ATP resulted in downregulation of the transcriptional activators Oct-1, Otx-2, Pbxl a and Dlx2, and upregulation of the transcriptional repressor c-Jun, which may mechanistically account for the downregulation of GnRH synthesis. Ca2+ and ATP could also stimulate the release of GnRH, contributing to its unique serum release pattern. (C) 2016 Published by Elsevier Ltd.
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| 39. |
- Wising, Catharina, 1973, et al.
(författare)
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Induction of apoptosis/necrosis in various human cell lineages by Haemophilus ducreyi cytolethal distending toxin.
- 2005
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Ingår i: Toxicon : official journal of the International Society on Toxinology. - : Elsevier BV. - 0041-0101. ; 45:6, s. 767-76
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the impact of highly purified Haemophilus ducreyi cytolethal distending toxin (HdCDT) on the apoptosis and necrosis of various human cells; including myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. The levels of apoptosis and necrosis induced in these cells were compared to those induced by HdCDT in human T cells and in the Jurkat T cell line. Levels of caspase-3 activity were measured, and membrane changes like phosphatidylserine (PS) translocation was evaluated after double-staining with the fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI) using flow cytometry. HdCDT induced various degrees of apoptosis and necrosis in dose- and time-dependent manners in cells of various lineages. Early and late apoptosis (annexin V-stained cells) were induced in more than 90% of T cells and monocytes after treatment with 100 ng/ml HdCDT for 24 and 48 h, respectively. The corresponding numbers for epithelial cells, keratinocytes, and fibroblasts were 26-32% after treatment with 100 ng/ml HdCDT for 48 h. HdCDT appears to eliminate effectively by inducing apoptosis those cells that are involved in immune responses. Epithelial cells, keratinocytes and fibroblasts, which are important for the healing of chancroid ulcers, are eliminated by apoptosis or necrosis after contact with HdCDT, albeit slower and to a lesser extent than T cells.
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| 40. |
- Mullens, Wilfried, et al.
(författare)
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Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC)
- 2024
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
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Tidskriftsartikel (refereegranskat)abstract
- Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.
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