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- 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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- 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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- 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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- 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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