2016 |
Dinis-Oliveira, R J; Soares, M; Rocha-Pereira, C; Carvalho, F Human and experimental toxicology of orellanine Journal Article Human and Experimental Toxicology, 35 (9), pp. 1016-1029, 2016, (cited By 4). @article{Dinis-Oliveira20161016b, title = {Human and experimental toxicology of orellanine}, author = {R J Dinis-Oliveira and M Soares and C Rocha-Pereira and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979650178&doi=10.1177%2f0960327115613845&partnerID=40&md5=8712c297e0eeb2164cd9b282a0912af4}, doi = {10.1177/0960327115613845}, year = {2016}, date = {2016-01-01}, journal = {Human and Experimental Toxicology}, volume = {35}, number = {9}, pages = {1016-1029}, abstract = {Orellanine is a nephrotoxic toxin produced by some mushroom species of the Cortinarius genus, typically found in Europe and North America. The nephrotoxicity of Cortinarius orellanus is well known and was first recognized in the 1950s when this mushroom was identified as the cause of a mass poisoning in Poland. Typically, onset of symptoms is delayed for 1-2 weeks after ingestion. Some patients suffer mild gastrointestinal discomfort in the latency period before developing signs of renal impairment due to severe interstitial nephritis, acute focal tubular damage, and interstitial fibrosis. There is no specific antidote to orellanine poisoning. The mainstay of treatment is the prevention of secondary complications of kidney failure, adequate dialysis and, in the case of incomplete recovery, management of chronic renal insufficiency. In this work, we aim to review about Cortinarius species, including epidemiological studies, chemical structure, toxicokinetics, toxic doses, mechanisms of toxicity, diagnosis, prognosis, and treatment options. © SAGE Publications.}, note = {cited By 4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Orellanine is a nephrotoxic toxin produced by some mushroom species of the Cortinarius genus, typically found in Europe and North America. The nephrotoxicity of Cortinarius orellanus is well known and was first recognized in the 1950s when this mushroom was identified as the cause of a mass poisoning in Poland. Typically, onset of symptoms is delayed for 1-2 weeks after ingestion. Some patients suffer mild gastrointestinal discomfort in the latency period before developing signs of renal impairment due to severe interstitial nephritis, acute focal tubular damage, and interstitial fibrosis. There is no specific antidote to orellanine poisoning. The mainstay of treatment is the prevention of secondary complications of kidney failure, adequate dialysis and, in the case of incomplete recovery, management of chronic renal insufficiency. In this work, we aim to review about Cortinarius species, including epidemiological studies, chemical structure, toxicokinetics, toxic doses, mechanisms of toxicity, diagnosis, prognosis, and treatment options. © SAGE Publications. |
Faria, J; Barbosa, J; Queirós, O; Moreira, R; Carvalho, F; Dinis-Oliveira, R J Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells Journal Article Toxicology, 359-360 , pp. 1-10, 2016, (cited By 13). @article{Faria20161b, title = {Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells}, author = {J Faria and J Barbosa and O Queirós and R Moreira and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84975527349&doi=10.1016%2fj.tox.2016.06.010&partnerID=40&md5=a639db333f94f63111b694c3edfe2285}, doi = {10.1016/j.tox.2016.06.010}, year = {2016}, date = {2016-01-01}, journal = {Toxicology}, volume = {359-360}, pages = {1-10}, abstract = {Opioid therapy and abuse are increasing, justifying the need to study their toxicity and underlying mechanisms. Given opioid pharmacodynamics at the central nervous system, the analysis of toxic effects in neuronal models gains particular relevance. The aim of this study was to compare the toxicological effects of acute exposure to tramadol and tapentadol in the undifferentiated human SH-SY5Y neuroblastoma cell line. Upon exposure to tramadol and tapentadol concentrations up to 600 μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling. Tapentadol was observed to trigger much more prominent toxic effects than tramadol, ultimately leading to energy deficit and cell death. Cell death was shown to predominantly occur through necrosis, with no alterations in membrane potential or in cytochrome c release. Both drugs were shown to stimulate glucose uptake and to cause ATP depletion, due to changes in the expression of energy metabolism enzymes. The toxicity mechanisms in such a neuronal model are relevant to understand adverse reactions to these opioids and to contribute to dose adjustment in order to avoid neurological damage. © 2016 Elsevier Ireland Ltd}, note = {cited By 13}, keywords = {}, pubstate = {published}, tppubtype = {article} } Opioid therapy and abuse are increasing, justifying the need to study their toxicity and underlying mechanisms. Given opioid pharmacodynamics at the central nervous system, the analysis of toxic effects in neuronal models gains particular relevance. The aim of this study was to compare the toxicological effects of acute exposure to tramadol and tapentadol in the undifferentiated human SH-SY5Y neuroblastoma cell line. Upon exposure to tramadol and tapentadol concentrations up to 600 μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling. Tapentadol was observed to trigger much more prominent toxic effects than tramadol, ultimately leading to energy deficit and cell death. Cell death was shown to predominantly occur through necrosis, with no alterations in membrane potential or in cytochrome c release. Both drugs were shown to stimulate glucose uptake and to cause ATP depletion, due to changes in the expression of energy metabolism enzymes. The toxicity mechanisms in such a neuronal model are relevant to understand adverse reactions to these opioids and to contribute to dose adjustment in order to avoid neurological damage. © 2016 Elsevier Ireland Ltd |
Dinis-Oliveira, R J Oxidative and non-oxidative metabolomics of ethanol Journal Article Current Drug Metabolism, 17 (4), pp. 327-335, 2016, (cited By 19). @article{Dinis-Oliveira2016327b, title = {Oxidative and non-oxidative metabolomics of ethanol}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961754980&doi=10.2174%2f1389200217666160125113806&partnerID=40&md5=8d39ff57a62185e7378477c52b6d5eca}, doi = {10.2174/1389200217666160125113806}, year = {2016}, date = {2016-01-01}, journal = {Current Drug Metabolism}, volume = {17}, number = {4}, pages = {327-335}, abstract = {Background: It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. Objective: This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. Method: An exhaustive literature search was carried out using textual and structural queries for ethanol and related known metabolizing enzymes and metabolites. Results: The main pathway of metabolism is catalyzed by cytosolic alcohol dehydrogenase, which exhibits multiple isoenzymes and genetic polymorphisms with clinical and forensic implications. Another two oxidative routes, the highly inducible CYP2E1 system and peroxisomal catalase may acquire relevance under specific circumstances. In addition to oxidative metabolism, ethanol also originates minor metabolites such as ethyl glucuronide, ethyl sulfate, ethyl phosphate, ethyl nitrite, phosphatidylethanol and fatty acid ethyl esters. These metabolites represent alternative biomarkers since they can be detected several hours or days after ethanol exposure. Conclusion: It is expected that knowing the metabolomics of ethanol may provide additional insights to better understand the toxicological effects and the variability of dose response. © 2016 Bentham Science Publishers.}, note = {cited By 19}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. Objective: This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. Method: An exhaustive literature search was carried out using textual and structural queries for ethanol and related known metabolizing enzymes and metabolites. Results: The main pathway of metabolism is catalyzed by cytosolic alcohol dehydrogenase, which exhibits multiple isoenzymes and genetic polymorphisms with clinical and forensic implications. Another two oxidative routes, the highly inducible CYP2E1 system and peroxisomal catalase may acquire relevance under specific circumstances. In addition to oxidative metabolism, ethanol also originates minor metabolites such as ethyl glucuronide, ethyl sulfate, ethyl phosphate, ethyl nitrite, phosphatidylethanol and fatty acid ethyl esters. These metabolites represent alternative biomarkers since they can be detected several hours or days after ethanol exposure. Conclusion: It is expected that knowing the metabolomics of ethanol may provide additional insights to better understand the toxicological effects and the variability of dose response. © 2016 Bentham Science Publishers. |
Neves, J F; Alves, E A; Soares, J X; Cravo, S M; Silva, A M S; Netto, Pereira A D; Carvalho, F; Dinis-Oliveira, R J; Afonso, C M Data analysis of "krokodil" samples obtained by street-like synthesis Journal Article Data in Brief, 6 , pp. 83-88, 2016, (cited By 5). @article{Neves201683b, title = {Data analysis of "krokodil" samples obtained by street-like synthesis}, author = {J F Neves and E A Alves and J X Soares and S M Cravo and A M S Silva and A D Pereira Netto and F Carvalho and R J Dinis-Oliveira and C M Afonso}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84949035703&doi=10.1016%2fj.dib.2015.11.046&partnerID=40&md5=8b162bca51486b05d81ea4bb70f5d871}, doi = {10.1016/j.dib.2015.11.046}, year = {2016}, date = {2016-01-01}, journal = {Data in Brief}, volume = {6}, pages = {83-88}, abstract = {The data described in this work is related to be the subject of an article in the Forensic Science International, titled: "The harmful chemistry behind "krokodil": street-like synthesis and product analysis" (http://dx.doi.org/10.1016/j.forsciint.2015.07.042) [1]. The data presented here provides additional description of the chemical profile of "krokodil". Physicochemical and organoleptic characteristics, TLC profile, UV/Vis, 1H NMR and FTIR spectrum are presented. These data validate the proposed synthetic procedure and pathway and give further information about the contaminants present in "krokodil". © 2015 The Authors.}, note = {cited By 5}, keywords = {}, pubstate = {published}, tppubtype = {article} } The data described in this work is related to be the subject of an article in the Forensic Science International, titled: "The harmful chemistry behind "krokodil": street-like synthesis and product analysis" (http://dx.doi.org/10.1016/j.forsciint.2015.07.042) [1]. The data presented here provides additional description of the chemical profile of "krokodil". Physicochemical and organoleptic characteristics, TLC profile, UV/Vis, 1H NMR and FTIR spectrum are presented. These data validate the proposed synthetic procedure and pathway and give further information about the contaminants present in "krokodil". © 2015 The Authors. |
Dinis-Oliveira, R J Erratum: Heterogeneous and homogeneous immunoassays for drug analysis (Bioanalysis (2014) 6:21 (2877-2896)) Journal Article Bioanalysis, 8 (3), pp. 253, 2016, (cited By 0). @article{Dinis-Oliveira2016253b, title = {Erratum: Heterogeneous and homogeneous immunoassays for drug analysis (Bioanalysis (2014) 6:21 (2877-2896))}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959048980&doi=10.4155%2fbio.16.1&partnerID=40&md5=a04d1037dcb3b177717cadef17338ca9}, doi = {10.4155/bio.16.1}, year = {2016}, date = {2016-01-01}, journal = {Bioanalysis}, volume = {8}, number = {3}, pages = {253}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dinis-Oliveira, R J Metabolomics of δ9-tetrahydrocannabinol: Implications in toxicity Journal Article Drug Metabolism Reviews, 48 (1), pp. 80-87, 2016, (cited By 14). @article{Dinis-Oliveira201680b, title = {Metabolomics of δ9-tetrahydrocannabinol: Implications in toxicity}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961050997&doi=10.3109%2f03602532.2015.1137307&partnerID=40&md5=d96c2b52d31000bf83946ded03b64dad}, doi = {10.3109/03602532.2015.1137307}, year = {2016}, date = {2016-01-01}, journal = {Drug Metabolism Reviews}, volume = {48}, number = {1}, pages = {80-87}, abstract = {Cannabis sativa is the most commonly used recreational drug, δ9-tetrahydrocannabinol (δ9-THC) being the main addictive compound. Biotransformation of cannabinoids is an important field of xenobiochemistry and toxicology and the study of the metabolism can lead to the discovery of new compounds, unknown metabolites with unique structures and new therapeutic effects. The pharmacokinetics of δ9-THC is dependent on multiple factors such as physical/chemical form, route of administration, genetics, and concurrent consumption of alcohol. This review aims to discuss metabolomics of δ9-THC, namely by presenting all known metabolites of δ9-THC described both in vitro and in vivo, and their roles in the δ9-THC-mediated toxic effects. Since medicinal use is increasing, metabolomics of δ9-THC will also be discussed in order to uncover potential active metabolites that can be made available for this purpose. © 2016 Taylor & Francis.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cannabis sativa is the most commonly used recreational drug, δ9-tetrahydrocannabinol (δ9-THC) being the main addictive compound. Biotransformation of cannabinoids is an important field of xenobiochemistry and toxicology and the study of the metabolism can lead to the discovery of new compounds, unknown metabolites with unique structures and new therapeutic effects. The pharmacokinetics of δ9-THC is dependent on multiple factors such as physical/chemical form, route of administration, genetics, and concurrent consumption of alcohol. This review aims to discuss metabolomics of δ9-THC, namely by presenting all known metabolites of δ9-THC described both in vitro and in vivo, and their roles in the δ9-THC-mediated toxic effects. Since medicinal use is increasing, metabolomics of δ9-THC will also be discussed in order to uncover potential active metabolites that can be made available for this purpose. © 2016 Taylor & Francis. |
Dinis-Oliveira, R J; Magalhães, T The Inherent Drawbacks of the Pressure to Publish in Health Sciences: Good or Bad Science Journal Article F1000Research, 4 , 2016, (cited By 6). @article{Dinis-Oliveira2016n, title = {The Inherent Drawbacks of the Pressure to Publish in Health Sciences: Good or Bad Science}, author = {R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84964603323&doi=10.12688%2ff1000research.6809.2&partnerID=40&md5=128aed89a4d66d9391f6d56eb2e6815f}, doi = {10.12688/f1000research.6809.2}, year = {2016}, date = {2016-01-01}, journal = {F1000Research}, volume = {4}, abstract = {In recent years, there has been a significant increase in the number of scientific publications- it is the era of "hunting the article". This commentary discusses the drawbacks of the pressure to publish that certainly contribute to the 'dark side' of science. In fact, health science career progression greatly relies on the number of scientific publications a researcher has, and in many cases these may be more valorized than the health services provided. Of course, scientific publications help to develop the skills of health care professionals, but as Einstein highlighted " not everything that counts can be counted, and not everything that can be counted counts". © 2016 Dinis-Oliveira RJ and Magalhães T.}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } In recent years, there has been a significant increase in the number of scientific publications- it is the era of "hunting the article". This commentary discusses the drawbacks of the pressure to publish that certainly contribute to the 'dark side' of science. In fact, health science career progression greatly relies on the number of scientific publications a researcher has, and in many cases these may be more valorized than the health services provided. Of course, scientific publications help to develop the skills of health care professionals, but as Einstein highlighted " not everything that counts can be counted, and not everything that can be counted counts". © 2016 Dinis-Oliveira RJ and Magalhães T. |
Dinis-Oliveira, R J; Magalhães, T Teaching and learning based on peer review: A realistic approach in forensic sciences [version 1; referees: 2 approve Journal Article F1000Research, 5 , 2016, (cited By 3). @article{Dinis-Oliveira2016o, title = {Teaching and learning based on peer review: A realistic approach in forensic sciences [version 1; referees: 2 approve}, author = {R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85010976387&doi=10.12688%2fF1000RESEARCH.8726.1&partnerID=40&md5=42b6de103067c3c9e161467db1552af3}, doi = {10.12688/F1000RESEARCH.8726.1}, year = {2016}, date = {2016-01-01}, journal = {F1000Research}, volume = {5}, abstract = {Teaching and learning methods need a continuous upgrade in higher education. However it is also true that some of the modern methodologies do not reduce or prevent school failure. Perhaps the real limitation is the inability to identify the true reasons that may explain it or ignore/undervalue the problem. In our opinion, one of the current constraints of the teaching/learning process is the excess of and inadequate bibliography recommended by the teacher, which results in continuous student difficulties and waste of time in searching and selecting useful information. The need to change the paradigm of the teaching/learning process comes also from employers. They claim forensic experts armed with useful knowledge to face professional life. It is therefore mandatory to identify the new needs and opportunities regarding pedagogical methodologies. This article reflects on the recent importance of peer review in teaching/learning forensic sciences based on the last 10 years of pedagogical experience inseparably from the scientific activity. © 2016 Dinis-Oliveira RJ and Magalhães T.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Teaching and learning methods need a continuous upgrade in higher education. However it is also true that some of the modern methodologies do not reduce or prevent school failure. Perhaps the real limitation is the inability to identify the true reasons that may explain it or ignore/undervalue the problem. In our opinion, one of the current constraints of the teaching/learning process is the excess of and inadequate bibliography recommended by the teacher, which results in continuous student difficulties and waste of time in searching and selecting useful information. The need to change the paradigm of the teaching/learning process comes also from employers. They claim forensic experts armed with useful knowledge to face professional life. It is therefore mandatory to identify the new needs and opportunities regarding pedagogical methodologies. This article reflects on the recent importance of peer review in teaching/learning forensic sciences based on the last 10 years of pedagogical experience inseparably from the scientific activity. © 2016 Dinis-Oliveira RJ and Magalhães T. |
Dinis-Oliveira, R J; Carvalho, F; Costa, I; Silvestre, R; Magalhães, T Response to the comment on "promising blood-derived biomarkers for estimation of the postmortem interval" Journal Article Toxicology Research, 5 (2), pp. 716-718, 2016, (cited By 0). @article{Dinis-Oliveira2016716b, title = {Response to the comment on "promising blood-derived biomarkers for estimation of the postmortem interval"}, author = {R J Dinis-Oliveira and F Carvalho and I Costa and R Silvestre and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959535961&doi=10.1039%2fc5tx00461f&partnerID=40&md5=2f241344341dfe4f4afb906358e9d7f4}, doi = {10.1039/c5tx00461f}, year = {2016}, date = {2016-01-01}, journal = {Toxicology Research}, volume = {5}, number = {2}, pages = {716-718}, abstract = {Following Meurs and Szykuła's comment on our published article titled "Promising blood-derived biomarkers for estimation of the postmortem interval", we recognize the importance of the issues raised, but we would like to emphasize that these contain some misinterpretations and that most of the points were already discussed in depth in our manuscript particularly in the conclusion section. We also aim to highlight further data regarding the difficulties of postmortem interval estimation. © 2016 The Royal Society of Chemistry.}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {article} } Following Meurs and Szykuła's comment on our published article titled "Promising blood-derived biomarkers for estimation of the postmortem interval", we recognize the importance of the issues raised, but we would like to emphasize that these contain some misinterpretations and that most of the points were already discussed in depth in our manuscript particularly in the conclusion section. We also aim to highlight further data regarding the difficulties of postmortem interval estimation. © 2016 The Royal Society of Chemistry. |
2015 |
Dinis-Oliveira, R J Metabolomics of cocaine: Implications in toxicity Journal Article 25 (6), pp. 494-500, 2015, (cited By 9). @article{Dinis-Oliveira2015494, title = {Metabolomics of cocaine: Implications in toxicity}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84942501328&doi=10.3109%2f15376516.2015.1072612&partnerID=40&md5=7c8a73cdfd659c744f666010bc129f9a}, doi = {10.3109/15376516.2015.1072612}, year = {2015}, date = {2015-01-01}, volume = {25}, number = {6}, pages = {494-500}, abstract = {Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects. © 2015 Taylor & Francis.}, note = {cited By 9}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects. © 2015 Taylor & Francis. |
Baltazar, M T; Dinis-Oliveira, R J; Bastos, De Lourdes M; Carvalho, F Paraquat: Molecular mechanisms of neurotoxicity and its relation with autophagy Book 2015, (cited By 0). @book{Baltazar2015159, title = {Paraquat: Molecular mechanisms of neurotoxicity and its relation with autophagy}, author = {M T Baltazar and R J Dinis-Oliveira and M De Lourdes Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84943785668&doi=10.1007%2f978-3-319-13939-5_9&partnerID=40&md5=78b9fdd3afbfa1bd11335f9b03382217}, doi = {10.1007/978-3-319-13939-5_9}, year = {2015}, date = {2015-01-01}, pages = {159-170}, abstract = {Paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) is an effective and widely used herbicide in Asiatic and American countries with a claimed safety record when appropriately applied to eliminate weeds. However, over the last decades a growing body of epidemiologic evidence has been linking longterm/low-dose PQ exposure to the development of Parkinson’s disease (PD). PQ is well known for its ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillation and neuronal cell loss. More recently, more attention has been given to the role of autophagy in several major neurodegenerative diseases and the influence of environmental toxins in this pathway. This chapter provides an overview of the main mechanisms of neurotoxicity of PQ with an emphasis in the autophagic process and its possible relationship to PD. © Springer International Publishing Switzerland 2015.}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {book} } Paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) is an effective and widely used herbicide in Asiatic and American countries with a claimed safety record when appropriately applied to eliminate weeds. However, over the last decades a growing body of epidemiologic evidence has been linking longterm/low-dose PQ exposure to the development of Parkinson’s disease (PD). PQ is well known for its ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillation and neuronal cell loss. More recently, more attention has been given to the role of autophagy in several major neurodegenerative diseases and the influence of environmental toxins in this pathway. This chapter provides an overview of the main mechanisms of neurotoxicity of PQ with an emphasis in the autophagic process and its possible relationship to PD. © Springer International Publishing Switzerland 2015. |
Magalhães, T; Dinis-Oliveira, R J; Silva, B; Corte-Real, F; Vieira, Nuno D Biological Evidence Management for DNA Analysis in Cases of Sexual Assault Journal Article 2015 , 2015, (cited By 2). @article{Magalhães2015, title = {Biological Evidence Management for DNA Analysis in Cases of Sexual Assault}, author = {T Magalhães and R J Dinis-Oliveira and B Silva and F Corte-Real and D Nuno Vieira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84947461280&doi=10.1155%2f2015%2f365674&partnerID=40&md5=72de951ad5c71149c546e57d625d20b0}, doi = {10.1155/2015/365674}, year = {2015}, date = {2015-01-01}, volume = {2015}, abstract = {Biological evidence with forensic interest may be found in several cases of assault, being particularly relevant if sexually related. Sexual assault cases are characterized by low rates of disclosure, reporting, prosecution, and conviction. Biological evidence is sometimes the only way to prove the occurrence of sexual contact and to identify the perpetrator. The major focus of this review is to propose practical approaches and guidelines to help health, forensic, and law enforcement professionals to deal with biological evidence for DNA analysis. Attention should be devoted to avoiding contamination, degradation, and loss of biological evidence, as well as respecting specific measures to properly handle evidence (i.e., selection, collection, packing, sealing, labeling, storage, preservation, transport, and guarantee of the chain custody). Biological evidence must be carefully managed since the relevance of any finding in Forensic Genetics is determined, in the first instance, by the integrity and quantity of the samples submitted for analysis. © 2015 Teresa Magalhães et al.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Biological evidence with forensic interest may be found in several cases of assault, being particularly relevant if sexually related. Sexual assault cases are characterized by low rates of disclosure, reporting, prosecution, and conviction. Biological evidence is sometimes the only way to prove the occurrence of sexual contact and to identify the perpetrator. The major focus of this review is to propose practical approaches and guidelines to help health, forensic, and law enforcement professionals to deal with biological evidence for DNA analysis. Attention should be devoted to avoiding contamination, degradation, and loss of biological evidence, as well as respecting specific measures to properly handle evidence (i.e., selection, collection, packing, sealing, labeling, storage, preservation, transport, and guarantee of the chain custody). Biological evidence must be carefully managed since the relevance of any finding in Forensic Genetics is determined, in the first instance, by the integrity and quantity of the samples submitted for analysis. © 2015 Teresa Magalhães et al. |
Sousa, S; Santos, L; Dinis-Oliveira, R J; Magalhães, T; Santos, A Pedestrian Fatalities Resulting From Train–Person Collisions Journal Article 16 (2), pp. 208-212, 2015, (cited By 2). @article{Sousa2015208, title = {Pedestrian Fatalities Resulting From Train–Person Collisions}, author = {S Sousa and L Santos and R J Dinis-Oliveira and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84922324658&doi=10.1080%2f15389588.2014.914181&partnerID=40&md5=649acb7e07f1a151627526fafcecdef8}, doi = {10.1080/15389588.2014.914181}, year = {2015}, date = {2015-01-01}, volume = {16}, number = {2}, pages = {208-212}, abstract = {Objective: Train–person collisions have a significant impact in our society, due to their negative economic and psychological effects. This work aims to study fatalities resulting from train–person collisions in Portugal. Methods: A retrospective study was conducted based on the analysis of autopsy reports related to train–person fatalities performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences. Results: Suicide was responsible for most of the cases, and males were more often involved in train–person collisions than females. Victims, between 40 and 59 years old, were found to be involved in a high percentage (39%) of the cases, and people older than 65 accounted for a significant percentage (40%) of the accidents. No seasonality was observed in suicide cases, but a decrease in accident numbers was registered in summer. Regarding weekday and time of day, afternoon and non–rush hour were the times when most suicides were observed, whereas accidents did not showed a specific weekday or time of day, except for rush hour, during which they were more frequent. Alcohol-positive blood analysis accounting for 25% of the cases. Conclusions: Differences from other European studies were found, which may be related to the different cultures of the countries/regions, as well as to the differences in the railway systems. More extensive studies must be performed in order to develop strategies to prevent train–person collisions. © 2015, Taylor & Francis Group, LLC.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Objective: Train–person collisions have a significant impact in our society, due to their negative economic and psychological effects. This work aims to study fatalities resulting from train–person collisions in Portugal. Methods: A retrospective study was conducted based on the analysis of autopsy reports related to train–person fatalities performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences. Results: Suicide was responsible for most of the cases, and males were more often involved in train–person collisions than females. Victims, between 40 and 59 years old, were found to be involved in a high percentage (39%) of the cases, and people older than 65 accounted for a significant percentage (40%) of the accidents. No seasonality was observed in suicide cases, but a decrease in accident numbers was registered in summer. Regarding weekday and time of day, afternoon and non–rush hour were the times when most suicides were observed, whereas accidents did not showed a specific weekday or time of day, except for rush hour, during which they were more frequent. Alcohol-positive blood analysis accounting for 25% of the cases. Conclusions: Differences from other European studies were found, which may be related to the different cultures of the countries/regions, as well as to the differences in the railway systems. More extensive studies must be performed in order to develop strategies to prevent train–person collisions. © 2015, Taylor & Francis Group, LLC. |
Mendes, R; Santos, S; Taveira, F; Dinis-Oliveira, R J; Santos, A; Magalhães, T Child Suicide in the North of Portugal Journal Article 60 (2), pp. 471-475, 2015, (cited By 6). @article{Mendes2015471, title = {Child Suicide in the North of Portugal}, author = {R Mendes and S Santos and F Taveira and R J Dinis-Oliveira and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84924278042&doi=10.1111%2f1556-4029.12685&partnerID=40&md5=6a871a0a72186bebf63f4d54122cfbc2}, doi = {10.1111/1556-4029.12685}, year = {2015}, date = {2015-01-01}, volume = {60}, number = {2}, pages = {471-475}, abstract = {Suicide in children is a rare finding and is probably motivated by acts of impulsiveness. This study aims to contribute to the characterization of child suicide in a forensic perspective in the Portuguese population. Data of forensic autopsies from 2004 to 2012 related to suicide victims under 18 years were reviewed. A total of 17 cases, with a male predominance (64.7%) and a mean age of 15.24 ± 1.348 for both genders, were registered. The leading suicide method was hanging (35.3%), and a suicide note was found in 41.2%. Psychological autopsy proved to be useful in promoting a better understanding of these incidents and their antecedents. This study also offers useful information, namely the implied risk factors, for future programs of suicide research and prevention. © 2014 American Academy of Forensic Sciences.}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } Suicide in children is a rare finding and is probably motivated by acts of impulsiveness. This study aims to contribute to the characterization of child suicide in a forensic perspective in the Portuguese population. Data of forensic autopsies from 2004 to 2012 related to suicide victims under 18 years were reviewed. A total of 17 cases, with a male predominance (64.7%) and a mean age of 15.24 ± 1.348 for both genders, were registered. The leading suicide method was hanging (35.3%), and a suicide note was found in 41.2%. Psychological autopsy proved to be useful in promoting a better understanding of these incidents and their antecedents. This study also offers useful information, namely the implied risk factors, for future programs of suicide research and prevention. © 2014 American Academy of Forensic Sciences. |
Costa, I; Carvalho, F; Magalhães, T; Pinho, Guedes De P; Silvestre, R; Dinis-Oliveira, R J Promising blood-derived biomarkers for estimation of the postmortem interval Journal Article 4 (6), pp. 1443-1452, 2015, (cited By 8). @article{Costa20151443, title = {Promising blood-derived biomarkers for estimation of the postmortem interval}, author = {I Costa and F Carvalho and T Magalhães and P Guedes De Pinho and R Silvestre and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945248593&doi=10.1039%2fc5tx00209e&partnerID=40&md5=75f178b133e28b135946710efb25c024}, doi = {10.1039/c5tx00209e}, year = {2015}, date = {2015-01-01}, volume = {4}, number = {6}, pages = {1443-1452}, abstract = {A precise estimation of the postmortem interval (PMI) is one of the most important topics in forensic pathology. However, the PMI estimation is based mainly on the visual observation of cadaverous phenomena (e.g. algor, livor and rigor mortis) and on alternative methods such as thanatochemistry that remain relatively imprecise. The aim of this in vitro study was to evaluate the kinetic alterations of several biochemical parameters (i.e. proteins, enzymes, substrates, electrolytes and lipids) during putrefaction of human blood. For this purpose, we performed kinetic biochemical analysis during a 264 hour period. The results showed a significant linear correlation between total and direct bilirubin, urea, uric acid, transferrin, immunoglobulin M (IgM), creatine kinase (CK), aspartate transaminase (AST), calcium and iron with the time of blood putrefaction. These parameters allowed us to develop two mathematical models that may have predictive values and become important complementary tools of traditional methods to achieve a more accurate PMI estimation. © 2015 The Royal Society of Chemistry.}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } A precise estimation of the postmortem interval (PMI) is one of the most important topics in forensic pathology. However, the PMI estimation is based mainly on the visual observation of cadaverous phenomena (e.g. algor, livor and rigor mortis) and on alternative methods such as thanatochemistry that remain relatively imprecise. The aim of this in vitro study was to evaluate the kinetic alterations of several biochemical parameters (i.e. proteins, enzymes, substrates, electrolytes and lipids) during putrefaction of human blood. For this purpose, we performed kinetic biochemical analysis during a 264 hour period. The results showed a significant linear correlation between total and direct bilirubin, urea, uric acid, transferrin, immunoglobulin M (IgM), creatine kinase (CK), aspartate transaminase (AST), calcium and iron with the time of blood putrefaction. These parameters allowed us to develop two mathematical models that may have predictive values and become important complementary tools of traditional methods to achieve a more accurate PMI estimation. © 2015 The Royal Society of Chemistry. |
Silva, R; Vilas-Boas, V; Carmo, H; Dinis-Oliveira, R J; Carvalho, F; Bastos, De Lourdes M; Remião, F Modulation of P-glycoprotein efflux pump: Induction and activation as a therapeutic strategy Journal Article 149 , pp. 1-123, 2015, (cited By 59). @article{Silva20151, title = {Modulation of P-glycoprotein efflux pump: Induction and activation as a therapeutic strategy}, author = {R Silva and V Vilas-Boas and H Carmo and R J Dinis-Oliveira and F Carvalho and M De Lourdes Bastos and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84925675264&doi=10.1016%2fj.pharmthera.2014.11.013&partnerID=40&md5=80b990e79b4c218b0aaf81c5fd1bcd4d}, doi = {10.1016/j.pharmthera.2014.11.013}, year = {2015}, date = {2015-01-01}, volume = {149}, pages = {1-123}, abstract = {P-glycoprotein (P-gp) is an ATP-dependent efflux pump encoded by the MDR1 gene in humans, known to mediate multidrug resistance of neoplastic cells to cancer therapy. For several decades, P-gp inhibition has drawn many significant research efforts in an attempt to overcome this phenomenon. However, P-gp is also constitutively expressed in normal human epithelial tissues and, due to its broad substrate specificity, to its cellular polarized expression in many excretory and barrier tissues, and to its great efflux capacity, it can play a crucial role in limiting the absorption and distribution of harmful xenobiotics, by decreasing their intracellular accumulation. Such a defense mechanism can be of particular relevance at the intestinal level, by significantly reducing the intestinal absorption of the xenobiotic and, consequently, avoiding its access to the target organs. In this review, the current knowledge on this important efflux pump is summarized, and a new focus is brought on the therapeutic interest of inducing and/or activating P-gp for limiting the toxicity caused by its substrates. Several in vivo and in vitro studies validating the use of such a therapeutic strategy are discussed. An extensive literature search for reported P-gp inducers/activators and for the experimental models used in their characterization was conducted. Those studies demonstrate that effective antidotal pathways can be achieved by efficiently promoting the P-gp-mediated efflux of deleterious xenobiotics, resulting in a significant reduction in their intracellular levels and, consequently, in a significant reduction of their toxicity. © 2014 Elsevier Inc.All rights reserved.}, note = {cited By 59}, keywords = {}, pubstate = {published}, tppubtype = {article} } P-glycoprotein (P-gp) is an ATP-dependent efflux pump encoded by the MDR1 gene in humans, known to mediate multidrug resistance of neoplastic cells to cancer therapy. For several decades, P-gp inhibition has drawn many significant research efforts in an attempt to overcome this phenomenon. However, P-gp is also constitutively expressed in normal human epithelial tissues and, due to its broad substrate specificity, to its cellular polarized expression in many excretory and barrier tissues, and to its great efflux capacity, it can play a crucial role in limiting the absorption and distribution of harmful xenobiotics, by decreasing their intracellular accumulation. Such a defense mechanism can be of particular relevance at the intestinal level, by significantly reducing the intestinal absorption of the xenobiotic and, consequently, avoiding its access to the target organs. In this review, the current knowledge on this important efflux pump is summarized, and a new focus is brought on the therapeutic interest of inducing and/or activating P-gp for limiting the toxicity caused by its substrates. Several in vivo and in vitro studies validating the use of such a therapeutic strategy are discussed. An extensive literature search for reported P-gp inducers/activators and for the experimental models used in their characterization was conducted. Those studies demonstrate that effective antidotal pathways can be achieved by efficiently promoting the P-gp-mediated efflux of deleterious xenobiotics, resulting in a significant reduction in their intracellular levels and, consequently, in a significant reduction of their toxicity. © 2014 Elsevier Inc.All rights reserved. |
Dinis-Oliveira, R J; Magalhães, T; Queirós, O; Proença, J B; Moreira, R; Bastos, M L; Carvalho, F Signs and related mechanisms of ethanol hepatotoxicity Journal Article 8 (2), pp. 86-103, 2015, (cited By 3). @article{Dinis-Oliveira201586, title = {Signs and related mechanisms of ethanol hepatotoxicity}, author = {R J Dinis-Oliveira and T Magalhães and O Queirós and J B Proença and R Moreira and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945418591&partnerID=40&md5=7472dd19efdcec051b05e83d0aa33152}, year = {2015}, date = {2015-01-01}, volume = {8}, number = {2}, pages = {86-103}, abstract = {Ethanol is the most abused psychoactive substance. Accordingly to World Health Organization ethanol ranks among the top five risk factors for disease, disability and death (3.3 million/year) throughout the world. This manuscript highlights and critically analyses clinical and forensic signs related to hepatoxicity of ethanol that may lead to suspected of abuse. Namely, steatosis, jaundice, cirrhosis, hemorrhoids, esophageal varices caput medusae, ascites, petechiae, ecchymoses, splenomegaly, hemochromatosis, xanthelasma, nutritional deficiency, testicular atrophy, gynecomastia and dilated congestive cardiomyopathy are discussed and related to the toxic mechanism of ethanol. © 2015 Bentham Science Publishers.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Ethanol is the most abused psychoactive substance. Accordingly to World Health Organization ethanol ranks among the top five risk factors for disease, disability and death (3.3 million/year) throughout the world. This manuscript highlights and critically analyses clinical and forensic signs related to hepatoxicity of ethanol that may lead to suspected of abuse. Namely, steatosis, jaundice, cirrhosis, hemorrhoids, esophageal varices caput medusae, ascites, petechiae, ecchymoses, splenomegaly, hemochromatosis, xanthelasma, nutritional deficiency, testicular atrophy, gynecomastia and dilated congestive cardiomyopathy are discussed and related to the toxic mechanism of ethanol. © 2015 Bentham Science Publishers. |
Alves, E A; Grund, J P C; Afonso, C M; Netto, A D P; Carvalho, F; Dinis-Oliveira, R J The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity Journal Article 249 , pp. 207-213, 2015, (cited By 17). @article{Alves2015207, title = {The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity}, author = {E A Alves and J P C Grund and C M Afonso and A D P Netto and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84923282607&doi=10.1016%2fj.forsciint.2015.02.001&partnerID=40&md5=ce28f0c27c8279cdc1a333f2180a13bd}, doi = {10.1016/j.forsciint.2015.02.001}, year = {2015}, date = {2015-01-01}, volume = {249}, pages = {207-213}, abstract = {"Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Its use begun in Russia and Ukraine and nowadays is being spread over several other countries. Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil and considered to be responsible for its psychoactive characteristics. The starting materials for desomorphine synthesis are codeine tablets, alkali solutions, organic solvent, acidified water, iodine and red phosphorus, all of which are easily available in retail outlets, such as supermarkets, drugstores, etc. The resulting product is a light brown liquid that is called krokodil. People who inject krokodil present a great variety of serious signs and symptoms, including thrombophlebitis, ulcerations, gangrene, and necrosis, quickly evolving to limb amputation and death. These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis.In this work, we reviewed several aspects of krokodil use, including its epidemiology, pharmacology and the chemical properties of the main active ingredient (desomorphine). To enhance our understanding of the clinical and toxic effects and to support the implementation of harm reduction measures, we also describe the "bathtub chemistry" of krokodil and the content of the final solution. © 2015 Elsevier Ireland Ltd.}, note = {cited By 17}, keywords = {}, pubstate = {published}, tppubtype = {article} } "Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Its use begun in Russia and Ukraine and nowadays is being spread over several other countries. Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil and considered to be responsible for its psychoactive characteristics. The starting materials for desomorphine synthesis are codeine tablets, alkali solutions, organic solvent, acidified water, iodine and red phosphorus, all of which are easily available in retail outlets, such as supermarkets, drugstores, etc. The resulting product is a light brown liquid that is called krokodil. People who inject krokodil present a great variety of serious signs and symptoms, including thrombophlebitis, ulcerations, gangrene, and necrosis, quickly evolving to limb amputation and death. These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis.In this work, we reviewed several aspects of krokodil use, including its epidemiology, pharmacology and the chemical properties of the main active ingredient (desomorphine). To enhance our understanding of the clinical and toxic effects and to support the implementation of harm reduction measures, we also describe the "bathtub chemistry" of krokodil and the content of the final solution. © 2015 Elsevier Ireland Ltd. |
Dinis-Oliveira, R J; Carvalho, F; Moreira, R; Proença, J B; Santos, A; Duarte, J A; Bastos, M D L; Magalhães, T Clinical and forensic signs related to chemical burns: A mechanistic approach Journal Article 41 (4), pp. 658-679, 2015, (cited By 6). @article{Dinis-Oliveira2015658, title = {Clinical and forensic signs related to chemical burns: A mechanistic approach}, author = {R J Dinis-Oliveira and F Carvalho and R Moreira and J B Proença and A Santos and J A Duarte and M D L Bastos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84928824240&doi=10.1016%2fj.burns.2014.09.002&partnerID=40&md5=940ab5715f56738f100b3c1c4c2001d0}, doi = {10.1016/j.burns.2014.09.002}, year = {2015}, date = {2015-01-01}, volume = {41}, number = {4}, pages = {658-679}, abstract = {This manuscript highlights and critically analyses clinical and forensic signs related to chemical burns. Signs that may lead to suspicion of a particular chemical are thoroughly discussed regarding its underlying mechanisms. Burns due to sulfuric, hydrofluoric, nitric, hydrochloric (muriatic) and acetic (including derivatives) acids, hydrogen sulphide, sodium (caustic soda) and calcium (cement) hydroxides, paraquat, burns after inflation and rupture of airbags, povidone-iodine, chlorhexidine/alcohol (in preterm infants), laxatives, and vesicants (warfare agents), will be reviewed since these are the most common agents found in daily practice, for which relevant and timed information may be helpful in formulating an emergency treatment protocols and toxicological analysis. © 2014 Elsevier Ltd and ISBI. All rights reserved.}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } This manuscript highlights and critically analyses clinical and forensic signs related to chemical burns. Signs that may lead to suspicion of a particular chemical are thoroughly discussed regarding its underlying mechanisms. Burns due to sulfuric, hydrofluoric, nitric, hydrochloric (muriatic) and acetic (including derivatives) acids, hydrogen sulphide, sodium (caustic soda) and calcium (cement) hydroxides, paraquat, burns after inflation and rupture of airbags, povidone-iodine, chlorhexidine/alcohol (in preterm infants), laxatives, and vesicants (warfare agents), will be reviewed since these are the most common agents found in daily practice, for which relevant and timed information may be helpful in formulating an emergency treatment protocols and toxicological analysis. © 2014 Elsevier Ltd and ISBI. All rights reserved. |
Appelberg, R; Moreira, D; Barreira-Silva, P; Borges, M; Silva, L; Dinis-Oliveira, R J; Resende, M; Correia-Neves, M; Jordan, M B; Ferreira, N C; Abrunhosa, A J; Silvestre, R The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ Journal Article 145 (4), pp. 498-507, 2015, (cited By 10). @article{Appelberg2015498, title = {The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ}, author = {R Appelberg and D Moreira and P Barreira-Silva and M Borges and L Silva and R J Dinis-Oliveira and M Resende and M Correia-Neves and M B Jordan and N C Ferreira and A J Abrunhosa and R Silvestre}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84936175105&doi=10.1111%2fimm.12464&partnerID=40&md5=4bc3864b4af46a07dbff0d40d7748bf7}, doi = {10.1111/imm.12464}, year = {2015}, date = {2015-01-01}, volume = {145}, number = {4}, pages = {498-507}, abstract = {Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. © 2015 John Wiley & Sons Ltd.}, note = {cited By 10}, keywords = {}, pubstate = {published}, tppubtype = {article} } Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. © 2015 John Wiley & Sons Ltd. |
Barbosa, J.Joana; Faria, J.Juliana; Carvalho, F.Félix; Queiŕs, O.Odília; Moreira, R.Roxana; Dinis-Oliveira, R J Meconium as an alternative matrix in bioanalysis Book 2015, (cited By 0). @book{Barbosa2015139, title = {Meconium as an alternative matrix in bioanalysis}, author = {J.Joana Barbosa and J.Juliana Faria and F.Félix Carvalho and O.Odília Queiŕs and R.Roxana Moreira and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84957356123&doi=10.4155%2ffseb2013.14.114&partnerID=40&md5=f5083b1bf615d4b767116d00decf1170}, doi = {10.4155/fseb2013.14.114}, year = {2015}, date = {2015-01-01}, pages = {139-150}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {book} } |
Gales, L; Amorim, R; Afonso, C M M; Carvalho, F; Dinis-Oliveira, R J Decreasing the toxicity of paraquat through the complexation with sodium salicylate: Stoichiometric analysis Journal Article 336 , pp. 96-98, 2015, (cited By 0). @article{Gales201596, title = {Decreasing the toxicity of paraquat through the complexation with sodium salicylate: Stoichiometric analysis}, author = {L Gales and R Amorim and C M M Afonso and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84940055375&doi=10.1016%2fj.tox.2015.08.005&partnerID=40&md5=e8e1a462f0f2dbcac19c3764d0d97c29}, doi = {10.1016/j.tox.2015.08.005}, year = {2015}, date = {2015-01-01}, volume = {336}, pages = {96-98}, abstract = {Over the last decades, paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) has been involved in numerous fatalities especially attributed to suicide attempts. Previously, it was shown that salicylates, namely sodium salicylate (NaSAL) and lysine acetylsalicylate (LAS) may form complexes with PQ, which may contribute to prevent its toxicity. The direct chemical reactivity between PQ and NaSAL was previously studied by liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry, showing the formation of complexes, though reported data was not fully conclusive. In the present study, the structure of the complex of PQ with NaSAL is fully characterized by crystallography. It was observed that PQ is complexed with 4 NaSAL molecules. Since formulations containing PQ and salicylates have been proposed, these results point that the stoichiometry of 1:4 (PQ:salicylates) should be considered to optimize prevention of PQ-mediated toxic effects. © 2015 Elsevier Ireland Ltd.}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {article} } Over the last decades, paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) has been involved in numerous fatalities especially attributed to suicide attempts. Previously, it was shown that salicylates, namely sodium salicylate (NaSAL) and lysine acetylsalicylate (LAS) may form complexes with PQ, which may contribute to prevent its toxicity. The direct chemical reactivity between PQ and NaSAL was previously studied by liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry, showing the formation of complexes, though reported data was not fully conclusive. In the present study, the structure of the complex of PQ with NaSAL is fully characterized by crystallography. It was observed that PQ is complexed with 4 NaSAL molecules. Since formulations containing PQ and salicylates have been proposed, these results point that the stoichiometry of 1:4 (PQ:salicylates) should be considered to optimize prevention of PQ-mediated toxic effects. © 2015 Elsevier Ireland Ltd. |
Alves, E A; Soares, J X; Afonso, C M; Grund, J P C; Agonia, A S; Cravo, S M; Netto, A D P; Carvalho, F; Dinis-Oliveira, R J The harmful chemistry behind "krokodil": Street-like synthesis and product analysis Journal Article 257 , pp. 76-82, 2015, (cited By 11). @article{Alves201576, title = {The harmful chemistry behind "krokodil": Street-like synthesis and product analysis}, author = {E A Alves and J X Soares and C M Afonso and J P C Grund and A S Agonia and S M Cravo and A D P Netto and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84939533331&doi=10.1016%2fj.forsciint.2015.07.042&partnerID=40&md5=53df0b8f560d2ea95248c06663bcfbb6}, doi = {10.1016/j.forsciint.2015.07.042}, year = {2015}, date = {2015-01-01}, volume = {257}, pages = {76-82}, abstract = {"Krokodil" is the street name for a drug, which has been attracting media and researchers attention due to its increasing spread and extreme toxicity. "Krokodil" is a homemade injectable mixture being used as a cheap substitute for heroin. Its use begun in Russia and Ukraine, but it is being spread throughout other countries. The starting materials for "krokodil" synthesis are tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants and red phosphorus from matchboxes, all of which are easily available in a retail market or drugstores. The resulting product is a light brown liquid that is injected without previous purification. Herein, we aimed to understand the chemistry behind "krokodil" synthesis by mimicking the steps followed by people who use this drug. The successful synthesis was assessed by the presence of desomorphine and other two morphinans. An analytical gas chromatography-electron impact/mass spectrometry (GC-EI/MS) methodology for quantification of desomorphine and codeine was also developed and validated. The methodologies presented herein provide a representative synthesis of "krokodil" street samples and the application of an effective analytical methodology for desomorphine quantification, which was the major morphinan found. Further studies are required in order to find other hypothetical by-products in "krokodil" since these may help to explain signs and symptoms presented by abusers. © 2015 Elsevier Ireland Ltd.}, note = {cited By 11}, keywords = {}, pubstate = {published}, tppubtype = {article} } "Krokodil" is the street name for a drug, which has been attracting media and researchers attention due to its increasing spread and extreme toxicity. "Krokodil" is a homemade injectable mixture being used as a cheap substitute for heroin. Its use begun in Russia and Ukraine, but it is being spread throughout other countries. The starting materials for "krokodil" synthesis are tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants and red phosphorus from matchboxes, all of which are easily available in a retail market or drugstores. The resulting product is a light brown liquid that is injected without previous purification. Herein, we aimed to understand the chemistry behind "krokodil" synthesis by mimicking the steps followed by people who use this drug. The successful synthesis was assessed by the presence of desomorphine and other two morphinans. An analytical gas chromatography-electron impact/mass spectrometry (GC-EI/MS) methodology for quantification of desomorphine and codeine was also developed and validated. The methodologies presented herein provide a representative synthesis of "krokodil" street samples and the application of an effective analytical methodology for desomorphine quantification, which was the major morphinan found. Further studies are required in order to find other hypothetical by-products in "krokodil" since these may help to explain signs and symptoms presented by abusers. © 2015 Elsevier Ireland Ltd. |
Alves, J; Madureira, P; Baltazar, M T; Barros, L; Oliveira, L; Dinis-Oliveira, R J; Andrade, E B; Ribeiro, A; Vieira, L M; Trieu-Cuot, P; Duarte, J A; Carvalho, F; Ferreira, P A safe and stable neonatal vaccine targeting GAPDH confers protection against Group B Streptococcus infections in adult susceptible mice Journal Article 10 (12), 2015, (cited By 3). @article{Alves2015c, title = {A safe and stable neonatal vaccine targeting GAPDH confers protection against Group B Streptococcus infections in adult susceptible mice}, author = {J Alves and P Madureira and M T Baltazar and L Barros and L Oliveira and R J Dinis-Oliveira and E B Andrade and A Ribeiro and L M Vieira and P Trieu-Cuot and J A Duarte and F Carvalho and P Ferreira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84956604014&doi=10.1371%2fjournal.pone.0144196&partnerID=40&md5=1d6543acc2f444bb280009021852215f}, doi = {10.1371/journal.pone.0144196}, year = {2015}, date = {2015-01-01}, volume = {10}, number = {12}, abstract = {Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice © 2015 Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice © 2015 Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Garcia, J; Costa, V M; Carvalho, A T P; Silvestre, R; Duarte, J A; Dourado, D F A R; Arbo, M D; Baltazar, T; Dinis-Oliveira, R J; Baptista, P; de Bastos, Lourdes M; Carvalho, F A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B Journal Article 89 (12), pp. 2305-2323, 2015, (cited By 4). @article{Garcia20152305, title = {A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B}, author = {J Garcia and V M Costa and A T P Carvalho and R Silvestre and J A Duarte and D F A R Dourado and M D Arbo and T Baltazar and R J Dinis-Oliveira and P Baptista and M de Lourdes Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84949323314&doi=10.1007%2fs00204-015-1582-x&partnerID=40&md5=7fcebe247770f6dcd656102c115e15af}, doi = {10.1007/s00204-015-1582-x}, year = {2015}, date = {2015-01-01}, volume = {89}, number = {12}, pages = {2305-2323}, abstract = {Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. α-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to α-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of α-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by α-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal α-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to α-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-α-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with α-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in α-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans. © 2015, Springer-Verlag Berlin Heidelberg.}, note = {cited By 4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. α-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to α-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of α-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by α-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal α-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to α-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-α-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with α-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in α-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans. © 2015, Springer-Verlag Berlin Heidelberg. |
Alves, E A; Soares, J X; Afonso, C M; Grund, J P C; Agonia, A S; Cravo, S M; Netto, A D P; Carvalho, F; Dinis-Oliveira, R J The harmful chemistry behind "krokodil": Street-like synthesis and product analysis Journal Article Forensic Science International, 257 , pp. 76-82, 2015, (cited By 17). @article{Alves201576b, title = {The harmful chemistry behind "krokodil": Street-like synthesis and product analysis}, author = {E A Alves and J X Soares and C M Afonso and J P C Grund and A S Agonia and S M Cravo and A D P Netto and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84939533331&doi=10.1016%2fj.forsciint.2015.07.042&partnerID=40&md5=53df0b8f560d2ea95248c06663bcfbb6}, doi = {10.1016/j.forsciint.2015.07.042}, year = {2015}, date = {2015-01-01}, journal = {Forensic Science International}, volume = {257}, pages = {76-82}, abstract = {"Krokodil" is the street name for a drug, which has been attracting media and researchers attention due to its increasing spread and extreme toxicity. "Krokodil" is a homemade injectable mixture being used as a cheap substitute for heroin. Its use begun in Russia and Ukraine, but it is being spread throughout other countries. The starting materials for "krokodil" synthesis are tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants and red phosphorus from matchboxes, all of which are easily available in a retail market or drugstores. The resulting product is a light brown liquid that is injected without previous purification. Herein, we aimed to understand the chemistry behind "krokodil" synthesis by mimicking the steps followed by people who use this drug. The successful synthesis was assessed by the presence of desomorphine and other two morphinans. An analytical gas chromatography-electron impact/mass spectrometry (GC-EI/MS) methodology for quantification of desomorphine and codeine was also developed and validated. The methodologies presented herein provide a representative synthesis of "krokodil" street samples and the application of an effective analytical methodology for desomorphine quantification, which was the major morphinan found. Further studies are required in order to find other hypothetical by-products in "krokodil" since these may help to explain signs and symptoms presented by abusers. © 2015 Elsevier Ireland Ltd.}, note = {cited By 17}, keywords = {}, pubstate = {published}, tppubtype = {article} } "Krokodil" is the street name for a drug, which has been attracting media and researchers attention due to its increasing spread and extreme toxicity. "Krokodil" is a homemade injectable mixture being used as a cheap substitute for heroin. Its use begun in Russia and Ukraine, but it is being spread throughout other countries. The starting materials for "krokodil" synthesis are tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants and red phosphorus from matchboxes, all of which are easily available in a retail market or drugstores. The resulting product is a light brown liquid that is injected without previous purification. Herein, we aimed to understand the chemistry behind "krokodil" synthesis by mimicking the steps followed by people who use this drug. The successful synthesis was assessed by the presence of desomorphine and other two morphinans. An analytical gas chromatography-electron impact/mass spectrometry (GC-EI/MS) methodology for quantification of desomorphine and codeine was also developed and validated. The methodologies presented herein provide a representative synthesis of "krokodil" street samples and the application of an effective analytical methodology for desomorphine quantification, which was the major morphinan found. Further studies are required in order to find other hypothetical by-products in "krokodil" since these may help to explain signs and symptoms presented by abusers. © 2015 Elsevier Ireland Ltd. |
Garcia, J; Costa, V M; Carvalho, A T P; Silvestre, R; Duarte, J A; Dourado, D F A R; Arbo, M D; Baltazar, T; Dinis-Oliveira, R J; Baptista, P; de Bastos, Lourdes M; Carvalho, F A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B Journal Article Archives of Toxicology, 89 (12), pp. 2305-2323, 2015, (cited By 10). @article{Garcia20152305b, title = {A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B}, author = {J Garcia and V M Costa and A T P Carvalho and R Silvestre and J A Duarte and D F A R Dourado and M D Arbo and T Baltazar and R J Dinis-Oliveira and P Baptista and M de Lourdes Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84949323314&doi=10.1007%2fs00204-015-1582-x&partnerID=40&md5=7fcebe247770f6dcd656102c115e15af}, doi = {10.1007/s00204-015-1582-x}, year = {2015}, date = {2015-01-01}, journal = {Archives of Toxicology}, volume = {89}, number = {12}, pages = {2305-2323}, abstract = {Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. α-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to α-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of α-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by α-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal α-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to α-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-α-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with α-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in α-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans. © 2015, Springer-Verlag Berlin Heidelberg.}, note = {cited By 10}, keywords = {}, pubstate = {published}, tppubtype = {article} } Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. α-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to α-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of α-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by α-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal α-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to α-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-α-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with α-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in α-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans. © 2015, Springer-Verlag Berlin Heidelberg. |
Alves, J; Madureira, P; Baltazar, M T; Barros, L; Oliveira, L; Dinis-Oliveira, R J; Andrade, E B; Ribeiro, A; Vieira, L M; Trieu-Cuot, P; Duarte, J A; Carvalho, F; Ferreira, P A safe and stable neonatal vaccine targeting GAPDH confers protection against Group B Streptococcus infections in adult susceptible mice Journal Article PLoS ONE, 10 (12), 2015, (cited By 7). @article{Alves2015e, title = {A safe and stable neonatal vaccine targeting GAPDH confers protection against Group B Streptococcus infections in adult susceptible mice}, author = {J Alves and P Madureira and M T Baltazar and L Barros and L Oliveira and R J Dinis-Oliveira and E B Andrade and A Ribeiro and L M Vieira and P Trieu-Cuot and J A Duarte and F Carvalho and P Ferreira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84956604014&doi=10.1371%2fjournal.pone.0144196&partnerID=40&md5=1d6543acc2f444bb280009021852215f}, doi = {10.1371/journal.pone.0144196}, year = {2015}, date = {2015-01-01}, journal = {PLoS ONE}, volume = {10}, number = {12}, abstract = {Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice © 2015 Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.}, note = {cited By 7}, keywords = {}, pubstate = {published}, tppubtype = {article} } Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice © 2015 Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Gales, L; Amorim, R; Afonso, C M M; Carvalho, F; Dinis-Oliveira, R J Decreasing the toxicity of paraquat through the complexation with sodium salicylate: Stoichiometric analysis Journal Article Toxicology, 336 , pp. 96-98, 2015, (cited By 1). @article{Gales201596b, title = {Decreasing the toxicity of paraquat through the complexation with sodium salicylate: Stoichiometric analysis}, author = {L Gales and R Amorim and C M M Afonso and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84940055375&doi=10.1016%2fj.tox.2015.08.005&partnerID=40&md5=e8e1a462f0f2dbcac19c3764d0d97c29}, doi = {10.1016/j.tox.2015.08.005}, year = {2015}, date = {2015-01-01}, journal = {Toxicology}, volume = {336}, pages = {96-98}, abstract = {Over the last decades, paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) has been involved in numerous fatalities especially attributed to suicide attempts. Previously, it was shown that salicylates, namely sodium salicylate (NaSAL) and lysine acetylsalicylate (LAS) may form complexes with PQ, which may contribute to prevent its toxicity. The direct chemical reactivity between PQ and NaSAL was previously studied by liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry, showing the formation of complexes, though reported data was not fully conclusive. In the present study, the structure of the complex of PQ with NaSAL is fully characterized by crystallography. It was observed that PQ is complexed with 4 NaSAL molecules. Since formulations containing PQ and salicylates have been proposed, these results point that the stoichiometry of 1:4 (PQ:salicylates) should be considered to optimize prevention of PQ-mediated toxic effects. © 2015 Elsevier Ireland Ltd.}, note = {cited By 1}, keywords = {}, pubstate = {published}, tppubtype = {article} } Over the last decades, paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) has been involved in numerous fatalities especially attributed to suicide attempts. Previously, it was shown that salicylates, namely sodium salicylate (NaSAL) and lysine acetylsalicylate (LAS) may form complexes with PQ, which may contribute to prevent its toxicity. The direct chemical reactivity between PQ and NaSAL was previously studied by liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry, showing the formation of complexes, though reported data was not fully conclusive. In the present study, the structure of the complex of PQ with NaSAL is fully characterized by crystallography. It was observed that PQ is complexed with 4 NaSAL molecules. Since formulations containing PQ and salicylates have been proposed, these results point that the stoichiometry of 1:4 (PQ:salicylates) should be considered to optimize prevention of PQ-mediated toxic effects. © 2015 Elsevier Ireland Ltd. |
Barbosa, J.Joana; Faria, J.Juliana; Carvalho, F.Félix; Queiŕs, O.Odília; Moreira, R.Roxana; Dinis-Oliveira, R J Meconium as an alternative matrix in bioanalysis Book 2015, (cited By 0). @book{Barbosa2015139b, title = {Meconium as an alternative matrix in bioanalysis}, author = {J.Joana Barbosa and J.Juliana Faria and F.Félix Carvalho and O.Odília Queiŕs and R.Roxana Moreira and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84957356123&doi=10.4155%2ffseb2013.14.114&partnerID=40&md5=f5083b1bf615d4b767116d00decf1170}, doi = {10.4155/fseb2013.14.114}, year = {2015}, date = {2015-01-01}, journal = {New Sampling Strategies in Toxicology and Therapeutic Drug Monitoring}, pages = {139-150}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {book} } |
Dinis-Oliveira, R J; Magalhães, T; Queirós, O; Proença, J B; Moreira, R; Bastos, M L; Carvalho, F Signs and related mechanisms of ethanol hepatotoxicity Journal Article Current Drug Abuse Reviews, 8 (2), pp. 86-103, 2015, (cited By 5). @article{Dinis-Oliveira201586b, title = {Signs and related mechanisms of ethanol hepatotoxicity}, author = {R J Dinis-Oliveira and T Magalhães and O Queirós and J B Proença and R Moreira and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945418591&partnerID=40&md5=7472dd19efdcec051b05e83d0aa33152}, year = {2015}, date = {2015-01-01}, journal = {Current Drug Abuse Reviews}, volume = {8}, number = {2}, pages = {86-103}, abstract = {Ethanol is the most abused psychoactive substance. Accordingly to World Health Organization ethanol ranks among the top five risk factors for disease, disability and death (3.3 million/year) throughout the world. This manuscript highlights and critically analyses clinical and forensic signs related to hepatoxicity of ethanol that may lead to suspected of abuse. Namely, steatosis, jaundice, cirrhosis, hemorrhoids, esophageal varices caput medusae, ascites, petechiae, ecchymoses, splenomegaly, hemochromatosis, xanthelasma, nutritional deficiency, testicular atrophy, gynecomastia and dilated congestive cardiomyopathy are discussed and related to the toxic mechanism of ethanol. © 2015 Bentham Science Publishers.}, note = {cited By 5}, keywords = {}, pubstate = {published}, tppubtype = {article} } Ethanol is the most abused psychoactive substance. Accordingly to World Health Organization ethanol ranks among the top five risk factors for disease, disability and death (3.3 million/year) throughout the world. This manuscript highlights and critically analyses clinical and forensic signs related to hepatoxicity of ethanol that may lead to suspected of abuse. Namely, steatosis, jaundice, cirrhosis, hemorrhoids, esophageal varices caput medusae, ascites, petechiae, ecchymoses, splenomegaly, hemochromatosis, xanthelasma, nutritional deficiency, testicular atrophy, gynecomastia and dilated congestive cardiomyopathy are discussed and related to the toxic mechanism of ethanol. © 2015 Bentham Science Publishers. |
Appelberg, R; Moreira, D; Barreira-Silva, P; Borges, M; Silva, L; Dinis-Oliveira, R J; Resende, M; Correia-Neves, M; Jordan, M B; Ferreira, N C; Abrunhosa, A J; Silvestre, R The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ Journal Article Immunology, 145 (4), pp. 498-507, 2015, (cited By 14). @article{Appelberg2015498b, title = {The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ}, author = {R Appelberg and D Moreira and P Barreira-Silva and M Borges and L Silva and R J Dinis-Oliveira and M Resende and M Correia-Neves and M B Jordan and N C Ferreira and A J Abrunhosa and R Silvestre}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84936175105&doi=10.1111%2fimm.12464&partnerID=40&md5=4bc3864b4af46a07dbff0d40d7748bf7}, doi = {10.1111/imm.12464}, year = {2015}, date = {2015-01-01}, journal = {Immunology}, volume = {145}, number = {4}, pages = {498-507}, abstract = {Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. © 2015 John Wiley & Sons Ltd.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. © 2015 John Wiley & Sons Ltd. |
Dinis-Oliveira, R J; Carvalho, F; Moreira, R; Proença, J B; Santos, A; Duarte, J A; Bastos, M D L; Magalhães, T Clinical and forensic signs related to chemical burns: A mechanistic approach Journal Article Burns, 41 (4), pp. 658-679, 2015, (cited By 14). @article{Dinis-Oliveira2015658b, title = {Clinical and forensic signs related to chemical burns: A mechanistic approach}, author = {R J Dinis-Oliveira and F Carvalho and R Moreira and J B Proença and A Santos and J A Duarte and M D L Bastos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84928824240&doi=10.1016%2fj.burns.2014.09.002&partnerID=40&md5=940ab5715f56738f100b3c1c4c2001d0}, doi = {10.1016/j.burns.2014.09.002}, year = {2015}, date = {2015-01-01}, journal = {Burns}, volume = {41}, number = {4}, pages = {658-679}, abstract = {This manuscript highlights and critically analyses clinical and forensic signs related to chemical burns. Signs that may lead to suspicion of a particular chemical are thoroughly discussed regarding its underlying mechanisms. Burns due to sulfuric, hydrofluoric, nitric, hydrochloric (muriatic) and acetic (including derivatives) acids, hydrogen sulphide, sodium (caustic soda) and calcium (cement) hydroxides, paraquat, burns after inflation and rupture of airbags, povidone-iodine, chlorhexidine/alcohol (in preterm infants), laxatives, and vesicants (warfare agents), will be reviewed since these are the most common agents found in daily practice, for which relevant and timed information may be helpful in formulating an emergency treatment protocols and toxicological analysis. © 2014 Elsevier Ltd and ISBI. All rights reserved.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } This manuscript highlights and critically analyses clinical and forensic signs related to chemical burns. Signs that may lead to suspicion of a particular chemical are thoroughly discussed regarding its underlying mechanisms. Burns due to sulfuric, hydrofluoric, nitric, hydrochloric (muriatic) and acetic (including derivatives) acids, hydrogen sulphide, sodium (caustic soda) and calcium (cement) hydroxides, paraquat, burns after inflation and rupture of airbags, povidone-iodine, chlorhexidine/alcohol (in preterm infants), laxatives, and vesicants (warfare agents), will be reviewed since these are the most common agents found in daily practice, for which relevant and timed information may be helpful in formulating an emergency treatment protocols and toxicological analysis. © 2014 Elsevier Ltd and ISBI. All rights reserved. |
Alves, E A; Grund, J P C; Afonso, C M; Netto, A D P; Carvalho, F; Dinis-Oliveira, R J The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity Journal Article Forensic Science International, 249 , pp. 207-213, 2015, (cited By 21). @article{Alves2015207b, title = {The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity}, author = {E A Alves and J P C Grund and C M Afonso and A D P Netto and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84923282607&doi=10.1016%2fj.forsciint.2015.02.001&partnerID=40&md5=ce28f0c27c8279cdc1a333f2180a13bd}, doi = {10.1016/j.forsciint.2015.02.001}, year = {2015}, date = {2015-01-01}, journal = {Forensic Science International}, volume = {249}, pages = {207-213}, abstract = {"Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Its use begun in Russia and Ukraine and nowadays is being spread over several other countries. Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil and considered to be responsible for its psychoactive characteristics. The starting materials for desomorphine synthesis are codeine tablets, alkali solutions, organic solvent, acidified water, iodine and red phosphorus, all of which are easily available in retail outlets, such as supermarkets, drugstores, etc. The resulting product is a light brown liquid that is called krokodil. People who inject krokodil present a great variety of serious signs and symptoms, including thrombophlebitis, ulcerations, gangrene, and necrosis, quickly evolving to limb amputation and death. These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis.In this work, we reviewed several aspects of krokodil use, including its epidemiology, pharmacology and the chemical properties of the main active ingredient (desomorphine). To enhance our understanding of the clinical and toxic effects and to support the implementation of harm reduction measures, we also describe the "bathtub chemistry" of krokodil and the content of the final solution. © 2015 Elsevier Ireland Ltd.}, note = {cited By 21}, keywords = {}, pubstate = {published}, tppubtype = {article} } "Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Its use begun in Russia and Ukraine and nowadays is being spread over several other countries. Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil and considered to be responsible for its psychoactive characteristics. The starting materials for desomorphine synthesis are codeine tablets, alkali solutions, organic solvent, acidified water, iodine and red phosphorus, all of which are easily available in retail outlets, such as supermarkets, drugstores, etc. The resulting product is a light brown liquid that is called krokodil. People who inject krokodil present a great variety of serious signs and symptoms, including thrombophlebitis, ulcerations, gangrene, and necrosis, quickly evolving to limb amputation and death. These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis.In this work, we reviewed several aspects of krokodil use, including its epidemiology, pharmacology and the chemical properties of the main active ingredient (desomorphine). To enhance our understanding of the clinical and toxic effects and to support the implementation of harm reduction measures, we also describe the "bathtub chemistry" of krokodil and the content of the final solution. © 2015 Elsevier Ireland Ltd. |
Dinis-Oliveira, R J Metabolomics of cocaine: Implications in toxicity Journal Article Toxicology Mechanisms and Methods, 25 (6), pp. 494-500, 2015, (cited By 17). @article{Dinis-Oliveira2015494b, title = {Metabolomics of cocaine: Implications in toxicity}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84942501328&doi=10.3109%2f15376516.2015.1072612&partnerID=40&md5=7c8a73cdfd659c744f666010bc129f9a}, doi = {10.3109/15376516.2015.1072612}, year = {2015}, date = {2015-01-01}, journal = {Toxicology Mechanisms and Methods}, volume = {25}, number = {6}, pages = {494-500}, abstract = {Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects. © 2015 Taylor & Francis.}, note = {cited By 17}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects. © 2015 Taylor & Francis. |
Baltazar, M T; Dinis-Oliveira, R J; Bastos, De Lourdes M; Carvalho, F Paraquat: Molecular mechanisms of neurotoxicity and its relation with autophagy Book 2015, (cited By 1). @book{Baltazar2015159b, title = {Paraquat: Molecular mechanisms of neurotoxicity and its relation with autophagy}, author = {M T Baltazar and R J Dinis-Oliveira and M De Lourdes Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84943785668&doi=10.1007%2f978-3-319-13939-5_9&partnerID=40&md5=78b9fdd3afbfa1bd11335f9b03382217}, doi = {10.1007/978-3-319-13939-5_9}, year = {2015}, date = {2015-01-01}, journal = {Toxicity and Autophagy in Neurodegenerative Disorders}, pages = {159-170}, abstract = {Paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) is an effective and widely used herbicide in Asiatic and American countries with a claimed safety record when appropriately applied to eliminate weeds. However, over the last decades a growing body of epidemiologic evidence has been linking longterm/low-dose PQ exposure to the development of Parkinson’s disease (PD). PQ is well known for its ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillation and neuronal cell loss. More recently, more attention has been given to the role of autophagy in several major neurodegenerative diseases and the influence of environmental toxins in this pathway. This chapter provides an overview of the main mechanisms of neurotoxicity of PQ with an emphasis in the autophagic process and its possible relationship to PD. © Springer International Publishing Switzerland 2015.}, note = {cited By 1}, keywords = {}, pubstate = {published}, tppubtype = {book} } Paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) is an effective and widely used herbicide in Asiatic and American countries with a claimed safety record when appropriately applied to eliminate weeds. However, over the last decades a growing body of epidemiologic evidence has been linking longterm/low-dose PQ exposure to the development of Parkinson’s disease (PD). PQ is well known for its ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillation and neuronal cell loss. More recently, more attention has been given to the role of autophagy in several major neurodegenerative diseases and the influence of environmental toxins in this pathway. This chapter provides an overview of the main mechanisms of neurotoxicity of PQ with an emphasis in the autophagic process and its possible relationship to PD. © Springer International Publishing Switzerland 2015. |
Magalhães, T; Dinis-Oliveira, R J; Silva, B; Corte-Real, F; Vieira, Nuno D Biological Evidence Management for DNA Analysis in Cases of Sexual Assault Journal Article Scientific World Journal, 2015 , 2015, (cited By 8). @article{Magalhães2015b, title = {Biological Evidence Management for DNA Analysis in Cases of Sexual Assault}, author = {T Magalhães and R J Dinis-Oliveira and B Silva and F Corte-Real and D Nuno Vieira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84947461280&doi=10.1155%2f2015%2f365674&partnerID=40&md5=72de951ad5c71149c546e57d625d20b0}, doi = {10.1155/2015/365674}, year = {2015}, date = {2015-01-01}, journal = {Scientific World Journal}, volume = {2015}, abstract = {Biological evidence with forensic interest may be found in several cases of assault, being particularly relevant if sexually related. Sexual assault cases are characterized by low rates of disclosure, reporting, prosecution, and conviction. Biological evidence is sometimes the only way to prove the occurrence of sexual contact and to identify the perpetrator. The major focus of this review is to propose practical approaches and guidelines to help health, forensic, and law enforcement professionals to deal with biological evidence for DNA analysis. Attention should be devoted to avoiding contamination, degradation, and loss of biological evidence, as well as respecting specific measures to properly handle evidence (i.e., selection, collection, packing, sealing, labeling, storage, preservation, transport, and guarantee of the chain custody). Biological evidence must be carefully managed since the relevance of any finding in Forensic Genetics is determined, in the first instance, by the integrity and quantity of the samples submitted for analysis. © 2015 Teresa Magalhães et al.}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } Biological evidence with forensic interest may be found in several cases of assault, being particularly relevant if sexually related. Sexual assault cases are characterized by low rates of disclosure, reporting, prosecution, and conviction. Biological evidence is sometimes the only way to prove the occurrence of sexual contact and to identify the perpetrator. The major focus of this review is to propose practical approaches and guidelines to help health, forensic, and law enforcement professionals to deal with biological evidence for DNA analysis. Attention should be devoted to avoiding contamination, degradation, and loss of biological evidence, as well as respecting specific measures to properly handle evidence (i.e., selection, collection, packing, sealing, labeling, storage, preservation, transport, and guarantee of the chain custody). Biological evidence must be carefully managed since the relevance of any finding in Forensic Genetics is determined, in the first instance, by the integrity and quantity of the samples submitted for analysis. © 2015 Teresa Magalhães et al. |
Sousa, S; Santos, L; Dinis-Oliveira, R J; Magalhães, T; Santos, A Pedestrian Fatalities Resulting From Train–Person Collisions Journal Article Traffic Injury Prevention, 16 (2), pp. 208-212, 2015, (cited By 2). @article{Sousa2015208b, title = {Pedestrian Fatalities Resulting From Train–Person Collisions}, author = {S Sousa and L Santos and R J Dinis-Oliveira and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84922324658&doi=10.1080%2f15389588.2014.914181&partnerID=40&md5=649acb7e07f1a151627526fafcecdef8}, doi = {10.1080/15389588.2014.914181}, year = {2015}, date = {2015-01-01}, journal = {Traffic Injury Prevention}, volume = {16}, number = {2}, pages = {208-212}, abstract = {Objective: Train–person collisions have a significant impact in our society, due to their negative economic and psychological effects. This work aims to study fatalities resulting from train–person collisions in Portugal. Methods: A retrospective study was conducted based on the analysis of autopsy reports related to train–person fatalities performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences. Results: Suicide was responsible for most of the cases, and males were more often involved in train–person collisions than females. Victims, between 40 and 59 years old, were found to be involved in a high percentage (39%) of the cases, and people older than 65 accounted for a significant percentage (40%) of the accidents. No seasonality was observed in suicide cases, but a decrease in accident numbers was registered in summer. Regarding weekday and time of day, afternoon and non–rush hour were the times when most suicides were observed, whereas accidents did not showed a specific weekday or time of day, except for rush hour, during which they were more frequent. Alcohol-positive blood analysis accounting for 25% of the cases. Conclusions: Differences from other European studies were found, which may be related to the different cultures of the countries/regions, as well as to the differences in the railway systems. More extensive studies must be performed in order to develop strategies to prevent train–person collisions. © 2015, Taylor & Francis Group, LLC.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Objective: Train–person collisions have a significant impact in our society, due to their negative economic and psychological effects. This work aims to study fatalities resulting from train–person collisions in Portugal. Methods: A retrospective study was conducted based on the analysis of autopsy reports related to train–person fatalities performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences. Results: Suicide was responsible for most of the cases, and males were more often involved in train–person collisions than females. Victims, between 40 and 59 years old, were found to be involved in a high percentage (39%) of the cases, and people older than 65 accounted for a significant percentage (40%) of the accidents. No seasonality was observed in suicide cases, but a decrease in accident numbers was registered in summer. Regarding weekday and time of day, afternoon and non–rush hour were the times when most suicides were observed, whereas accidents did not showed a specific weekday or time of day, except for rush hour, during which they were more frequent. Alcohol-positive blood analysis accounting for 25% of the cases. Conclusions: Differences from other European studies were found, which may be related to the different cultures of the countries/regions, as well as to the differences in the railway systems. More extensive studies must be performed in order to develop strategies to prevent train–person collisions. © 2015, Taylor & Francis Group, LLC. |
Silva, R; Vilas-Boas, V; Carmo, H; Dinis-Oliveira, R J; Carvalho, F; Bastos, De Lourdes M; Remião, F Modulation of P-glycoprotein efflux pump: Induction and activation as a therapeutic strategy Journal Article Pharmacology and Therapeutics, 149 , pp. 1-123, 2015, (cited By 93). @article{Silva20151b, title = {Modulation of P-glycoprotein efflux pump: Induction and activation as a therapeutic strategy}, author = {R Silva and V Vilas-Boas and H Carmo and R J Dinis-Oliveira and F Carvalho and M De Lourdes Bastos and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84925675264&doi=10.1016%2fj.pharmthera.2014.11.013&partnerID=40&md5=80b990e79b4c218b0aaf81c5fd1bcd4d}, doi = {10.1016/j.pharmthera.2014.11.013}, year = {2015}, date = {2015-01-01}, journal = {Pharmacology and Therapeutics}, volume = {149}, pages = {1-123}, abstract = {P-glycoprotein (P-gp) is an ATP-dependent efflux pump encoded by the MDR1 gene in humans, known to mediate multidrug resistance of neoplastic cells to cancer therapy. For several decades, P-gp inhibition has drawn many significant research efforts in an attempt to overcome this phenomenon. However, P-gp is also constitutively expressed in normal human epithelial tissues and, due to its broad substrate specificity, to its cellular polarized expression in many excretory and barrier tissues, and to its great efflux capacity, it can play a crucial role in limiting the absorption and distribution of harmful xenobiotics, by decreasing their intracellular accumulation. Such a defense mechanism can be of particular relevance at the intestinal level, by significantly reducing the intestinal absorption of the xenobiotic and, consequently, avoiding its access to the target organs. In this review, the current knowledge on this important efflux pump is summarized, and a new focus is brought on the therapeutic interest of inducing and/or activating P-gp for limiting the toxicity caused by its substrates. Several in vivo and in vitro studies validating the use of such a therapeutic strategy are discussed. An extensive literature search for reported P-gp inducers/activators and for the experimental models used in their characterization was conducted. Those studies demonstrate that effective antidotal pathways can be achieved by efficiently promoting the P-gp-mediated efflux of deleterious xenobiotics, resulting in a significant reduction in their intracellular levels and, consequently, in a significant reduction of their toxicity. © 2014 Elsevier Inc.All rights reserved.}, note = {cited By 93}, keywords = {}, pubstate = {published}, tppubtype = {article} } P-glycoprotein (P-gp) is an ATP-dependent efflux pump encoded by the MDR1 gene in humans, known to mediate multidrug resistance of neoplastic cells to cancer therapy. For several decades, P-gp inhibition has drawn many significant research efforts in an attempt to overcome this phenomenon. However, P-gp is also constitutively expressed in normal human epithelial tissues and, due to its broad substrate specificity, to its cellular polarized expression in many excretory and barrier tissues, and to its great efflux capacity, it can play a crucial role in limiting the absorption and distribution of harmful xenobiotics, by decreasing their intracellular accumulation. Such a defense mechanism can be of particular relevance at the intestinal level, by significantly reducing the intestinal absorption of the xenobiotic and, consequently, avoiding its access to the target organs. In this review, the current knowledge on this important efflux pump is summarized, and a new focus is brought on the therapeutic interest of inducing and/or activating P-gp for limiting the toxicity caused by its substrates. Several in vivo and in vitro studies validating the use of such a therapeutic strategy are discussed. An extensive literature search for reported P-gp inducers/activators and for the experimental models used in their characterization was conducted. Those studies demonstrate that effective antidotal pathways can be achieved by efficiently promoting the P-gp-mediated efflux of deleterious xenobiotics, resulting in a significant reduction in their intracellular levels and, consequently, in a significant reduction of their toxicity. © 2014 Elsevier Inc.All rights reserved. |
Costa, I; Carvalho, F; Magalhães, T; Pinho, Guedes De P; Silvestre, R; Dinis-Oliveira, R J Promising blood-derived biomarkers for estimation of the postmortem interval Journal Article Toxicology Research, 4 (6), pp. 1443-1452, 2015, (cited By 12). @article{Costa20151443b, title = {Promising blood-derived biomarkers for estimation of the postmortem interval}, author = {I Costa and F Carvalho and T Magalhães and P Guedes De Pinho and R Silvestre and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945248593&doi=10.1039%2fc5tx00209e&partnerID=40&md5=75f178b133e28b135946710efb25c024}, doi = {10.1039/c5tx00209e}, year = {2015}, date = {2015-01-01}, journal = {Toxicology Research}, volume = {4}, number = {6}, pages = {1443-1452}, abstract = {A precise estimation of the postmortem interval (PMI) is one of the most important topics in forensic pathology. However, the PMI estimation is based mainly on the visual observation of cadaverous phenomena (e.g. algor, livor and rigor mortis) and on alternative methods such as thanatochemistry that remain relatively imprecise. The aim of this in vitro study was to evaluate the kinetic alterations of several biochemical parameters (i.e. proteins, enzymes, substrates, electrolytes and lipids) during putrefaction of human blood. For this purpose, we performed kinetic biochemical analysis during a 264 hour period. The results showed a significant linear correlation between total and direct bilirubin, urea, uric acid, transferrin, immunoglobulin M (IgM), creatine kinase (CK), aspartate transaminase (AST), calcium and iron with the time of blood putrefaction. These parameters allowed us to develop two mathematical models that may have predictive values and become important complementary tools of traditional methods to achieve a more accurate PMI estimation. © 2015 The Royal Society of Chemistry.}, note = {cited By 12}, keywords = {}, pubstate = {published}, tppubtype = {article} } A precise estimation of the postmortem interval (PMI) is one of the most important topics in forensic pathology. However, the PMI estimation is based mainly on the visual observation of cadaverous phenomena (e.g. algor, livor and rigor mortis) and on alternative methods such as thanatochemistry that remain relatively imprecise. The aim of this in vitro study was to evaluate the kinetic alterations of several biochemical parameters (i.e. proteins, enzymes, substrates, electrolytes and lipids) during putrefaction of human blood. For this purpose, we performed kinetic biochemical analysis during a 264 hour period. The results showed a significant linear correlation between total and direct bilirubin, urea, uric acid, transferrin, immunoglobulin M (IgM), creatine kinase (CK), aspartate transaminase (AST), calcium and iron with the time of blood putrefaction. These parameters allowed us to develop two mathematical models that may have predictive values and become important complementary tools of traditional methods to achieve a more accurate PMI estimation. © 2015 The Royal Society of Chemistry. |
Mendes, R; Santos, S; Taveira, F; Dinis-Oliveira, R J; Santos, A; Magalhães, T Child Suicide in the North of Portugal Journal Article Journal of Forensic Sciences, 60 (2), pp. 471-475, 2015, (cited By 6). @article{Mendes2015471b, title = {Child Suicide in the North of Portugal}, author = {R Mendes and S Santos and F Taveira and R J Dinis-Oliveira and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84924278042&doi=10.1111%2f1556-4029.12685&partnerID=40&md5=6a871a0a72186bebf63f4d54122cfbc2}, doi = {10.1111/1556-4029.12685}, year = {2015}, date = {2015-01-01}, journal = {Journal of Forensic Sciences}, volume = {60}, number = {2}, pages = {471-475}, abstract = {Suicide in children is a rare finding and is probably motivated by acts of impulsiveness. This study aims to contribute to the characterization of child suicide in a forensic perspective in the Portuguese population. Data of forensic autopsies from 2004 to 2012 related to suicide victims under 18 years were reviewed. A total of 17 cases, with a male predominance (64.7%) and a mean age of 15.24 ± 1.348 for both genders, were registered. The leading suicide method was hanging (35.3%), and a suicide note was found in 41.2%. Psychological autopsy proved to be useful in promoting a better understanding of these incidents and their antecedents. This study also offers useful information, namely the implied risk factors, for future programs of suicide research and prevention. © 2014 American Academy of Forensic Sciences.}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } Suicide in children is a rare finding and is probably motivated by acts of impulsiveness. This study aims to contribute to the characterization of child suicide in a forensic perspective in the Portuguese population. Data of forensic autopsies from 2004 to 2012 related to suicide victims under 18 years were reviewed. A total of 17 cases, with a male predominance (64.7%) and a mean age of 15.24 ± 1.348 for both genders, were registered. The leading suicide method was hanging (35.3%), and a suicide note was found in 41.2%. Psychological autopsy proved to be useful in promoting a better understanding of these incidents and their antecedents. This study also offers useful information, namely the implied risk factors, for future programs of suicide research and prevention. © 2014 American Academy of Forensic Sciences. |
2014 |
Dinis-Oliveira, R J Licit and ilicit uses of medicines [Usos Lícito e Ilícito dos Fármacos] Journal Article 27 (6), pp. 755-766, 2014, (cited By 2). @article{Dinis-Oliveira2014755, title = {Licit and ilicit uses of medicines [Usos Lícito e Ilícito dos Fármacos]}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84920111686&partnerID=40&md5=ad15ceca68ddcdbc7aec0e9e00346389}, year = {2014}, date = {2014-01-01}, volume = {27}, number = {6}, pages = {755-766}, abstract = {Drugs of abuse are a heterogeneous group of xenobiotics or endobiotics that alter synaptic organization in the central nervous system in a transient or permanent basis, often leading to a compulsively use. What unites its members is that they confer pleasure (hedonism) to the abusers, namely by their action in the mesolimbic dopamine system. To exert its effects, different drugs of abuse will act on receptors and neurotransmitter transporters, modeling neurotransmitter release into the synaptic cleft. Besides acting on presynaptic neurons also function in neurotransmitter receptors and ion channels in postsynaptic neurons, thereby modifying the signaling pathways. In this work, the pharmacodynamic and the potential of some psychoactive substances that are typically subjected to abuse in Portugal, is reviewed. With this approach it was also possible a discussion of drugs of abuse that exhibit very different toxicological effects such as stimulants, depressants and hallucinogens. Particularly, the potential to induce dependence and addition, as well as to undergo illicit and licit uses, of central nervous system depressants, stimulants, anticholinergic antiparkinson drugs, opioids, cannabinoids and hallucinogens, is discussed. © Ordem dos Médicos 2014.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Drugs of abuse are a heterogeneous group of xenobiotics or endobiotics that alter synaptic organization in the central nervous system in a transient or permanent basis, often leading to a compulsively use. What unites its members is that they confer pleasure (hedonism) to the abusers, namely by their action in the mesolimbic dopamine system. To exert its effects, different drugs of abuse will act on receptors and neurotransmitter transporters, modeling neurotransmitter release into the synaptic cleft. Besides acting on presynaptic neurons also function in neurotransmitter receptors and ion channels in postsynaptic neurons, thereby modifying the signaling pathways. In this work, the pharmacodynamic and the potential of some psychoactive substances that are typically subjected to abuse in Portugal, is reviewed. With this approach it was also possible a discussion of drugs of abuse that exhibit very different toxicological effects such as stimulants, depressants and hallucinogens. Particularly, the potential to induce dependence and addition, as well as to undergo illicit and licit uses, of central nervous system depressants, stimulants, anticholinergic antiparkinson drugs, opioids, cannabinoids and hallucinogens, is discussed. © Ordem dos Médicos 2014. |
Dinis-Oliveira, R J Metabolomics of drugs of abuse: A more realistic view of the toxicological complexity Journal Article 6 (23), pp. 3155-3159, 2014, (cited By 20). @article{Dinis-Oliveira20143155, title = {Metabolomics of drugs of abuse: A more realistic view of the toxicological complexity}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84919783310&doi=10.4155%2fbio.14.260&partnerID=40&md5=437452c2d0a0f295a5e47062021b34ff}, doi = {10.4155/bio.14.260}, year = {2014}, date = {2014-01-01}, volume = {6}, number = {23}, pages = {3155-3159}, note = {cited By 20}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dinis-Oliveira, R J Heterogeneous and homogeneous immunoassays for drug analysis Journal Article 6 (21), pp. 2877-2896, 2014, (cited By 7). @article{Dinis-Oliveira20142877, title = {Heterogeneous and homogeneous immunoassays for drug analysis}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84918500311&doi=10.4155%2fbio.14.208&partnerID=40&md5=3466196652b70cf9d8f81e1d6010cae7}, doi = {10.4155/bio.14.208}, year = {2014}, date = {2014-01-01}, volume = {6}, number = {21}, pages = {2877-2896}, abstract = {Immunoassays are very useful techniques to perform screening and semi-quantitative analysis of hundreds of different xenobiotics. Small sample volumes are required and pretreatment is usually unnecessary (e.g., homogeneous immunoassays). Fully automated and high-throughput systems are available, which help physicians to take timely decisions. However, immunoassays do suffer from interference from both endogenous and exogenous factors that limit their application in quantitative analysis. These assays use different labels (e.g., colorimetric, fluorescent, chemiluminescent or electrochemiluminescent) and different methods for generating and measuring signals, but the basic principles are usually similar. This review outlines the practical aspects of immunoassays in bioanalysis and describes their application in clinical chemistry for xenobiotic analysis, namely medicines and drugs of abuse. © 2014 Future Science Ltd.}, note = {cited By 7}, keywords = {}, pubstate = {published}, tppubtype = {article} } Immunoassays are very useful techniques to perform screening and semi-quantitative analysis of hundreds of different xenobiotics. Small sample volumes are required and pretreatment is usually unnecessary (e.g., homogeneous immunoassays). Fully automated and high-throughput systems are available, which help physicians to take timely decisions. However, immunoassays do suffer from interference from both endogenous and exogenous factors that limit their application in quantitative analysis. These assays use different labels (e.g., colorimetric, fluorescent, chemiluminescent or electrochemiluminescent) and different methods for generating and measuring signals, but the basic principles are usually similar. This review outlines the practical aspects of immunoassays in bioanalysis and describes their application in clinical chemistry for xenobiotic analysis, namely medicines and drugs of abuse. © 2014 Future Science Ltd. |
Magalhães, T; Dinis-Oliveira, R J; Santos, A Teaching forensic medicine in the University of Porto Journal Article 25 , pp. 45-48, 2014, (cited By 5). @article{Magalhães201445, title = {Teaching forensic medicine in the University of Porto}, author = {T Magalhães and R J Dinis-Oliveira and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84900402225&doi=10.1016%2fj.jflm.2014.04.011&partnerID=40&md5=bb65c0572416a1c886a1c108739114ad}, doi = {10.1016/j.jflm.2014.04.011}, year = {2014}, date = {2014-01-01}, volume = {25}, pages = {45-48}, abstract = {The University of Porto (UP) provides education in Forensic Medicine (FM) through the 1st, 2nd and 3rd cycle of studies, post-graduation and continuing education courses. This education is related to forensic pathology, clinical forensic medicine (including forensic psychology and psychiatry), forensic chemistry and toxicology, forensic genetics and biology, and criminalistics. With this work we intent to reflect on how we are currently teaching FM in the UP, at all levels of university graduation. We will present our models, regarding the educational objectives, curricular program and teaching/learning methodologies of each cycle of studies as well as in post-graduate and continuing education courses. Historically, and besides related administratively to the Ministry of Justice, the Portuguese Medico-Legal Institutes (since 1918) and more recently the National Institute of Legal Medicine and Forensic Sciences (INMLCF) also have educational and research responsibilities. Thus, it lends space and cooperates with academic institutions and this contribution, namely regarding teaching forensic sciences in Portugal has been judged as an example for other Countries. This contribution is so important that in UP, the Department of Legal Medicine and Forensic Sciences of the Faculty of Medicine (FMUP) shares, until now, the same physical space with North Branch of the INMLCF, which represents a notorious advantage, since it makes possible the "learning by doing". © 2014 Elsevier Ltd. All rights reserved.}, note = {cited By 5}, keywords = {}, pubstate = {published}, tppubtype = {article} } The University of Porto (UP) provides education in Forensic Medicine (FM) through the 1st, 2nd and 3rd cycle of studies, post-graduation and continuing education courses. This education is related to forensic pathology, clinical forensic medicine (including forensic psychology and psychiatry), forensic chemistry and toxicology, forensic genetics and biology, and criminalistics. With this work we intent to reflect on how we are currently teaching FM in the UP, at all levels of university graduation. We will present our models, regarding the educational objectives, curricular program and teaching/learning methodologies of each cycle of studies as well as in post-graduate and continuing education courses. Historically, and besides related administratively to the Ministry of Justice, the Portuguese Medico-Legal Institutes (since 1918) and more recently the National Institute of Legal Medicine and Forensic Sciences (INMLCF) also have educational and research responsibilities. Thus, it lends space and cooperates with academic institutions and this contribution, namely regarding teaching forensic sciences in Portugal has been judged as an example for other Countries. This contribution is so important that in UP, the Department of Legal Medicine and Forensic Sciences of the Faculty of Medicine (FMUP) shares, until now, the same physical space with North Branch of the INMLCF, which represents a notorious advantage, since it makes possible the "learning by doing". © 2014 Elsevier Ltd. All rights reserved. |
Falcão, V; Jardim, P; Dinis-Oliveira, R J; Magalhães, T Forensic evaluation in alleged sibling incest against children Journal Article 23 (7), pp. 755-767, 2014, (cited By 3). @article{Falcão2014755, title = {Forensic evaluation in alleged sibling incest against children}, author = {V Falcão and P Jardim and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84918530056&doi=10.1080%2f10538712.2014.949394&partnerID=40&md5=0a649c6716290fbe6bc05cb1e1b153cd}, doi = {10.1080/10538712.2014.949394}, year = {2014}, date = {2014-01-01}, volume = {23}, number = {7}, pages = {755-767}, abstract = {Sibling incest is a serious form of intrafamilial sexual abuse with health, social, and legal relevance. A retrospective study was conducted through the analysis of forensic medical reports of the alleged sibling incest of victims under 18 years old ( n = 68) from 2004 to 2011 as well as the respective judicial outcomes. Results demonstrated that sibling's sexual abuse is associated with several circumstances that might exacerbate its severity such as vaginal, anal, and/or oral penetration. Moreover, the victim's young age, the proximity between victim and abuser, and the fact that it is committed at the victim's and /or abuser's home and by using physical violence and verbal threats justify a late detection of these cases. Copyright © Taylor & Francis Group, LLC.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sibling incest is a serious form of intrafamilial sexual abuse with health, social, and legal relevance. A retrospective study was conducted through the analysis of forensic medical reports of the alleged sibling incest of victims under 18 years old ( n = 68) from 2004 to 2011 as well as the respective judicial outcomes. Results demonstrated that sibling's sexual abuse is associated with several circumstances that might exacerbate its severity such as vaginal, anal, and/or oral penetration. Moreover, the victim's young age, the proximity between victim and abuser, and the fact that it is committed at the victim's and /or abuser's home and by using physical violence and verbal threats justify a late detection of these cases. Copyright © Taylor & Francis Group, LLC. |
Silva, A C; Santos, L; Dinis-Oliveira, R J; Magalhães, T; Santos, A Sudden Cardiac Death in Young Adult Journal Article 14 (4), pp. 379-386, 2014, (cited By 0). @article{Silva2014379, title = {Sudden Cardiac Death in Young Adult}, author = {A C Silva and L Santos and R J Dinis-Oliveira and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897358684&doi=10.1007%2fs12012-014-9255-1&partnerID=40&md5=33b8d5856968d5c2971b6204c5a530e3}, doi = {10.1007/s12012-014-9255-1}, year = {2014}, date = {2014-01-01}, volume = {14}, number = {4}, pages = {379-386}, abstract = {Cardiovascular disease represents one of the most important public health problem in the Western countries, with sudden cardiac death (SCD) being the most common cause of death in adults under 65 years of age. The objective of the present study is to evaluate the leading causes of SCD in young adults who died suddenly in Northern Portugal between 2007 and 2012. This study included 288 cases of 20- to 45-year-old adults who died suddenly of a cardiac cause and whose forensic autopsy was performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences between 2007 and 2012. Data included the cause of death, forensic autopsy findings, previous medical history and cardiovascular risk factors. The mean age of the population was 37.36 years. Coronary artery disease (CAD) was the leading cause of death, representing 55.6 % of all cases (92.5 % of men and 7.5 % of women). Females died mostly from probable primary arrhythmia. From those who died of coronary disease, 72 (25 % of total cases) had histological evidence of a fatal acute infarction. Age, previous coronary disease, hypercholesterolemia, smoking habits and alcohol consumption seem to be associated with an increased risk of SCD by CAD. A total of 55.6 % of deaths were attributed to CAD. Prevention of cardiovascular risk factors should therefore be considered to prevent atherosclerosis in young adults. © 2014, Springer Science+Business Media New York.}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cardiovascular disease represents one of the most important public health problem in the Western countries, with sudden cardiac death (SCD) being the most common cause of death in adults under 65 years of age. The objective of the present study is to evaluate the leading causes of SCD in young adults who died suddenly in Northern Portugal between 2007 and 2012. This study included 288 cases of 20- to 45-year-old adults who died suddenly of a cardiac cause and whose forensic autopsy was performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences between 2007 and 2012. Data included the cause of death, forensic autopsy findings, previous medical history and cardiovascular risk factors. The mean age of the population was 37.36 years. Coronary artery disease (CAD) was the leading cause of death, representing 55.6 % of all cases (92.5 % of men and 7.5 % of women). Females died mostly from probable primary arrhythmia. From those who died of coronary disease, 72 (25 % of total cases) had histological evidence of a fatal acute infarction. Age, previous coronary disease, hypercholesterolemia, smoking habits and alcohol consumption seem to be associated with an increased risk of SCD by CAD. A total of 55.6 % of deaths were attributed to CAD. Prevention of cardiovascular risk factors should therefore be considered to prevent atherosclerosis in young adults. © 2014, Springer Science+Business Media New York. |
Baltazar, M T; Dinis-Oliveira, R J; Bastos, M D L; Duarte, J A; Carvalho, F Lysine acetylsalicylate improves the safety of paraquat formulation in rats by increasing its elimination and preventing lung and kidney injury Journal Article 3 (4), pp. 266-277, 2014, (cited By 2). @article{Baltazar2014266, title = {Lysine acetylsalicylate improves the safety of paraquat formulation in rats by increasing its elimination and preventing lung and kidney injury}, author = {M T Baltazar and R J Dinis-Oliveira and M D L Bastos and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84902356900&doi=10.1039%2fc3tx50102g&partnerID=40&md5=f758f62054cb8885f7fbfec7101abeaf}, doi = {10.1039/c3tx50102g}, year = {2014}, date = {2014-01-01}, volume = {3}, number = {4}, pages = {266-277}, abstract = {The incorporation of lysine acetylsalicylate (LAS) in the commercial formulation of paraquat (PQ), Gramoxone®, has been shown to significantly increase the survival of intoxicated mammals while maintaining the herbicidal effect. The aim of the present study was to clarify the mechanisms involved in the protective effect of LAS in a rodent model through monitoring PQ levels and the histological and biochemical biomarkers of toxicity in male Wistar rats following intoxication with PQ formulations in the absence and presence of LAS. Gramoxone® and the formulation with LAS were administered by gavage at the doses of 125 mg kg-1 of PQ and 125 mg kg-1 of PQ + 316 mg kg-1 of LAS, respectively. The obtained results showed that LAS improves the safety of PQ formulation by increasing its elimination and preventing lung and kidney injury. LAS prevented the biochemical and histological alterations in lung induced by PQ measured at the end of 24 h and 48 h. This was evidenced by a significant reduction in lipid peroxidation, the maintenance of reduced glutathione levels and decreased levels of oxidized glutathione, as well as the normalization of the urinary biomarkers, creatinine and N-acetyl-β-glucosaminidase. LAS treatment also caused a significant reduction in PQ-induced activation of nuclear factor kappa B (NF-κB) in the lung. The results allow us to conclude that lysine acetylsalicylate improves the safety of PQ formulation in rats by increasing its elimination and preventing lung and kidney injury. This journal is © the Partner Organisations 2014.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } The incorporation of lysine acetylsalicylate (LAS) in the commercial formulation of paraquat (PQ), Gramoxone®, has been shown to significantly increase the survival of intoxicated mammals while maintaining the herbicidal effect. The aim of the present study was to clarify the mechanisms involved in the protective effect of LAS in a rodent model through monitoring PQ levels and the histological and biochemical biomarkers of toxicity in male Wistar rats following intoxication with PQ formulations in the absence and presence of LAS. Gramoxone® and the formulation with LAS were administered by gavage at the doses of 125 mg kg-1 of PQ and 125 mg kg-1 of PQ + 316 mg kg-1 of LAS, respectively. The obtained results showed that LAS improves the safety of PQ formulation by increasing its elimination and preventing lung and kidney injury. LAS prevented the biochemical and histological alterations in lung induced by PQ measured at the end of 24 h and 48 h. This was evidenced by a significant reduction in lipid peroxidation, the maintenance of reduced glutathione levels and decreased levels of oxidized glutathione, as well as the normalization of the urinary biomarkers, creatinine and N-acetyl-β-glucosaminidase. LAS treatment also caused a significant reduction in PQ-induced activation of nuclear factor kappa B (NF-κB) in the lung. The results allow us to conclude that lysine acetylsalicylate improves the safety of PQ formulation in rats by increasing its elimination and preventing lung and kidney injury. This journal is © the Partner Organisations 2014. |
Gomes, V; Jardim, P; Taveira, F; Dinis-Oliveira, R J; Magalhães, T Alleged Biological Father Incest: A Forensic Approach Journal Article 59 (1), pp. 255-259, 2014, (cited By 6). @article{Gomes2014255, title = {Alleged Biological Father Incest: A Forensic Approach}, author = {V Gomes and P Jardim and F Taveira and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84891835706&doi=10.1111%2f1556-4029.12310&partnerID=40&md5=9071801769865d3680eb969120d7ab52}, doi = {10.1111/1556-4029.12310}, year = {2014}, date = {2014-01-01}, volume = {59}, number = {1}, pages = {255-259}, abstract = {Paternal incest is one of the most serious forms of intrafamilial sexual abuse with clinical, social, and legal relevance. A retrospective study was performed, based on forensic reports and judicial decisions of alleged cases of biological paternal incest of victims under 18 years old (n = 215) from 2003 to 2008. Results highlight that in a relevant number of cases: victims were female; the abuse begun at an early age with reiteration; the alleged perpetrator presented a history of sexual crimes against children; sexual practices were physically poorly intrusive, which associated with a forensic medical evaluation performed more than 72 h after the abuse, explain partially the absence of physical injuries or other evidence-these last aspects are different from extrafamilial cases. In conclusion, observations about paternal incest are likely to exacerbate the psychosocial consequences of the abuse and may explain the difficulty and delay in detect and disclose these cases. Few cases were legally prosecuted and convicted. © 2013 American Academy of Forensic Sciences.}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } Paternal incest is one of the most serious forms of intrafamilial sexual abuse with clinical, social, and legal relevance. A retrospective study was performed, based on forensic reports and judicial decisions of alleged cases of biological paternal incest of victims under 18 years old (n = 215) from 2003 to 2008. Results highlight that in a relevant number of cases: victims were female; the abuse begun at an early age with reiteration; the alleged perpetrator presented a history of sexual crimes against children; sexual practices were physically poorly intrusive, which associated with a forensic medical evaluation performed more than 72 h after the abuse, explain partially the absence of physical injuries or other evidence-these last aspects are different from extrafamilial cases. In conclusion, observations about paternal incest are likely to exacerbate the psychosocial consequences of the abuse and may explain the difficulty and delay in detect and disclose these cases. Few cases were legally prosecuted and convicted. © 2013 American Academy of Forensic Sciences. |
Oliveira, A; Carvalho, F; Pinho, P G; Remião, F; Medeiros, R; Dinis-Oliveira, R J Quantification of morphine and its major metabolites M3G and M6G in antemortem and postmortem samples Journal Article 28 (9), pp. 1263-1270, 2014, (cited By 4). @article{Oliveira20141263, title = {Quantification of morphine and its major metabolites M3G and M6G in antemortem and postmortem samples}, author = {A Oliveira and F Carvalho and P G Pinho and F Remião and R Medeiros and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905570766&doi=10.1002%2fbmc.3158&partnerID=40&md5=c7d2a107e839c14e42e6c05fb9624550}, doi = {10.1002/bmc.3158}, year = {2014}, date = {2014-01-01}, volume = {28}, number = {9}, pages = {1263-1270}, abstract = {Morphine is one of the most effective agents for the control of significant pain, primarily metabolized to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). While M6G is a potent opioid agonist, M3G has no opioid action and seems to have a role in side-effects caused by morphine. In this study, a reversed-phase high-performance liquid chromatographic method with diode-array and electrochemical detection was developed for the simultaneous determination of morphine, M3G and M6G in antemortem and postmortem samples (plasma, whole blood, urine, liver, kidney and brain). Morphine, glucuronides and internal standard were extracted by double solid-phase extraction and the separation was carried out with a Waters Spherisorb® ODS2 reversed-phase column and potassium phosphate buffer (pH=2.2)-acetonitrile containing sodium dodecyl sulfate as the mobile phase. The method proved to be specific with good linearity for all analytes in a calibration range from 1 to 600ng/mL and proved to be accurate and have adequate precision and recovery. Limits of detection in the studied matrices were 0.4-4.5ng/mL for morphine, 2.7-6.1ng/mL for M3G and 0.8-4.4ng/mL for M6G. The proposed method can be successfully applied to quantify morphine and its metabolites in several biological samples, covering the major routes of distribution, metabolism and elimination of morphine. © 2014 John Wiley & Sons, Ltd.}, note = {cited By 4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Morphine is one of the most effective agents for the control of significant pain, primarily metabolized to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). While M6G is a potent opioid agonist, M3G has no opioid action and seems to have a role in side-effects caused by morphine. In this study, a reversed-phase high-performance liquid chromatographic method with diode-array and electrochemical detection was developed for the simultaneous determination of morphine, M3G and M6G in antemortem and postmortem samples (plasma, whole blood, urine, liver, kidney and brain). Morphine, glucuronides and internal standard were extracted by double solid-phase extraction and the separation was carried out with a Waters Spherisorb® ODS2 reversed-phase column and potassium phosphate buffer (pH=2.2)-acetonitrile containing sodium dodecyl sulfate as the mobile phase. The method proved to be specific with good linearity for all analytes in a calibration range from 1 to 600ng/mL and proved to be accurate and have adequate precision and recovery. Limits of detection in the studied matrices were 0.4-4.5ng/mL for morphine, 2.7-6.1ng/mL for M3G and 0.8-4.4ng/mL for M6G. The proposed method can be successfully applied to quantify morphine and its metabolites in several biological samples, covering the major routes of distribution, metabolism and elimination of morphine. © 2014 John Wiley & Sons, Ltd. |
Ricardo Dinis-Oliveira
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