2013 |
Sampaio-Silva, F; Magalhães, T; Carvalho, F; Dinis-Oliveira, R J; Silvestre, R Correction: Profiling of RNA degradation for estimation of post mortem interval (PLoS ONE) 8, 2 (e56507) DOI: 10.1371/journal.pone.0056507 Journal Article PLoS ONE, 8 (6), 2013, (cited By 2). @article{Sampaio-Silva2013c, title = {Correction: Profiling of RNA degradation for estimation of post mortem interval (PLoS ONE) 8, 2 (e56507) DOI: 10.1371/journal.pone.0056507}, author = {F Sampaio-Silva and T Magalhães and F Carvalho and R J Dinis-Oliveira and R Silvestre}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84896119826&doi=10.1371%2fannotation%2fcb8b37ac-cbe2-45e3-b9fe-d62e7ced4b25&partnerID=40&md5=b295907a90c9d52d20720e3c0e924f1b}, doi = {10.1371/annotation/cb8b37ac-cbe2-45e3-b9fe-d62e7ced4b25}, year = {2013}, date = {2013-01-01}, journal = {PLoS ONE}, volume = {8}, number = {6}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dinis-Oliveira, R J; Magalhães, T Children Intoxications: What is Abuse and What is Not Abuse Journal Article Trauma, Violence, and Abuse, 14 (2), pp. 113-132, 2013, (cited By 7). @article{Dinis-Oliveira2013113b, title = {Children Intoxications: What is Abuse and What is Not Abuse}, author = {R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84874421096&doi=10.1177%2f1524838012470033&partnerID=40&md5=f5f33b854d6dfa69ce64ab99cec4c6cb}, doi = {10.1177/1524838012470033}, year = {2013}, date = {2013-01-01}, journal = {Trauma, Violence, and Abuse}, volume = {14}, number = {2}, pages = {113-132}, abstract = {The curiosity and the natural tendency to explore the environment put young children at an increased risk of poisoning over older children and adults. Poisonings are a significant area of concern from 1 year of age and progressively contribute more to overall rates of morbidity and mortality until children reach adulthood. Particularly, the abuse of children by poisoning is also highly common with thousands of fatalities. A practical strategy is presented that aims to alert health, forensic, and law enforcement professionals to this problem and to demystify the preconception that it is a rare form of abuse or neglect. Compounds that are foreign to a living organism (xenobiotics) and those present within body (endobiotics), mainly involved in children intoxications and contextual examples related to exposure are also reviewed. Particular concern is given to concepts in the field of children poisoning. The described history and the clinical and toxicological evaluation are discussed, and harmonized protocols regarding correct procedures for sample collection to forensic toxicological analysis are proposed. Since children are particularly vulnerable to the toxic effects of high doses of xenobiotics and endobiotics, special consideration on the preparation of the environment that surrounds children in order minimize all possible risks will be also considered. © The Author(s) 2012.}, note = {cited By 7}, keywords = {}, pubstate = {published}, tppubtype = {article} } The curiosity and the natural tendency to explore the environment put young children at an increased risk of poisoning over older children and adults. Poisonings are a significant area of concern from 1 year of age and progressively contribute more to overall rates of morbidity and mortality until children reach adulthood. Particularly, the abuse of children by poisoning is also highly common with thousands of fatalities. A practical strategy is presented that aims to alert health, forensic, and law enforcement professionals to this problem and to demystify the preconception that it is a rare form of abuse or neglect. Compounds that are foreign to a living organism (xenobiotics) and those present within body (endobiotics), mainly involved in children intoxications and contextual examples related to exposure are also reviewed. Particular concern is given to concepts in the field of children poisoning. The described history and the clinical and toxicological evaluation are discussed, and harmonized protocols regarding correct procedures for sample collection to forensic toxicological analysis are proposed. Since children are particularly vulnerable to the toxic effects of high doses of xenobiotics and endobiotics, special consideration on the preparation of the environment that surrounds children in order minimize all possible risks will be also considered. © The Author(s) 2012. |
Barbosa, J; Faria, J; Carvalho, F; Pedro, M; Queirós, O; Moreira, R; Dinis-Oliveira, R J Hair as an alternative matrix in bioanalysis Journal Article Bioanalysis, 5 (8), pp. 895-914, 2013, (cited By 43). @article{Barbosa2013895b, title = {Hair as an alternative matrix in bioanalysis}, author = {J Barbosa and J Faria and F Carvalho and M Pedro and O Queirós and R Moreira and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876705839&doi=10.4155%2fbio.13.50&partnerID=40&md5=b9365f17618f015f9d336fc4a6c4ba11}, doi = {10.4155/bio.13.50}, year = {2013}, date = {2013-01-01}, journal = {Bioanalysis}, volume = {5}, number = {8}, pages = {895-914}, abstract = {Alternative matrices are steadily gaining recognition as biological samples for toxicological analyses. Hair presents many advantages over traditional matrices, such as urine and blood, since it provides retrospective information regarding drug exposure, can distinguish between chronic and acute or recent drug use by segmental analysis, is easy to obtain, and has considerable stability for long periods of time. For this reason, it has been employed in a wide variety of contexts, namely to evaluate workplace drug exposure, drug-facilitated sexual assault, pre-natal drug exposure, anti-doping control, pharmacological monitoring and alcohol abuse. In this article, issues concerning hair structure, collection, storage and analysis are reviewed. The mechanisms of drug incorporation into hair are briefly discussed. Analytical techniques for simultaneous drug quantification in hair are addressed. Finally, representative examples of drug quantification using hair are summarized, emphasizing its potentialities and limitations as an alternative biological matrix for toxicological analyses. © 2013 Future Science Ltd.}, note = {cited By 43}, keywords = {}, pubstate = {published}, tppubtype = {article} } Alternative matrices are steadily gaining recognition as biological samples for toxicological analyses. Hair presents many advantages over traditional matrices, such as urine and blood, since it provides retrospective information regarding drug exposure, can distinguish between chronic and acute or recent drug use by segmental analysis, is easy to obtain, and has considerable stability for long periods of time. For this reason, it has been employed in a wide variety of contexts, namely to evaluate workplace drug exposure, drug-facilitated sexual assault, pre-natal drug exposure, anti-doping control, pharmacological monitoring and alcohol abuse. In this article, issues concerning hair structure, collection, storage and analysis are reviewed. The mechanisms of drug incorporation into hair are briefly discussed. Analytical techniques for simultaneous drug quantification in hair are addressed. Finally, representative examples of drug quantification using hair are summarized, emphasizing its potentialities and limitations as an alternative biological matrix for toxicological analyses. © 2013 Future Science Ltd. |
Baltazar, M T; Dinis-Oliveira, R J; Guilhermino, L; de Bastos, Lourdes M; Duarte, J A; Carvalho, F New formulation of paraquat with lysine acetylsalicylate with low mammalian toxicity and effective herbicidal activity Journal Article Pest Management Science, 69 (4), pp. 553-558, 2013, (cited By 10). @article{Baltazar2013553b, title = {New formulation of paraquat with lysine acetylsalicylate with low mammalian toxicity and effective herbicidal activity}, author = {M T Baltazar and R J Dinis-Oliveira and L Guilhermino and M de Lourdes Bastos and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84875551483&doi=10.1002%2fps.3412&partnerID=40&md5=0df4de8812a3f55d9450df9b14354215}, doi = {10.1002/ps.3412}, year = {2013}, date = {2013-01-01}, journal = {Pest Management Science}, volume = {69}, number = {4}, pages = {553-558}, abstract = {Background: Currently, the commercial formulations of the herbicide paraquat are highly toxic to humans, and no effective antidote is available for paraquat poisoning. The aim of the present study was to develop a safe formulation, combining paraquat and the known antidote lysine acetylsalicylate. The toxicity of a mixture of Gramoxone® (20% paraquat) and lysine acetylsalicylate in adult Wistar male rats and the herbicidal efficacy against grass lawn (50% of Poa pratensis and 50% of Festuca arundinacea) were evaluated. This new formulation was administered to Wistar rats by gavage at 125 mg kg-1 of paraquat ion and lysine acetylsalicylate at 79, 158 or 316 mg kg-1 body weight, and the survival rate was observed for 30 days. Results: The survival rate of the paraquat group was only 40%, while lysine acetylsalicylate provided effective protection, with full survival observed in the groups that received 125 mg kg-1 of paraquat ion and 316 mg kg-1 of lysine acetylsalicylate. Both formulations of paraquat, either in the absence or in the presence of lysine acetylsalicylate, provided the same herbicidal activity against the tested herbal species. Conclusions: The present formulation of paraquat containing lysine acetylsalicylate, significantly decreases mammalian toxicity while maintaining effective herbicidal activity. © 2012 Society of Chemical Industry.}, note = {cited By 10}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Currently, the commercial formulations of the herbicide paraquat are highly toxic to humans, and no effective antidote is available for paraquat poisoning. The aim of the present study was to develop a safe formulation, combining paraquat and the known antidote lysine acetylsalicylate. The toxicity of a mixture of Gramoxone® (20% paraquat) and lysine acetylsalicylate in adult Wistar male rats and the herbicidal efficacy against grass lawn (50% of Poa pratensis and 50% of Festuca arundinacea) were evaluated. This new formulation was administered to Wistar rats by gavage at 125 mg kg-1 of paraquat ion and lysine acetylsalicylate at 79, 158 or 316 mg kg-1 body weight, and the survival rate was observed for 30 days. Results: The survival rate of the paraquat group was only 40%, while lysine acetylsalicylate provided effective protection, with full survival observed in the groups that received 125 mg kg-1 of paraquat ion and 316 mg kg-1 of lysine acetylsalicylate. Both formulations of paraquat, either in the absence or in the presence of lysine acetylsalicylate, provided the same herbicidal activity against the tested herbal species. Conclusions: The present formulation of paraquat containing lysine acetylsalicylate, significantly decreases mammalian toxicity while maintaining effective herbicidal activity. © 2012 Society of Chemical Industry. |
Sampaio-Silva, F; Magalhães, T; Carvalho, F; Dinis-Oliveira, R J; Silvestre, R Profiling of RNA Degradation for Estimation of Post Morterm Interval Journal Article PLoS ONE, 8 (2), 2013, (cited By 50). @article{Sampaio-Silva2013d, title = {Profiling of RNA Degradation for Estimation of Post Morterm Interval}, author = {F Sampaio-Silva and T Magalhães and F Carvalho and R J Dinis-Oliveira and R Silvestre}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84874242041&doi=10.1371%2fjournal.pone.0056507&partnerID=40&md5=7bea80f88d8d4b250b17414aaa43d314}, doi = {10.1371/journal.pone.0056507}, year = {2013}, date = {2013-01-01}, journal = {PLoS ONE}, volume = {8}, number = {2}, abstract = {An estimation of the post mortem interval (PMI) is frequently touted as the Holy Grail of forensic pathology. During the first hours after death, PMI estimation is dependent on the rate of physical observable modifications including algor, rigor and livor mortis. However, these assessment methods are still largely unreliable and inaccurate. Alternatively, RNA has been put forward as a valuable tool in forensic pathology, namely to identify body fluids, estimate the age of biological stains and to study the mechanism of death. Nevertheless, the attempts to find correlation between RNA degradation and PMI have been unsuccessful. The aim of this study was to characterize the RNA degradation in different post mortem tissues in order to develop a mathematical model that can be used as coadjuvant method for a more accurate PMI determination. For this purpose, we performed an eleven-hour kinetic analysis of total extracted RNA from murine's visceral and muscle tissues. The degradation profile of total RNA and the expression levels of several reference genes were analyzed by quantitative real-time PCR. A quantitative analysis of normalized transcript levels on the former tissues allowed the identification of four quadriceps muscle genes (Actb, Gapdh, Ppia and Srp72) that were found to significantly correlate with PMI. These results allowed us to develop a mathematical model with predictive value for estimation of the PMI (confidence interval of ±51 minutes at 95%) that can become an important complementary tool for traditional methods. © 2013 Sampaio-Silva et al.}, note = {cited By 50}, keywords = {}, pubstate = {published}, tppubtype = {article} } An estimation of the post mortem interval (PMI) is frequently touted as the Holy Grail of forensic pathology. During the first hours after death, PMI estimation is dependent on the rate of physical observable modifications including algor, rigor and livor mortis. However, these assessment methods are still largely unreliable and inaccurate. Alternatively, RNA has been put forward as a valuable tool in forensic pathology, namely to identify body fluids, estimate the age of biological stains and to study the mechanism of death. Nevertheless, the attempts to find correlation between RNA degradation and PMI have been unsuccessful. The aim of this study was to characterize the RNA degradation in different post mortem tissues in order to develop a mathematical model that can be used as coadjuvant method for a more accurate PMI determination. For this purpose, we performed an eleven-hour kinetic analysis of total extracted RNA from murine's visceral and muscle tissues. The degradation profile of total RNA and the expression levels of several reference genes were analyzed by quantitative real-time PCR. A quantitative analysis of normalized transcript levels on the former tissues allowed the identification of four quadriceps muscle genes (Actb, Gapdh, Ppia and Srp72) that were found to significantly correlate with PMI. These results allowed us to develop a mathematical model with predictive value for estimation of the PMI (confidence interval of ±51 minutes at 95%) that can become an important complementary tool for traditional methods. © 2013 Sampaio-Silva et al. |
Silva, R; Carmo, H; Vilas-Boas, V; Pinho, P G D; Dinis-Oliveira, R J; Carvalho, F; Silva, I; Correia-de-Sá, P; Bastos, M D L; Remião, F Doxorubicin decreases paraquat accumulation and toxicity in Caco-2 cells Journal Article Toxicology Letters, 217 (1), pp. 34-41, 2013, (cited By 12). @article{Silva201334b, title = {Doxorubicin decreases paraquat accumulation and toxicity in Caco-2 cells}, author = {R Silva and H Carmo and V Vilas-Boas and P G D Pinho and R J Dinis-Oliveira and F Carvalho and I Silva and P Correia-de-Sá and M D L Bastos and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84872136547&doi=10.1016%2fj.toxlet.2012.11.028&partnerID=40&md5=db04ef5600339dc0cb06057f9f21d496}, doi = {10.1016/j.toxlet.2012.11.028}, year = {2013}, date = {2013-01-01}, journal = {Toxicology Letters}, volume = {217}, number = {1}, pages = {34-41}, abstract = {P-glycoprotein (P-gp) is an efflux pump belonging to the ATP-binding cassette transporter superfamily expressed in several organs. Considering its potential protective effects, the induction of de novo synthesis of P-gp could be used therapeutically in the treatment of intoxications by its substrates. The herbicide paraquat (PQ) is a P-gp substrate responsible for thousands of fatal intoxications worldwide that still lacks an effective antidote. The aim of the present work was to evaluate the effectiveness of such an antidote by testing whether doxorubicin (DOX), a known P-gp inducer, could efficiently protect Caco-2 cells against PQ cytotoxicity, 6h after the incubation with the herbicide, reflecting a real-life intoxication scenario. Cytotoxicity was evaluated by the MTT assay and PQ intracellular concentrations were measured by gas chromatography-ion trap-mass spectrometry (GC-IT-MS). Also, the DOX modulatory effect on choline uptake transport system was assessed by measuring the uptake of [3H]-choline. The results show that DOX exerts protective effects against PQ cytotoxicity, preventing the intracellular accumulation of the herbicide. These protective effects were not completely prevented by the incubation with the UIC2 antibody, a specific P-gp inhibitor, suggesting the involvement of alternative protection mechanisms. In fact, DOX also efficiently inhibited the choline transport system that influences PQ cellular uptake. In conclusion, in this cellular model, DOX effectively protects against PQ toxicity by inducing P-gp and through the interaction with the choline transporter, suggesting that compounds presenting this double feature of promoting the efflux and limiting the uptake of PQ could be used as effective antidotes to treat intoxications. © 2012 Elsevier Ireland Ltd.}, note = {cited By 12}, keywords = {}, pubstate = {published}, tppubtype = {article} } P-glycoprotein (P-gp) is an efflux pump belonging to the ATP-binding cassette transporter superfamily expressed in several organs. Considering its potential protective effects, the induction of de novo synthesis of P-gp could be used therapeutically in the treatment of intoxications by its substrates. The herbicide paraquat (PQ) is a P-gp substrate responsible for thousands of fatal intoxications worldwide that still lacks an effective antidote. The aim of the present work was to evaluate the effectiveness of such an antidote by testing whether doxorubicin (DOX), a known P-gp inducer, could efficiently protect Caco-2 cells against PQ cytotoxicity, 6h after the incubation with the herbicide, reflecting a real-life intoxication scenario. Cytotoxicity was evaluated by the MTT assay and PQ intracellular concentrations were measured by gas chromatography-ion trap-mass spectrometry (GC-IT-MS). Also, the DOX modulatory effect on choline uptake transport system was assessed by measuring the uptake of [3H]-choline. The results show that DOX exerts protective effects against PQ cytotoxicity, preventing the intracellular accumulation of the herbicide. These protective effects were not completely prevented by the incubation with the UIC2 antibody, a specific P-gp inhibitor, suggesting the involvement of alternative protection mechanisms. In fact, DOX also efficiently inhibited the choline transport system that influences PQ cellular uptake. In conclusion, in this cellular model, DOX effectively protects against PQ toxicity by inducing P-gp and through the interaction with the choline transporter, suggesting that compounds presenting this double feature of promoting the efflux and limiting the uptake of PQ could be used as effective antidotes to treat intoxications. © 2012 Elsevier Ireland Ltd. |
Baltazar, T; Dinis-Oliveira, R J; Duarte, J A; Bastos, De Lourdes M; Carvalho, F Paraquat research: Do recent advances in limiting its toxicity make its use safer? Journal Article British Journal of Pharmacology, 168 (1), pp. 44-45, 2013, (cited By 22). @article{Baltazar201344b, title = {Paraquat research: Do recent advances in limiting its toxicity make its use safer?}, author = {T Baltazar and R J Dinis-Oliveira and J A Duarte and M De Lourdes Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84872031404&doi=10.1111%2fj.1476-5381.2012.02017.x&partnerID=40&md5=280542794da504bc08fa52d41a4d7a37}, doi = {10.1111/j.1476-5381.2012.02017.x}, year = {2013}, date = {2013-01-01}, journal = {British Journal of Pharmacology}, volume = {168}, number = {1}, pages = {44-45}, abstract = {The use of the herbicide paraquat (1,1′-dimethyl-4,4′- bipyridylium dichloride; PQ) has been fiercely challenged due to its severe acute toxicity, putative neurotoxicity after long-term exposure and lack of antidotes. Breakthrough research on PQ is therefore required for an effective risk control and to allow a safer use of PQ in the future. The silencing or inhibition of quinone oxidoreductase 2, a NAD(P)H-independent flavoenzyme, was shown to significantly attenuate PQ toxicity in vitro, in primary pneumocytes and astroglial U373 cells, and to strongly antagonize PQ-induced systemic toxicity and animal mortality. The novel results reported in this issue of BJP, added to recent findings using sodium salicylate and lysine acetylsalicylate, in which full survival of PQ-intoxicated rats was also achieved, open the door for new preventative and therapeutic strategies that may lead to safer use of this effective pesticide. © 2012 The British Pharmacological Society.}, note = {cited By 22}, keywords = {}, pubstate = {published}, tppubtype = {article} } The use of the herbicide paraquat (1,1′-dimethyl-4,4′- bipyridylium dichloride; PQ) has been fiercely challenged due to its severe acute toxicity, putative neurotoxicity after long-term exposure and lack of antidotes. Breakthrough research on PQ is therefore required for an effective risk control and to allow a safer use of PQ in the future. The silencing or inhibition of quinone oxidoreductase 2, a NAD(P)H-independent flavoenzyme, was shown to significantly attenuate PQ toxicity in vitro, in primary pneumocytes and astroglial U373 cells, and to strongly antagonize PQ-induced systemic toxicity and animal mortality. The novel results reported in this issue of BJP, added to recent findings using sodium salicylate and lysine acetylsalicylate, in which full survival of PQ-intoxicated rats was also achieved, open the door for new preventative and therapeutic strategies that may lead to safer use of this effective pesticide. © 2012 The British Pharmacological Society. |
2012 |
Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Proença, J B; Santos, A; Magalhães, T Clinical and forensic signs related to cocaine abuse Journal Article 5 (1), pp. 64-83, 2012, (cited By 20). @article{Dinis-Oliveira201264, title = {Clinical and forensic signs related to cocaine abuse}, author = {R J Dinis-Oliveira and F Carvalho and J A Duarte and J B Proença and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84860286519&doi=10.2174%2f1874473711205010064&partnerID=40&md5=906cc1a2aa1590223bc371b16a21f838}, doi = {10.2174/1874473711205010064}, year = {2012}, date = {2012-01-01}, volume = {5}, number = {1}, pages = {64-83}, abstract = {Good laboratory practice in toxicological analysis requires pre-analytical steps for collection of detailed information related to the suspected poisoning episodes, including biological and non-biological circumstantial evidences, which should be carefully scrutinized. This procedure provides great help to unveil the suspected cause of poisoning, to select the appropriate and correct samples to be analyzed and can facilitate the decision about the analytical techniques to perform. This implies a good knowledge of the signs related to acute and chronic intoxications by drugs of abuse. In this manuscript we highlight and discuss clinical and forensic imaging related to cocaine abuse, namely the midline destructive lesion, dental health, pseudoscleradermatous triad and crack hands, necrosis and gangrene of extremities and several other skin manifestations, reticular purpura, intracerebral and peripheral hemorrhages, angioneurotic edema, rhabdomyolysis, and crack lung. For this purpose, the state of the art on this topic is discussed, using clinical and forensic cases from our professional database in complement to images and mechanistic data from literature. © 2012 Bentham Science Publishers.}, note = {cited By 20}, keywords = {}, pubstate = {published}, tppubtype = {article} } Good laboratory practice in toxicological analysis requires pre-analytical steps for collection of detailed information related to the suspected poisoning episodes, including biological and non-biological circumstantial evidences, which should be carefully scrutinized. This procedure provides great help to unveil the suspected cause of poisoning, to select the appropriate and correct samples to be analyzed and can facilitate the decision about the analytical techniques to perform. This implies a good knowledge of the signs related to acute and chronic intoxications by drugs of abuse. In this manuscript we highlight and discuss clinical and forensic imaging related to cocaine abuse, namely the midline destructive lesion, dental health, pseudoscleradermatous triad and crack hands, necrosis and gangrene of extremities and several other skin manifestations, reticular purpura, intracerebral and peripheral hemorrhages, angioneurotic edema, rhabdomyolysis, and crack lung. For this purpose, the state of the art on this topic is discussed, using clinical and forensic cases from our professional database in complement to images and mechanistic data from literature. © 2012 Bentham Science Publishers. |
Dinis-Oliveira, R J; Santos, A; Magalhães, T "Foam Cone" exuding from the mouth and nostrils following heroin overdose Journal Article 22 (2), pp. 159-160, 2012, (cited By 15). @article{Dinis-Oliveira2012159, title = {"Foam Cone" exuding from the mouth and nostrils following heroin overdose}, author = {R J Dinis-Oliveira and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84855876624&doi=10.3109%2f15376516.2011.610388&partnerID=40&md5=26eb2e93774a1e17d9d4c631e03bf4a6}, doi = {10.3109/15376516.2011.610388}, year = {2012}, date = {2012-01-01}, volume = {22}, number = {2}, pages = {159-160}, abstract = {A "foam cone" exuding the mouth and nostrils is a recognized consequence of anoxia following pulmonary edema. In this report, we illustrate and explain this phenomenon in victims of heroin overdose. © 2012 Informa Healthcare USA, Inc.}, note = {cited By 15}, keywords = {}, pubstate = {published}, tppubtype = {article} } A "foam cone" exuding the mouth and nostrils is a recognized consequence of anoxia following pulmonary edema. In this report, we illustrate and explain this phenomenon in victims of heroin overdose. © 2012 Informa Healthcare USA, Inc. |
Ribeiro, E; Magalhães, T; Dinis-Oliveira, R J 25 (2), pp. 111-117, 2012, (cited By 3). @article{Ribeiro2012111, title = {Mephedrone, the new designer drug of abuse: Pharmacokinetics, pharmacodynamics and clinical and forensic issues [Mefedrona, a nova droga de abuso: Farmacocinética, farmacodinâmica e implicações clínicas e forenses]}, author = {E Ribeiro and T Magalhães and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84865967149&partnerID=40&md5=14a73d249b2081c10c9c12cacb612735}, year = {2012}, date = {2012-01-01}, volume = {25}, number = {2}, pages = {111-117}, abstract = {Mephedrone is a semisynthetic derivative of cathinone used as a drug of abuse. Similar to amphetamine, both in chemical structure and associated signs and symptoms, has gained popularity since 2007 and it is currently the sixth most abused drug in United Kingdom. It can be easily purchased by the internet or smart shops where it is advertised as a fertilizer for plants or bath salts, although such efficacy was never proved. This article aims to review the state-of-the-art literature of mephedrone, particularly its chemical structure, forms of presentation, pharmacokinetics, pharmacodynamics, acute intoxications, diagnosis and therapy of intoxications. Mephedrone is mainly sought for the following symptoms: euphoria, social disinhibition, empathy, and increased libido. However, its use is associated with several adverse effects on cardiovascular, gastrointestinal, neurological, psychiatric and genitourinary systems, among others. There are also reported cases of consumers who have developed tolerance and dependence after a regular abuse of mephedrone. Several deaths in the United Kingdom have been confirmed as being directly related to the consumption of mephedrone. Currently this drug is legally controlled in many countries, but little is known about its pharmacokinetics and pharmacodynamics. Most data comes only from users and health professional's reports and internet surveys. Recently, the Portuguese Law 13/2012, 26 of March, included mephedrone in the list of controlled substances, and therefore it is important to better understand this xenobiotic. © Ordem dos médicos 2012.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mephedrone is a semisynthetic derivative of cathinone used as a drug of abuse. Similar to amphetamine, both in chemical structure and associated signs and symptoms, has gained popularity since 2007 and it is currently the sixth most abused drug in United Kingdom. It can be easily purchased by the internet or smart shops where it is advertised as a fertilizer for plants or bath salts, although such efficacy was never proved. This article aims to review the state-of-the-art literature of mephedrone, particularly its chemical structure, forms of presentation, pharmacokinetics, pharmacodynamics, acute intoxications, diagnosis and therapy of intoxications. Mephedrone is mainly sought for the following symptoms: euphoria, social disinhibition, empathy, and increased libido. However, its use is associated with several adverse effects on cardiovascular, gastrointestinal, neurological, psychiatric and genitourinary systems, among others. There are also reported cases of consumers who have developed tolerance and dependence after a regular abuse of mephedrone. Several deaths in the United Kingdom have been confirmed as being directly related to the consumption of mephedrone. Currently this drug is legally controlled in many countries, but little is known about its pharmacokinetics and pharmacodynamics. Most data comes only from users and health professional's reports and internet surveys. Recently, the Portuguese Law 13/2012, 26 of March, included mephedrone in the list of controlled substances, and therefore it is important to better understand this xenobiotic. © Ordem dos médicos 2012. |
Moreira, P N; de Pinho, P G; Baltazar, M T; Bastos, M L; Carvalho, F; Dinis-Oliveira, R J Quantification of paraquat in postmortem samples by gas chromatography-ion trap mass spectrometry and review of the literature Journal Article 26 (3), pp. 338-349, 2012, (cited By 17). @article{Moreira2012338, title = {Quantification of paraquat in postmortem samples by gas chromatography-ion trap mass spectrometry and review of the literature}, author = {P N Moreira and P G de Pinho and M T Baltazar and M L Bastos and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84856574478&doi=10.1002%2fbmc.1663&partnerID=40&md5=1ecd089494f5d70ae9baf4ba6974ec5b}, doi = {10.1002/bmc.1663}, year = {2012}, date = {2012-01-01}, volume = {26}, number = {3}, pages = {338-349}, abstract = {Paraquat (PQ) is an herbicide implicated in numerous fatalities, mainly caused by voluntary ingestion. Several methods have been used to quantify PQ in plasma and urine samples of intoxicated humans as a predictor of clinical outcome. There is no validated method for the analysis of PQ in postmortem samples. Therefore, the aim of this study was to develop an analytical method, using gas chromatography-ion trap mass spectrometry (GC-IT/MS) after solid-phase extraction, to quantify PQ in postmortem samples, namely in whole blood, urine, liver, lung and kidney, to cover the routes of distribution, accumulation and elimination of PQ. The method proved to be selective as there were no interferences of endogenous compounds with the same retention time as PQ and ethyl paraquat (internal standard). The regression analysis for PQ was linear in the range 0-10μg/mL. The detection limits ranged from 0.0076μg/mL for urine to 0.047μg/mL for whole blood, and the recoveries were suitable for forensic analysis. The proposed GC-IT/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of PQ in postmortem samples. The proof of applicability was performed in two fatal PQ intoxications. A review of the analytical methods for the determination of quaternary ammonium herbicides is also provided for a better understanding of the presently available techniques. © 2011 John Wiley & Sons, Ltd.}, note = {cited By 17}, keywords = {}, pubstate = {published}, tppubtype = {article} } Paraquat (PQ) is an herbicide implicated in numerous fatalities, mainly caused by voluntary ingestion. Several methods have been used to quantify PQ in plasma and urine samples of intoxicated humans as a predictor of clinical outcome. There is no validated method for the analysis of PQ in postmortem samples. Therefore, the aim of this study was to develop an analytical method, using gas chromatography-ion trap mass spectrometry (GC-IT/MS) after solid-phase extraction, to quantify PQ in postmortem samples, namely in whole blood, urine, liver, lung and kidney, to cover the routes of distribution, accumulation and elimination of PQ. The method proved to be selective as there were no interferences of endogenous compounds with the same retention time as PQ and ethyl paraquat (internal standard). The regression analysis for PQ was linear in the range 0-10μg/mL. The detection limits ranged from 0.0076μg/mL for urine to 0.047μg/mL for whole blood, and the recoveries were suitable for forensic analysis. The proposed GC-IT/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of PQ in postmortem samples. The proof of applicability was performed in two fatal PQ intoxications. A review of the analytical methods for the determination of quaternary ammonium herbicides is also provided for a better understanding of the presently available techniques. © 2011 John Wiley & Sons, Ltd. |
Gouveia, C A; Oliveira, A; Pinho, S; Vasconcelos, C; Carvalho, F; Moreira, R F; Dinis-Oliveira, R J Simultaneous quantification of morphine and cocaine in hair samples from drug addicts by GC-EI/MS Journal Article 26 (8), pp. 1041-1047, 2012, (cited By 14). @article{Gouveia20121041, title = {Simultaneous quantification of morphine and cocaine in hair samples from drug addicts by GC-EI/MS}, author = {C A Gouveia and A Oliveira and S Pinho and C Vasconcelos and F Carvalho and R F Moreira and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864003851&doi=10.1002%2fbmc.2775&partnerID=40&md5=a7e17b0e5b3a3b29e1cc8c2bd436c887}, doi = {10.1002/bmc.2775}, year = {2012}, date = {2012-01-01}, volume = {26}, number = {8}, pages = {1041-1047}, abstract = {The development of analytical techniques that enable the use of hair as an alternative matrix for the analysis of drugs of abuse is useful for confirming the exposure in a larger time window (weeks to months, depending on the length of the hair shaft). In the present study a methodology aimed at the simultaneous quantification of cocaine and morphine in human hair was developed and validated. After decontamination, hair samples (20mg) were incubated with a mixture of methanol/hydrochloric acid (2:1) at 65°C overnight (~16h) in order to extract the drugs of the matrix. Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. After derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide, blank, standards and samples were analyzed by gas chromatography/electron impact-mass spectrometry (GC-EI/MS). The method proved to be selective, as there were no interferences of endogenous compounds with the same retention time as cocaine, morphine and ethylmorphine (internal standard). The regression analysis for both analytes showed linearity in the range 0.25-10.00ng/mg with correlation coefficients ranging from 0.9989 to 0.9991. The coefficients of variation oscillated between 0.83 and 14.60%. The limits of detection were 0.01 and 0.02ng/mg, and the limits of quantification were 0.03 and 0.06ng/mg for cocaine and morphine, respectively. The proposed GC-EI/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of cocaine and morphine in hair samples. The proof of applicability was performed in hair samples obtained from drug addicts enrolled in a Regional Detoxification Treatment Center. The importance of hair samples is highlighted, since positives results were obtained when urine immunoassay analyses were negative. © 2012 John Wiley & Sons, Ltd.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } The development of analytical techniques that enable the use of hair as an alternative matrix for the analysis of drugs of abuse is useful for confirming the exposure in a larger time window (weeks to months, depending on the length of the hair shaft). In the present study a methodology aimed at the simultaneous quantification of cocaine and morphine in human hair was developed and validated. After decontamination, hair samples (20mg) were incubated with a mixture of methanol/hydrochloric acid (2:1) at 65°C overnight (~16h) in order to extract the drugs of the matrix. Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. After derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide, blank, standards and samples were analyzed by gas chromatography/electron impact-mass spectrometry (GC-EI/MS). The method proved to be selective, as there were no interferences of endogenous compounds with the same retention time as cocaine, morphine and ethylmorphine (internal standard). The regression analysis for both analytes showed linearity in the range 0.25-10.00ng/mg with correlation coefficients ranging from 0.9989 to 0.9991. The coefficients of variation oscillated between 0.83 and 14.60%. The limits of detection were 0.01 and 0.02ng/mg, and the limits of quantification were 0.03 and 0.06ng/mg for cocaine and morphine, respectively. The proposed GC-EI/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of cocaine and morphine in hair samples. The proof of applicability was performed in hair samples obtained from drug addicts enrolled in a Regional Detoxification Treatment Center. The importance of hair samples is highlighted, since positives results were obtained when urine immunoassay analyses were negative. © 2012 John Wiley & Sons, Ltd. |
Dinis-Oliveira, R J; Carvalho, F; Moreira, R; Duarte, J A; Proença, J B; Santos, A; Magalhães, T Clinical and forensic signs related to opioids abuse Journal Article 5 (4), pp. 273-290, 2012, (cited By 23). @article{Dinis-Oliveira2012273, title = {Clinical and forensic signs related to opioids abuse}, author = {R J Dinis-Oliveira and F Carvalho and R Moreira and J A Duarte and J B Proença and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84873154598&partnerID=40&md5=adcfe478dc61e61f54315551d5e05fe1}, year = {2012}, date = {2012-01-01}, volume = {5}, number = {4}, pages = {273-290}, abstract = {For a good performance in Clinical and Forensic Toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. This manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. Particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administration, candidiasis, wounds associated with anthrax or clostridium contaminated heroin, desomorphine related lesions and characteristic non-biological evidences are some commonly reported findings in opioids abuse, which will be discussed. For this purpose, clinical and forensic cases from our database (National Institute of Legal Medicine and Forensic Sciences, North Branch, Portugal), in addition to literature data, are reviewed. © 2012 Bentham Science Publishers.}, note = {cited By 23}, keywords = {}, pubstate = {published}, tppubtype = {article} } For a good performance in Clinical and Forensic Toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. This manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. Particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administration, candidiasis, wounds associated with anthrax or clostridium contaminated heroin, desomorphine related lesions and characteristic non-biological evidences are some commonly reported findings in opioids abuse, which will be discussed. For this purpose, clinical and forensic cases from our database (National Institute of Legal Medicine and Forensic Sciences, North Branch, Portugal), in addition to literature data, are reviewed. © 2012 Bentham Science Publishers. |
Dinis-Oliveira, R J; Carvalho, F; Moreira, R; Duarte, J A; Proença, J B; Santos, A; Magalhães, T Clinical and forensic signs related to opioids abuse Journal Article Current Drug Abuse Reviews, 5 (4), pp. 273-290, 2012, (cited By 28). @article{Dinis-Oliveira2012273b, title = {Clinical and forensic signs related to opioids abuse}, author = {R J Dinis-Oliveira and F Carvalho and R Moreira and J A Duarte and J B Proença and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84873154598&partnerID=40&md5=adcfe478dc61e61f54315551d5e05fe1}, year = {2012}, date = {2012-01-01}, journal = {Current Drug Abuse Reviews}, volume = {5}, number = {4}, pages = {273-290}, abstract = {For a good performance in Clinical and Forensic Toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. This manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. Particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administration, candidiasis, wounds associated with anthrax or clostridium contaminated heroin, desomorphine related lesions and characteristic non-biological evidences are some commonly reported findings in opioids abuse, which will be discussed. For this purpose, clinical and forensic cases from our database (National Institute of Legal Medicine and Forensic Sciences, North Branch, Portugal), in addition to literature data, are reviewed. © 2012 Bentham Science Publishers.}, note = {cited By 28}, keywords = {}, pubstate = {published}, tppubtype = {article} } For a good performance in Clinical and Forensic Toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. This manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. Particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administration, candidiasis, wounds associated with anthrax or clostridium contaminated heroin, desomorphine related lesions and characteristic non-biological evidences are some commonly reported findings in opioids abuse, which will be discussed. For this purpose, clinical and forensic cases from our database (National Institute of Legal Medicine and Forensic Sciences, North Branch, Portugal), in addition to literature data, are reviewed. © 2012 Bentham Science Publishers. |
Gouveia, C A; Oliveira, A; Pinho, S; Vasconcelos, C; Carvalho, F; Moreira, R F; Dinis-Oliveira, R J Simultaneous quantification of morphine and cocaine in hair samples from drug addicts by GC-EI/MS Journal Article Biomedical Chromatography, 26 (8), pp. 1041-1047, 2012, (cited By 16). @article{Gouveia20121041b, title = {Simultaneous quantification of morphine and cocaine in hair samples from drug addicts by GC-EI/MS}, author = {C A Gouveia and A Oliveira and S Pinho and C Vasconcelos and F Carvalho and R F Moreira and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864003851&doi=10.1002%2fbmc.2775&partnerID=40&md5=a7e17b0e5b3a3b29e1cc8c2bd436c887}, doi = {10.1002/bmc.2775}, year = {2012}, date = {2012-01-01}, journal = {Biomedical Chromatography}, volume = {26}, number = {8}, pages = {1041-1047}, abstract = {The development of analytical techniques that enable the use of hair as an alternative matrix for the analysis of drugs of abuse is useful for confirming the exposure in a larger time window (weeks to months, depending on the length of the hair shaft). In the present study a methodology aimed at the simultaneous quantification of cocaine and morphine in human hair was developed and validated. After decontamination, hair samples (20mg) were incubated with a mixture of methanol/hydrochloric acid (2:1) at 65°C overnight (~16h) in order to extract the drugs of the matrix. Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. After derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide, blank, standards and samples were analyzed by gas chromatography/electron impact-mass spectrometry (GC-EI/MS). The method proved to be selective, as there were no interferences of endogenous compounds with the same retention time as cocaine, morphine and ethylmorphine (internal standard). The regression analysis for both analytes showed linearity in the range 0.25-10.00ng/mg with correlation coefficients ranging from 0.9989 to 0.9991. The coefficients of variation oscillated between 0.83 and 14.60%. The limits of detection were 0.01 and 0.02ng/mg, and the limits of quantification were 0.03 and 0.06ng/mg for cocaine and morphine, respectively. The proposed GC-EI/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of cocaine and morphine in hair samples. The proof of applicability was performed in hair samples obtained from drug addicts enrolled in a Regional Detoxification Treatment Center. The importance of hair samples is highlighted, since positives results were obtained when urine immunoassay analyses were negative. © 2012 John Wiley & Sons, Ltd.}, note = {cited By 16}, keywords = {}, pubstate = {published}, tppubtype = {article} } The development of analytical techniques that enable the use of hair as an alternative matrix for the analysis of drugs of abuse is useful for confirming the exposure in a larger time window (weeks to months, depending on the length of the hair shaft). In the present study a methodology aimed at the simultaneous quantification of cocaine and morphine in human hair was developed and validated. After decontamination, hair samples (20mg) were incubated with a mixture of methanol/hydrochloric acid (2:1) at 65°C overnight (~16h) in order to extract the drugs of the matrix. Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. After derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide, blank, standards and samples were analyzed by gas chromatography/electron impact-mass spectrometry (GC-EI/MS). The method proved to be selective, as there were no interferences of endogenous compounds with the same retention time as cocaine, morphine and ethylmorphine (internal standard). The regression analysis for both analytes showed linearity in the range 0.25-10.00ng/mg with correlation coefficients ranging from 0.9989 to 0.9991. The coefficients of variation oscillated between 0.83 and 14.60%. The limits of detection were 0.01 and 0.02ng/mg, and the limits of quantification were 0.03 and 0.06ng/mg for cocaine and morphine, respectively. The proposed GC-EI/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of cocaine and morphine in hair samples. The proof of applicability was performed in hair samples obtained from drug addicts enrolled in a Regional Detoxification Treatment Center. The importance of hair samples is highlighted, since positives results were obtained when urine immunoassay analyses were negative. © 2012 John Wiley & Sons, Ltd. |
Ribeiro, E; Magalhães, T; Dinis-Oliveira, R J Acta Medica Portuguesa, 25 (2), pp. 111-117, 2012, (cited By 4). @article{Ribeiro2012111b, title = {Mephedrone, the new designer drug of abuse: Pharmacokinetics, pharmacodynamics and clinical and forensic issues [Mefedrona, a nova droga de abuso: Farmacocinética, farmacodinâmica e implicações clínicas e forenses]}, author = {E Ribeiro and T Magalhães and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84865967149&partnerID=40&md5=14a73d249b2081c10c9c12cacb612735}, year = {2012}, date = {2012-01-01}, journal = {Acta Medica Portuguesa}, volume = {25}, number = {2}, pages = {111-117}, abstract = {Mephedrone is a semisynthetic derivative of cathinone used as a drug of abuse. Similar to amphetamine, both in chemical structure and associated signs and symptoms, has gained popularity since 2007 and it is currently the sixth most abused drug in United Kingdom. It can be easily purchased by the internet or smart shops where it is advertised as a fertilizer for plants or bath salts, although such efficacy was never proved. This article aims to review the state-of-the-art literature of mephedrone, particularly its chemical structure, forms of presentation, pharmacokinetics, pharmacodynamics, acute intoxications, diagnosis and therapy of intoxications. Mephedrone is mainly sought for the following symptoms: euphoria, social disinhibition, empathy, and increased libido. However, its use is associated with several adverse effects on cardiovascular, gastrointestinal, neurological, psychiatric and genitourinary systems, among others. There are also reported cases of consumers who have developed tolerance and dependence after a regular abuse of mephedrone. Several deaths in the United Kingdom have been confirmed as being directly related to the consumption of mephedrone. Currently this drug is legally controlled in many countries, but little is known about its pharmacokinetics and pharmacodynamics. Most data comes only from users and health professional's reports and internet surveys. Recently, the Portuguese Law 13/2012, 26 of March, included mephedrone in the list of controlled substances, and therefore it is important to better understand this xenobiotic. © Ordem dos médicos 2012.}, note = {cited By 4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mephedrone is a semisynthetic derivative of cathinone used as a drug of abuse. Similar to amphetamine, both in chemical structure and associated signs and symptoms, has gained popularity since 2007 and it is currently the sixth most abused drug in United Kingdom. It can be easily purchased by the internet or smart shops where it is advertised as a fertilizer for plants or bath salts, although such efficacy was never proved. This article aims to review the state-of-the-art literature of mephedrone, particularly its chemical structure, forms of presentation, pharmacokinetics, pharmacodynamics, acute intoxications, diagnosis and therapy of intoxications. Mephedrone is mainly sought for the following symptoms: euphoria, social disinhibition, empathy, and increased libido. However, its use is associated with several adverse effects on cardiovascular, gastrointestinal, neurological, psychiatric and genitourinary systems, among others. There are also reported cases of consumers who have developed tolerance and dependence after a regular abuse of mephedrone. Several deaths in the United Kingdom have been confirmed as being directly related to the consumption of mephedrone. Currently this drug is legally controlled in many countries, but little is known about its pharmacokinetics and pharmacodynamics. Most data comes only from users and health professional's reports and internet surveys. Recently, the Portuguese Law 13/2012, 26 of March, included mephedrone in the list of controlled substances, and therefore it is important to better understand this xenobiotic. © Ordem dos médicos 2012. |
Moreira, P N; de Pinho, P G; Baltazar, M T; Bastos, M L; Carvalho, F; Dinis-Oliveira, R J Quantification of paraquat in postmortem samples by gas chromatography-ion trap mass spectrometry and review of the literature Journal Article Biomedical Chromatography, 26 (3), pp. 338-349, 2012, (cited By 21). @article{Moreira2012338b, title = {Quantification of paraquat in postmortem samples by gas chromatography-ion trap mass spectrometry and review of the literature}, author = {P N Moreira and P G de Pinho and M T Baltazar and M L Bastos and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84856574478&doi=10.1002%2fbmc.1663&partnerID=40&md5=1ecd089494f5d70ae9baf4ba6974ec5b}, doi = {10.1002/bmc.1663}, year = {2012}, date = {2012-01-01}, journal = {Biomedical Chromatography}, volume = {26}, number = {3}, pages = {338-349}, abstract = {Paraquat (PQ) is an herbicide implicated in numerous fatalities, mainly caused by voluntary ingestion. Several methods have been used to quantify PQ in plasma and urine samples of intoxicated humans as a predictor of clinical outcome. There is no validated method for the analysis of PQ in postmortem samples. Therefore, the aim of this study was to develop an analytical method, using gas chromatography-ion trap mass spectrometry (GC-IT/MS) after solid-phase extraction, to quantify PQ in postmortem samples, namely in whole blood, urine, liver, lung and kidney, to cover the routes of distribution, accumulation and elimination of PQ. The method proved to be selective as there were no interferences of endogenous compounds with the same retention time as PQ and ethyl paraquat (internal standard). The regression analysis for PQ was linear in the range 0-10μg/mL. The detection limits ranged from 0.0076μg/mL for urine to 0.047μg/mL for whole blood, and the recoveries were suitable for forensic analysis. The proposed GC-IT/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of PQ in postmortem samples. The proof of applicability was performed in two fatal PQ intoxications. A review of the analytical methods for the determination of quaternary ammonium herbicides is also provided for a better understanding of the presently available techniques. © 2011 John Wiley & Sons, Ltd.}, note = {cited By 21}, keywords = {}, pubstate = {published}, tppubtype = {article} } Paraquat (PQ) is an herbicide implicated in numerous fatalities, mainly caused by voluntary ingestion. Several methods have been used to quantify PQ in plasma and urine samples of intoxicated humans as a predictor of clinical outcome. There is no validated method for the analysis of PQ in postmortem samples. Therefore, the aim of this study was to develop an analytical method, using gas chromatography-ion trap mass spectrometry (GC-IT/MS) after solid-phase extraction, to quantify PQ in postmortem samples, namely in whole blood, urine, liver, lung and kidney, to cover the routes of distribution, accumulation and elimination of PQ. The method proved to be selective as there were no interferences of endogenous compounds with the same retention time as PQ and ethyl paraquat (internal standard). The regression analysis for PQ was linear in the range 0-10μg/mL. The detection limits ranged from 0.0076μg/mL for urine to 0.047μg/mL for whole blood, and the recoveries were suitable for forensic analysis. The proposed GC-IT/MS method provided an accurate and simple assay with adequate precision and recovery for the quantification of PQ in postmortem samples. The proof of applicability was performed in two fatal PQ intoxications. A review of the analytical methods for the determination of quaternary ammonium herbicides is also provided for a better understanding of the presently available techniques. © 2011 John Wiley & Sons, Ltd. |
Dinis-Oliveira, R J; Santos, A; Magalhães, T "Foam Cone" exuding from the mouth and nostrils following heroin overdose Journal Article Toxicology Mechanisms and Methods, 22 (2), pp. 159-160, 2012, (cited By 17). @article{Dinis-Oliveira2012159b, title = {"Foam Cone" exuding from the mouth and nostrils following heroin overdose}, author = {R J Dinis-Oliveira and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84855876624&doi=10.3109%2f15376516.2011.610388&partnerID=40&md5=26eb2e93774a1e17d9d4c631e03bf4a6}, doi = {10.3109/15376516.2011.610388}, year = {2012}, date = {2012-01-01}, journal = {Toxicology Mechanisms and Methods}, volume = {22}, number = {2}, pages = {159-160}, abstract = {A "foam cone" exuding the mouth and nostrils is a recognized consequence of anoxia following pulmonary edema. In this report, we illustrate and explain this phenomenon in victims of heroin overdose. © 2012 Informa Healthcare USA, Inc.}, note = {cited By 17}, keywords = {}, pubstate = {published}, tppubtype = {article} } A "foam cone" exuding the mouth and nostrils is a recognized consequence of anoxia following pulmonary edema. In this report, we illustrate and explain this phenomenon in victims of heroin overdose. © 2012 Informa Healthcare USA, Inc. |
Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Proença, J B; Santos, A; Magalhães, T Clinical and forensic signs related to cocaine abuse Journal Article Current Drug Abuse Reviews, 5 (1), pp. 64-83, 2012, (cited By 22). @article{Dinis-Oliveira201264b, title = {Clinical and forensic signs related to cocaine abuse}, author = {R J Dinis-Oliveira and F Carvalho and J A Duarte and J B Proença and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84860286519&doi=10.2174%2f1874473711205010064&partnerID=40&md5=906cc1a2aa1590223bc371b16a21f838}, doi = {10.2174/1874473711205010064}, year = {2012}, date = {2012-01-01}, journal = {Current Drug Abuse Reviews}, volume = {5}, number = {1}, pages = {64-83}, abstract = {Good laboratory practice in toxicological analysis requires pre-analytical steps for collection of detailed information related to the suspected poisoning episodes, including biological and non-biological circumstantial evidences, which should be carefully scrutinized. This procedure provides great help to unveil the suspected cause of poisoning, to select the appropriate and correct samples to be analyzed and can facilitate the decision about the analytical techniques to perform. This implies a good knowledge of the signs related to acute and chronic intoxications by drugs of abuse. In this manuscript we highlight and discuss clinical and forensic imaging related to cocaine abuse, namely the midline destructive lesion, dental health, pseudoscleradermatous triad and crack hands, necrosis and gangrene of extremities and several other skin manifestations, reticular purpura, intracerebral and peripheral hemorrhages, angioneurotic edema, rhabdomyolysis, and crack lung. For this purpose, the state of the art on this topic is discussed, using clinical and forensic cases from our professional database in complement to images and mechanistic data from literature. © 2012 Bentham Science Publishers.}, note = {cited By 22}, keywords = {}, pubstate = {published}, tppubtype = {article} } Good laboratory practice in toxicological analysis requires pre-analytical steps for collection of detailed information related to the suspected poisoning episodes, including biological and non-biological circumstantial evidences, which should be carefully scrutinized. This procedure provides great help to unveil the suspected cause of poisoning, to select the appropriate and correct samples to be analyzed and can facilitate the decision about the analytical techniques to perform. This implies a good knowledge of the signs related to acute and chronic intoxications by drugs of abuse. In this manuscript we highlight and discuss clinical and forensic imaging related to cocaine abuse, namely the midline destructive lesion, dental health, pseudoscleradermatous triad and crack hands, necrosis and gangrene of extremities and several other skin manifestations, reticular purpura, intracerebral and peripheral hemorrhages, angioneurotic edema, rhabdomyolysis, and crack lung. For this purpose, the state of the art on this topic is discussed, using clinical and forensic cases from our professional database in complement to images and mechanistic data from literature. © 2012 Bentham Science Publishers. |
2011 |
Silva, R; Carmo, H; Dinis-Oliveira, R; Cordeiro-Da-Silva, A; Lima, S C; Carvalho, F; Bastos, De Lourdes M; Remião, F In vitro study of P-glycoprotein induction as an antidotal pathway to prevent cytotoxicity in Caco-2 cells Journal Article 85 (4), pp. 315-326, 2011, (cited By 34). @article{Silva2011315, title = {In vitro study of P-glycoprotein induction as an antidotal pathway to prevent cytotoxicity in Caco-2 cells}, author = {R Silva and H Carmo and R Dinis-Oliveira and A Cordeiro-Da-Silva and S C Lima and F Carvalho and M De Lourdes Bastos and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79954426149&doi=10.1007%2fs00204-010-0587-8&partnerID=40&md5=47274717d53d5eff3d8748a53a2b49b2}, doi = {10.1007/s00204-010-0587-8}, year = {2011}, date = {2011-01-01}, volume = {85}, number = {4}, pages = {315-326}, abstract = {The Caco-2 cell line is a reliable in vitro model for predicting drug intestinal absorption and P-glycoprotein (P-gp)-mediated excretion in humans. Recent in vivo studies suggested the induction of P-gp as a cellular protection tool against paraquat poisoning, through the increase in its pulmonary and intestinal excretion. Thus, the aim of the present work was to evaluate P-gp expression and activity in Caco-2 cells exposed to doxorubicin (a known P-gp inducer) and to correlate these changes with paraquat toxic effects. Cytotoxicity of doxorubicin (0-100 μM) and paraquat (0-1,000 μM) was evaluated for a maximum period of 96 h. In doxorubicin-exposed cells, P-gp expression and transport activity were evaluated by flow cytometry, using a fluorescein isothiocyanate-conjugated antibody and the P-gp fluorescent subtract rhodamine 123, respectively. A significant increase in P-gp expression was observed as soon as 6 h after exposure to 5 μM doxorubicin. P-gp activity also increased after 6 h, but only at higher doxorubicin concentrations (over 50 μM). Paraquat (0-5,000 μM) cytotoxicity was then evaluated with or without previous exposure of the cells to doxorubicin (5-100 μM, a concentration range causing both an increase in P-gp expression and activity). Under P-gp induction, a significant reduction in paraquat cytotoxicity was observed. Furthermore, when these cells were incubated with a specific P-gp inhibitor (UIC2 antibody) the doxorubicin protective effects were blocked, confirming the involvement of P-gp in the reduction in paraquat cytotoxicity. In conclusion, the human Caco-2 cell line model can be used for the study of P-gp induction as an antidotal pathway against substrates of this transporter system. © 2010 Springer-Verlag.}, note = {cited By 34}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Caco-2 cell line is a reliable in vitro model for predicting drug intestinal absorption and P-glycoprotein (P-gp)-mediated excretion in humans. Recent in vivo studies suggested the induction of P-gp as a cellular protection tool against paraquat poisoning, through the increase in its pulmonary and intestinal excretion. Thus, the aim of the present work was to evaluate P-gp expression and activity in Caco-2 cells exposed to doxorubicin (a known P-gp inducer) and to correlate these changes with paraquat toxic effects. Cytotoxicity of doxorubicin (0-100 μM) and paraquat (0-1,000 μM) was evaluated for a maximum period of 96 h. In doxorubicin-exposed cells, P-gp expression and transport activity were evaluated by flow cytometry, using a fluorescein isothiocyanate-conjugated antibody and the P-gp fluorescent subtract rhodamine 123, respectively. A significant increase in P-gp expression was observed as soon as 6 h after exposure to 5 μM doxorubicin. P-gp activity also increased after 6 h, but only at higher doxorubicin concentrations (over 50 μM). Paraquat (0-5,000 μM) cytotoxicity was then evaluated with or without previous exposure of the cells to doxorubicin (5-100 μM, a concentration range causing both an increase in P-gp expression and activity). Under P-gp induction, a significant reduction in paraquat cytotoxicity was observed. Furthermore, when these cells were incubated with a specific P-gp inhibitor (UIC2 antibody) the doxorubicin protective effects were blocked, confirming the involvement of P-gp in the reduction in paraquat cytotoxicity. In conclusion, the human Caco-2 cell line model can be used for the study of P-gp induction as an antidotal pathway against substrates of this transporter system. © 2010 Springer-Verlag. |
Baltazar, M T; Dinis-Oliveira, R J; Duarte, J A; Bastos, M L; Carvalho, F Antioxidant properties and associated mechanisms of salicylates Journal Article 18 (21), pp. 3252-3264, 2011, (cited By 18). @article{Baltazar20113252, title = {Antioxidant properties and associated mechanisms of salicylates}, author = {M T Baltazar and R J Dinis-Oliveira and J A Duarte and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79959996651&doi=10.2174%2f092986711796391552&partnerID=40&md5=cd5d9b66e4bd575301804a107e4efcbb}, doi = {10.2174/092986711796391552}, year = {2011}, date = {2011-01-01}, volume = {18}, number = {21}, pages = {3252-3264}, abstract = {The pharmacological action of salicylates has been historically related to their ability to inhibit cyclooxygenases, thereby blocking the synthesis of prostaglandins and thromboxane A2. On the other hand, several studies have suggested that salicylates have a multitude of cyclooxygenase-independent actions specially related with their antioxidant properties, which might contribute to the overall salutary effects of these compounds. Although salicylates are well-known antioxidants through their ability to scavenge hydroxyl radical, their antioxidant mechanisms of action have not been fully compiled and characterized. In this context, several mechanisms of action have been suggested, namely i) scavenging of hydroxyl radical and chelation of transition metals; ii) upregulation of nitric oxide; iii) increased synthesis of lipoxins; iv) inhibition of neutrophil oxidative burst; v) inhibition of NF-κP-1 protein kinases; and vii) inhibiton of lectin-like oxidized LDL receptor-1. The newly discovered acetyl salicylic acid-triggered lipoxins probably play a key role in the maintenance of the oxidative stress balance. Furthermore, salicylates have shown to protect low-density lipoprotein from oxidation and elicit an inhibitory effect on the expression of lectin-like receptors on endothelial cells. This review aims to provide an overview of the various proposed antioxidant mechanisms of salicylates. © 2011 Bentham Science Publishers Ltd.}, note = {cited By 18}, keywords = {}, pubstate = {published}, tppubtype = {article} } The pharmacological action of salicylates has been historically related to their ability to inhibit cyclooxygenases, thereby blocking the synthesis of prostaglandins and thromboxane A2. On the other hand, several studies have suggested that salicylates have a multitude of cyclooxygenase-independent actions specially related with their antioxidant properties, which might contribute to the overall salutary effects of these compounds. Although salicylates are well-known antioxidants through their ability to scavenge hydroxyl radical, their antioxidant mechanisms of action have not been fully compiled and characterized. In this context, several mechanisms of action have been suggested, namely i) scavenging of hydroxyl radical and chelation of transition metals; ii) upregulation of nitric oxide; iii) increased synthesis of lipoxins; iv) inhibition of neutrophil oxidative burst; v) inhibition of NF-κP-1 protein kinases; and vii) inhibiton of lectin-like oxidized LDL receptor-1. The newly discovered acetyl salicylic acid-triggered lipoxins probably play a key role in the maintenance of the oxidative stress balance. Furthermore, salicylates have shown to protect low-density lipoprotein from oxidation and elicit an inhibitory effect on the expression of lectin-like receptors on endothelial cells. This review aims to provide an overview of the various proposed antioxidant mechanisms of salicylates. © 2011 Bentham Science Publishers Ltd. |
Silva, R; Carmo, H; Dinis-Oliveira, R; Cordeiro-Da-Silva, A; Lima, S C; Carvalho, F; Bastos, De Lourdes M; Remião, F In vitro study of P-glycoprotein induction as an antidotal pathway to prevent cytotoxicity in Caco-2 cells Journal Article Archives of Toxicology, 85 (4), pp. 315-326, 2011, (cited By 37). @article{Silva2011315b, title = {In vitro study of P-glycoprotein induction as an antidotal pathway to prevent cytotoxicity in Caco-2 cells}, author = {R Silva and H Carmo and R Dinis-Oliveira and A Cordeiro-Da-Silva and S C Lima and F Carvalho and M De Lourdes Bastos and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79954426149&doi=10.1007%2fs00204-010-0587-8&partnerID=40&md5=47274717d53d5eff3d8748a53a2b49b2}, doi = {10.1007/s00204-010-0587-8}, year = {2011}, date = {2011-01-01}, journal = {Archives of Toxicology}, volume = {85}, number = {4}, pages = {315-326}, abstract = {The Caco-2 cell line is a reliable in vitro model for predicting drug intestinal absorption and P-glycoprotein (P-gp)-mediated excretion in humans. Recent in vivo studies suggested the induction of P-gp as a cellular protection tool against paraquat poisoning, through the increase in its pulmonary and intestinal excretion. Thus, the aim of the present work was to evaluate P-gp expression and activity in Caco-2 cells exposed to doxorubicin (a known P-gp inducer) and to correlate these changes with paraquat toxic effects. Cytotoxicity of doxorubicin (0-100 μM) and paraquat (0-1,000 μM) was evaluated for a maximum period of 96 h. In doxorubicin-exposed cells, P-gp expression and transport activity were evaluated by flow cytometry, using a fluorescein isothiocyanate-conjugated antibody and the P-gp fluorescent subtract rhodamine 123, respectively. A significant increase in P-gp expression was observed as soon as 6 h after exposure to 5 μM doxorubicin. P-gp activity also increased after 6 h, but only at higher doxorubicin concentrations (over 50 μM). Paraquat (0-5,000 μM) cytotoxicity was then evaluated with or without previous exposure of the cells to doxorubicin (5-100 μM, a concentration range causing both an increase in P-gp expression and activity). Under P-gp induction, a significant reduction in paraquat cytotoxicity was observed. Furthermore, when these cells were incubated with a specific P-gp inhibitor (UIC2 antibody) the doxorubicin protective effects were blocked, confirming the involvement of P-gp in the reduction in paraquat cytotoxicity. In conclusion, the human Caco-2 cell line model can be used for the study of P-gp induction as an antidotal pathway against substrates of this transporter system. © 2010 Springer-Verlag.}, note = {cited By 37}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Caco-2 cell line is a reliable in vitro model for predicting drug intestinal absorption and P-glycoprotein (P-gp)-mediated excretion in humans. Recent in vivo studies suggested the induction of P-gp as a cellular protection tool against paraquat poisoning, through the increase in its pulmonary and intestinal excretion. Thus, the aim of the present work was to evaluate P-gp expression and activity in Caco-2 cells exposed to doxorubicin (a known P-gp inducer) and to correlate these changes with paraquat toxic effects. Cytotoxicity of doxorubicin (0-100 μM) and paraquat (0-1,000 μM) was evaluated for a maximum period of 96 h. In doxorubicin-exposed cells, P-gp expression and transport activity were evaluated by flow cytometry, using a fluorescein isothiocyanate-conjugated antibody and the P-gp fluorescent subtract rhodamine 123, respectively. A significant increase in P-gp expression was observed as soon as 6 h after exposure to 5 μM doxorubicin. P-gp activity also increased after 6 h, but only at higher doxorubicin concentrations (over 50 μM). Paraquat (0-5,000 μM) cytotoxicity was then evaluated with or without previous exposure of the cells to doxorubicin (5-100 μM, a concentration range causing both an increase in P-gp expression and activity). Under P-gp induction, a significant reduction in paraquat cytotoxicity was observed. Furthermore, when these cells were incubated with a specific P-gp inhibitor (UIC2 antibody) the doxorubicin protective effects were blocked, confirming the involvement of P-gp in the reduction in paraquat cytotoxicity. In conclusion, the human Caco-2 cell line model can be used for the study of P-gp induction as an antidotal pathway against substrates of this transporter system. © 2010 Springer-Verlag. |
Baltazar, M T; Dinis-Oliveira, R J; Duarte, J A; Bastos, M L; Carvalho, F Antioxidant properties and associated mechanisms of salicylates Journal Article Current Medicinal Chemistry, 18 (21), pp. 3252-3264, 2011, (cited By 21). @article{Baltazar20113252b, title = {Antioxidant properties and associated mechanisms of salicylates}, author = {M T Baltazar and R J Dinis-Oliveira and J A Duarte and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79959996651&doi=10.2174%2f092986711796391552&partnerID=40&md5=cd5d9b66e4bd575301804a107e4efcbb}, doi = {10.2174/092986711796391552}, year = {2011}, date = {2011-01-01}, journal = {Current Medicinal Chemistry}, volume = {18}, number = {21}, pages = {3252-3264}, abstract = {The pharmacological action of salicylates has been historically related to their ability to inhibit cyclooxygenases, thereby blocking the synthesis of prostaglandins and thromboxane A2. On the other hand, several studies have suggested that salicylates have a multitude of cyclooxygenase-independent actions specially related with their antioxidant properties, which might contribute to the overall salutary effects of these compounds. Although salicylates are well-known antioxidants through their ability to scavenge hydroxyl radical, their antioxidant mechanisms of action have not been fully compiled and characterized. In this context, several mechanisms of action have been suggested, namely i) scavenging of hydroxyl radical and chelation of transition metals; ii) upregulation of nitric oxide; iii) increased synthesis of lipoxins; iv) inhibition of neutrophil oxidative burst; v) inhibition of NF-κP-1 protein kinases; and vii) inhibiton of lectin-like oxidized LDL receptor-1. The newly discovered acetyl salicylic acid-triggered lipoxins probably play a key role in the maintenance of the oxidative stress balance. Furthermore, salicylates have shown to protect low-density lipoprotein from oxidation and elicit an inhibitory effect on the expression of lectin-like receptors on endothelial cells. This review aims to provide an overview of the various proposed antioxidant mechanisms of salicylates. © 2011 Bentham Science Publishers Ltd.}, note = {cited By 21}, keywords = {}, pubstate = {published}, tppubtype = {article} } The pharmacological action of salicylates has been historically related to their ability to inhibit cyclooxygenases, thereby blocking the synthesis of prostaglandins and thromboxane A2. On the other hand, several studies have suggested that salicylates have a multitude of cyclooxygenase-independent actions specially related with their antioxidant properties, which might contribute to the overall salutary effects of these compounds. Although salicylates are well-known antioxidants through their ability to scavenge hydroxyl radical, their antioxidant mechanisms of action have not been fully compiled and characterized. In this context, several mechanisms of action have been suggested, namely i) scavenging of hydroxyl radical and chelation of transition metals; ii) upregulation of nitric oxide; iii) increased synthesis of lipoxins; iv) inhibition of neutrophil oxidative burst; v) inhibition of NF-κP-1 protein kinases; and vii) inhibiton of lectin-like oxidized LDL receptor-1. The newly discovered acetyl salicylic acid-triggered lipoxins probably play a key role in the maintenance of the oxidative stress balance. Furthermore, salicylates have shown to protect low-density lipoprotein from oxidation and elicit an inhibitory effect on the expression of lectin-like receptors on endothelial cells. This review aims to provide an overview of the various proposed antioxidant mechanisms of salicylates. © 2011 Bentham Science Publishers Ltd. |
2010 |
Dinis-Oliveira, Jorge R; Carvalho, F; Magalhães, T; Santos, A Postmortem changes in carbon monoxide poisoning Journal Article 48 (7), pp. 762-763, 2010, (cited By 5). @article{JorgeDinis-Oliveira2010762, title = {Postmortem changes in carbon monoxide poisoning}, author = {R Jorge Dinis-Oliveira and F Carvalho and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77956997432&doi=10.3109%2f15563650.2010.484394&partnerID=40&md5=6fe60e65ef89f6b6e8a0c8708d6d5fc1}, doi = {10.3109/15563650.2010.484394}, year = {2010}, date = {2010-01-01}, volume = {48}, number = {7}, pages = {762-763}, note = {cited By 5}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dinis-Oliveira, R J; Caldas, I; Carvalho, F; Magalhães, T Bruxism after 3,4-methylenedioxymethamphetamine (ecstasy) abuse Journal Article 48 (8), pp. 863-864, 2010, (cited By 12). @article{Dinis-Oliveira2010863, title = {Bruxism after 3,4-methylenedioxymethamphetamine (ecstasy) abuse}, author = {R J Dinis-Oliveira and I Caldas and F Carvalho and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77958615861&doi=10.3109%2f15563650.2010.489903&partnerID=40&md5=50453492d50bfd01f1731610014eb801}, doi = {10.3109/15563650.2010.489903}, year = {2010}, date = {2010-01-01}, volume = {48}, number = {8}, pages = {863-864}, abstract = {Bruxism is a recognized side effect of several licit and illicit drugs. In this report, we illustrate this phenomenon in three patients suffering from 3,4-methylenedioxymethamphetamine (ecstasy) abuse. © 2010 Informa UK, Ltd.}, note = {cited By 12}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bruxism is a recognized side effect of several licit and illicit drugs. In this report, we illustrate this phenomenon in three patients suffering from 3,4-methylenedioxymethamphetamine (ecstasy) abuse. © 2010 Informa UK, Ltd. |
Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Remião, F; Marques, A; Santos, A; Magalhães, T Collection of biological samples in forensic toxicology Journal Article 20 (7), pp. 363-414, 2010, (cited By 56). @article{Dinis-Oliveira2010363, title = {Collection of biological samples in forensic toxicology}, author = {R J Dinis-Oliveira and F Carvalho and J A Duarte and F Remião and A Marques and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77955898529&doi=10.3109%2f15376516.2010.497976&partnerID=40&md5=31b5acba1ffc0788f55cce3ba1781815}, doi = {10.3109/15376516.2010.497976}, year = {2010}, date = {2010-01-01}, volume = {20}, number = {7}, pages = {363-414}, abstract = {Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission. © 2010 Informa Healthcare USA, Inc.}, note = {cited By 56}, keywords = {}, pubstate = {published}, tppubtype = {article} } Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission. © 2010 Informa Healthcare USA, Inc. |
Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Dias, R; Magalhães, T; Santos, A Suicide by hanging under the influence of ketamine and ethanol Journal Article 202 (1-3), pp. e23-e27, 2010, (cited By 10). @article{Dinis-Oliveira2010d, title = {Suicide by hanging under the influence of ketamine and ethanol}, author = {R J Dinis-Oliveira and F Carvalho and J A Duarte and R Dias and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955101917&doi=10.1016%2fj.forsciint.2010.04.047&partnerID=40&md5=c29fe97172cd73f813081846782c5d58}, doi = {10.1016/j.forsciint.2010.04.047}, year = {2010}, date = {2010-01-01}, volume = {202}, number = {1-3}, pages = {e23-e27}, abstract = {Psychiatric deviations resulting from alcohol and illegal drug abuse may be considered a major risk factor for suicidal behavior. This report describes a suicide by hanging, under the influence of ketamine and alcohol. The victim was a 29-year-old man, found dead hanging by the neck from a metallic beam in the ceiling of his workplace. Besides characteristic signs of hanging seen at the autopsy, toxicological analysis revealed a femoral blood concentration of ketamine and ethanol of 1.3. mg/L and 0.66. g/L, respectively. Positive qualitative results for ketamine were also detected, in a powder found near the victim and on the victim's nostrils, which suggests nasal inhaling as administration route. The hallucinogenic effects caused by ketamine, associated with an increased sensitivity of N-methyl-d-aspartate (NMDA) receptors to ketamine as result of the previous history of alcoholism should be considered as potential inducing factors in suicide behaviors. © 2010 Elsevier Ireland Ltd.}, note = {cited By 10}, keywords = {}, pubstate = {published}, tppubtype = {article} } Psychiatric deviations resulting from alcohol and illegal drug abuse may be considered a major risk factor for suicidal behavior. This report describes a suicide by hanging, under the influence of ketamine and alcohol. The victim was a 29-year-old man, found dead hanging by the neck from a metallic beam in the ceiling of his workplace. Besides characteristic signs of hanging seen at the autopsy, toxicological analysis revealed a femoral blood concentration of ketamine and ethanol of 1.3. mg/L and 0.66. g/L, respectively. Positive qualitative results for ketamine were also detected, in a powder found near the victim and on the victim's nostrils, which suggests nasal inhaling as administration route. The hallucinogenic effects caused by ketamine, associated with an increased sensitivity of N-methyl-d-aspartate (NMDA) receptors to ketamine as result of the previous history of alcoholism should be considered as potential inducing factors in suicide behaviors. © 2010 Elsevier Ireland Ltd. |
Dinis-Oliveira, R J; Nunes, R; Carvalho, F; Santos, A; Teixeira, H; Vieira, D N; Magalhães, T 23 (6), pp. 1059-1082, 2010, (cited By 3). @article{Dinis-Oliveira20101059, title = {Ethical, technical and legal procedures of the medical doctor responsibility: To accomplish the road enforcement law about driving under the influence of alcohol and psychotropic substances [Procedimentos técnicos, éticos e legais da competência do médico: No cumprimento da lei da fiscalização da condução rodoviária sob influência do álcool e substâncias psicotrópicas]}, author = {R J Dinis-Oliveira and R Nunes and F Carvalho and A Santos and H Teixeira and D N Vieira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78751557858&partnerID=40&md5=c4a23dde87fffae21aa3c16b4a2f2806}, year = {2010}, date = {2010-01-01}, volume = {23}, number = {6}, pages = {1059-1082}, abstract = {The Forensic Toxicology (TF) is a science of analytical basis, aiming to clarify legal issues related to poisoning, whether or not fatal, within the various areas of law (criminal, civil, labor, etc.). The analysis that are more often requested (with a tendency to increase and gaining rising attention) are those concerning the procedures involving supervision of driving under the influence of alcohol and psychotropic substances, in the living individual and in the cadaver. The key players in this process, are: (a) the police agents carrying out the screening and quantification of alcohol on the exhaled breath and the screening of psychotropic and stupefacient substances in saliva; (b) the public health services that perform qualitative analysis of these substances in urine (if the test was not previously performed in saliva); (c) the doctor that collects blood samples from the living, or the dead victim; (d) the forensic toxicologist who conducts toxicological analysis in blood (or, eventually in another biological sample) and (e) the magistrate prosecutors that ultimately will receive the toxicological report to apply the Law. Therefore it is important to understand and be acquainted with the road law enforcement of driving under the influence of alcohol and psychotropic substances, particularly in what concerns to the role ofthe medical doctor. Consequently, this paper aimed to review these topics, namely highlighting the necessary information to clarify the interested parties about the technical, ethical and legal procedures to consider. © 2010 CELOM.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Forensic Toxicology (TF) is a science of analytical basis, aiming to clarify legal issues related to poisoning, whether or not fatal, within the various areas of law (criminal, civil, labor, etc.). The analysis that are more often requested (with a tendency to increase and gaining rising attention) are those concerning the procedures involving supervision of driving under the influence of alcohol and psychotropic substances, in the living individual and in the cadaver. The key players in this process, are: (a) the police agents carrying out the screening and quantification of alcohol on the exhaled breath and the screening of psychotropic and stupefacient substances in saliva; (b) the public health services that perform qualitative analysis of these substances in urine (if the test was not previously performed in saliva); (c) the doctor that collects blood samples from the living, or the dead victim; (d) the forensic toxicologist who conducts toxicological analysis in blood (or, eventually in another biological sample) and (e) the magistrate prosecutors that ultimately will receive the toxicological report to apply the Law. Therefore it is important to understand and be acquainted with the road law enforcement of driving under the influence of alcohol and psychotropic substances, particularly in what concerns to the role ofthe medical doctor. Consequently, this paper aimed to review these topics, namely highlighting the necessary information to clarify the interested parties about the technical, ethical and legal procedures to consider. © 2010 CELOM. |
Dinis-Oliveira, R J; Nunes, R; Carvalho, F; Santos, A; Teixeira, H; Vieira, D N; Magalhães, T Acta Medica Portuguesa, 23 (6), pp. 1059-1082, 2010, (cited By 3). @article{Dinis-Oliveira20101059b, title = {Ethical, technical and legal procedures of the medical doctor responsibility: To accomplish the road enforcement law about driving under the influence of alcohol and psychotropic substances [Procedimentos técnicos, éticos e legais da competência do médico: No cumprimento da lei da fiscalização da condução rodoviária sob influência do álcool e substâncias psicotrópicas]}, author = {R J Dinis-Oliveira and R Nunes and F Carvalho and A Santos and H Teixeira and D N Vieira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78751557858&partnerID=40&md5=c4a23dde87fffae21aa3c16b4a2f2806}, year = {2010}, date = {2010-01-01}, journal = {Acta Medica Portuguesa}, volume = {23}, number = {6}, pages = {1059-1082}, abstract = {The Forensic Toxicology (TF) is a science of analytical basis, aiming to clarify legal issues related to poisoning, whether or not fatal, within the various areas of law (criminal, civil, labor, etc.). The analysis that are more often requested (with a tendency to increase and gaining rising attention) are those concerning the procedures involving supervision of driving under the influence of alcohol and psychotropic substances, in the living individual and in the cadaver. The key players in this process, are: (a) the police agents carrying out the screening and quantification of alcohol on the exhaled breath and the screening of psychotropic and stupefacient substances in saliva; (b) the public health services that perform qualitative analysis of these substances in urine (if the test was not previously performed in saliva); (c) the doctor that collects blood samples from the living, or the dead victim; (d) the forensic toxicologist who conducts toxicological analysis in blood (or, eventually in another biological sample) and (e) the magistrate prosecutors that ultimately will receive the toxicological report to apply the Law. Therefore it is important to understand and be acquainted with the road law enforcement of driving under the influence of alcohol and psychotropic substances, particularly in what concerns to the role ofthe medical doctor. Consequently, this paper aimed to review these topics, namely highlighting the necessary information to clarify the interested parties about the technical, ethical and legal procedures to consider. © 2010 CELOM.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Forensic Toxicology (TF) is a science of analytical basis, aiming to clarify legal issues related to poisoning, whether or not fatal, within the various areas of law (criminal, civil, labor, etc.). The analysis that are more often requested (with a tendency to increase and gaining rising attention) are those concerning the procedures involving supervision of driving under the influence of alcohol and psychotropic substances, in the living individual and in the cadaver. The key players in this process, are: (a) the police agents carrying out the screening and quantification of alcohol on the exhaled breath and the screening of psychotropic and stupefacient substances in saliva; (b) the public health services that perform qualitative analysis of these substances in urine (if the test was not previously performed in saliva); (c) the doctor that collects blood samples from the living, or the dead victim; (d) the forensic toxicologist who conducts toxicological analysis in blood (or, eventually in another biological sample) and (e) the magistrate prosecutors that ultimately will receive the toxicological report to apply the Law. Therefore it is important to understand and be acquainted with the road law enforcement of driving under the influence of alcohol and psychotropic substances, particularly in what concerns to the role ofthe medical doctor. Consequently, this paper aimed to review these topics, namely highlighting the necessary information to clarify the interested parties about the technical, ethical and legal procedures to consider. © 2010 CELOM. |
Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Dias, R; Magalhães, T; Santos, A Suicide by hanging under the influence of ketamine and ethanol Journal Article Forensic Science International, 202 (1-3), pp. e23-e27, 2010, (cited By 12). @article{Dinis-Oliveira2010g, title = {Suicide by hanging under the influence of ketamine and ethanol}, author = {R J Dinis-Oliveira and F Carvalho and J A Duarte and R Dias and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955101917&doi=10.1016%2fj.forsciint.2010.04.047&partnerID=40&md5=c29fe97172cd73f813081846782c5d58}, doi = {10.1016/j.forsciint.2010.04.047}, year = {2010}, date = {2010-01-01}, journal = {Forensic Science International}, volume = {202}, number = {1-3}, pages = {e23-e27}, abstract = {Psychiatric deviations resulting from alcohol and illegal drug abuse may be considered a major risk factor for suicidal behavior. This report describes a suicide by hanging, under the influence of ketamine and alcohol. The victim was a 29-year-old man, found dead hanging by the neck from a metallic beam in the ceiling of his workplace. Besides characteristic signs of hanging seen at the autopsy, toxicological analysis revealed a femoral blood concentration of ketamine and ethanol of 1.3. mg/L and 0.66. g/L, respectively. Positive qualitative results for ketamine were also detected, in a powder found near the victim and on the victim's nostrils, which suggests nasal inhaling as administration route. The hallucinogenic effects caused by ketamine, associated with an increased sensitivity of N-methyl-d-aspartate (NMDA) receptors to ketamine as result of the previous history of alcoholism should be considered as potential inducing factors in suicide behaviors. © 2010 Elsevier Ireland Ltd.}, note = {cited By 12}, keywords = {}, pubstate = {published}, tppubtype = {article} } Psychiatric deviations resulting from alcohol and illegal drug abuse may be considered a major risk factor for suicidal behavior. This report describes a suicide by hanging, under the influence of ketamine and alcohol. The victim was a 29-year-old man, found dead hanging by the neck from a metallic beam in the ceiling of his workplace. Besides characteristic signs of hanging seen at the autopsy, toxicological analysis revealed a femoral blood concentration of ketamine and ethanol of 1.3. mg/L and 0.66. g/L, respectively. Positive qualitative results for ketamine were also detected, in a powder found near the victim and on the victim's nostrils, which suggests nasal inhaling as administration route. The hallucinogenic effects caused by ketamine, associated with an increased sensitivity of N-methyl-d-aspartate (NMDA) receptors to ketamine as result of the previous history of alcoholism should be considered as potential inducing factors in suicide behaviors. © 2010 Elsevier Ireland Ltd. |
Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Remião, F; Marques, A; Santos, A; Magalhães, T Collection of biological samples in forensic toxicology Journal Article Toxicology Mechanisms and Methods, 20 (7), pp. 363-414, 2010, (cited By 68). @article{Dinis-Oliveira2010363b, title = {Collection of biological samples in forensic toxicology}, author = {R J Dinis-Oliveira and F Carvalho and J A Duarte and F Remião and A Marques and A Santos and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77955898529&doi=10.3109%2f15376516.2010.497976&partnerID=40&md5=31b5acba1ffc0788f55cce3ba1781815}, doi = {10.3109/15376516.2010.497976}, year = {2010}, date = {2010-01-01}, journal = {Toxicology Mechanisms and Methods}, volume = {20}, number = {7}, pages = {363-414}, abstract = {Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission. © 2010 Informa Healthcare USA, Inc.}, note = {cited By 68}, keywords = {}, pubstate = {published}, tppubtype = {article} } Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission. © 2010 Informa Healthcare USA, Inc. |
Dinis-Oliveira, R J; Caldas, I; Carvalho, F; Magalhães, T Bruxism after 3,4-methylenedioxymethamphetamine (ecstasy) abuse Journal Article Clinical Toxicology, 48 (8), pp. 863-864, 2010, (cited By 14). @article{Dinis-Oliveira2010863b, title = {Bruxism after 3,4-methylenedioxymethamphetamine (ecstasy) abuse}, author = {R J Dinis-Oliveira and I Caldas and F Carvalho and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77958615861&doi=10.3109%2f15563650.2010.489903&partnerID=40&md5=50453492d50bfd01f1731610014eb801}, doi = {10.3109/15563650.2010.489903}, year = {2010}, date = {2010-01-01}, journal = {Clinical Toxicology}, volume = {48}, number = {8}, pages = {863-864}, abstract = {Bruxism is a recognized side effect of several licit and illicit drugs. In this report, we illustrate this phenomenon in three patients suffering from 3,4-methylenedioxymethamphetamine (ecstasy) abuse. © 2010 Informa UK, Ltd.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bruxism is a recognized side effect of several licit and illicit drugs. In this report, we illustrate this phenomenon in three patients suffering from 3,4-methylenedioxymethamphetamine (ecstasy) abuse. © 2010 Informa UK, Ltd. |
Dinis-Oliveira, Jorge R; Carvalho, F; Magalhães, T; Santos, A Postmortem changes in carbon monoxide poisoning Journal Article Clinical Toxicology, 48 (7), pp. 762-763, 2010, (cited By 5). @article{JorgeDinis-Oliveira2010762b, title = {Postmortem changes in carbon monoxide poisoning}, author = {R Jorge Dinis-Oliveira and F Carvalho and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77956997432&doi=10.3109%2f15563650.2010.484394&partnerID=40&md5=6fe60e65ef89f6b6e8a0c8708d6d5fc1}, doi = {10.3109/15563650.2010.484394}, year = {2010}, date = {2010-01-01}, journal = {Clinical Toxicology}, volume = {48}, number = {7}, pages = {762-763}, note = {cited By 5}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2009 |
Dinis-Oliveira, R J; Pontes, H; Bastos, M L; Remião, F; Duarte, J A; Carvalho, F An effective antidote for paraquat poisonings: The treatment with lysine acetylsalicylate Journal Article 255 (3), pp. 187-193, 2009, (cited By 35). @article{Dinis-Oliveira2009187, title = {An effective antidote for paraquat poisonings: The treatment with lysine acetylsalicylate}, author = {R J Dinis-Oliveira and H Pontes and M L Bastos and F Remião and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-58149157786&doi=10.1016%2fj.tox.2008.10.015&partnerID=40&md5=0a47a85733fc009f2d108a5d54a08a69}, doi = {10.1016/j.tox.2008.10.015}, year = {2009}, date = {2009-01-01}, volume = {255}, number = {3}, pages = {187-193}, abstract = {Sodium salicylate (NaSAL) has been shown to have a multifactorial protection mechanism against paraquat (PQ)-induced toxicity, due to its ability to modulate inflammatory signalling systems, to prevent oxidative stress and to its capacity to chelate PQ. Considering that currently there is no pharmaceutical formulation available for parenteral administration of NaSAL, the aim of the present study was to evaluate the antidotal feasibility of a salicylate prodrug, lysine acetylsalicylate (LAS), accessible for parenteral administrations. PQ was administered to Wistar rats by gavage (125 mg/kg of PQ ion) and the treatment was performed intraperitoneally with different doses (100, 200 and 400 mg/kg of body weight) of LAS. Survival rate was followed during 30 days and living animals at this endpoint were sacrificed for lung, kidney, liver, jejune and heart histological analysis. It was shown, that the salicylate prodrug, LAS, available in a large number of hospitals, is also effective in the treatment of PQ intoxications. From all tested LAS doses, 200 mg/kg assured animal's full survival. Comparatively to 60% of mortality observed in PQ only exposed animals, the lethality was higher (80%) in the group that received 400 mg/kg of LAS 2 h after PQ administration. The dose of 100 mg/kg of LAS showed only a modest protection (60% of survival). Collagen deposition was observed by histological analysis in survived animals of all experimental groups, being less pronounced in animals receiving 200 mg/kg of LAS, reinforcing the importance of this dose against tissue damage induced by PQ. The results allow us to suggest that LAS should be considered in the hospital treatment of PQ poisonings. © 2008 Elsevier Ireland Ltd. All rights reserved.}, note = {cited By 35}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sodium salicylate (NaSAL) has been shown to have a multifactorial protection mechanism against paraquat (PQ)-induced toxicity, due to its ability to modulate inflammatory signalling systems, to prevent oxidative stress and to its capacity to chelate PQ. Considering that currently there is no pharmaceutical formulation available for parenteral administration of NaSAL, the aim of the present study was to evaluate the antidotal feasibility of a salicylate prodrug, lysine acetylsalicylate (LAS), accessible for parenteral administrations. PQ was administered to Wistar rats by gavage (125 mg/kg of PQ ion) and the treatment was performed intraperitoneally with different doses (100, 200 and 400 mg/kg of body weight) of LAS. Survival rate was followed during 30 days and living animals at this endpoint were sacrificed for lung, kidney, liver, jejune and heart histological analysis. It was shown, that the salicylate prodrug, LAS, available in a large number of hospitals, is also effective in the treatment of PQ intoxications. From all tested LAS doses, 200 mg/kg assured animal's full survival. Comparatively to 60% of mortality observed in PQ only exposed animals, the lethality was higher (80%) in the group that received 400 mg/kg of LAS 2 h after PQ administration. The dose of 100 mg/kg of LAS showed only a modest protection (60% of survival). Collagen deposition was observed by histological analysis in survived animals of all experimental groups, being less pronounced in animals receiving 200 mg/kg of LAS, reinforcing the importance of this dose against tissue damage induced by PQ. The results allow us to suggest that LAS should be considered in the hospital treatment of PQ poisonings. © 2008 Elsevier Ireland Ltd. All rights reserved. |
Sousa, C; Pontes, H; Carmo, H; Dinis-Oliveira, R J; Valentão, P; Andrade, P B; Remião, F; Bastos, M L; Carvalho, F Water extracts of Brassica oleracea var. costata potentiate paraquat toxicity to rat hepatocytes in vitro Journal Article 23 (6), pp. 1131-1138, 2009, (cited By 10). @article{Sousa20091131, title = {Water extracts of Brassica oleracea var. costata potentiate paraquat toxicity to rat hepatocytes in vitro}, author = {C Sousa and H Pontes and H Carmo and R J Dinis-Oliveira and P Valentão and P B Andrade and F Remião and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-68049086630&doi=10.1016%2fj.tiv.2009.05.012&partnerID=40&md5=b5f6f3e047078c8f0aaeaf8636143ab9}, doi = {10.1016/j.tiv.2009.05.012}, year = {2009}, date = {2009-01-01}, volume = {23}, number = {6}, pages = {1131-1138}, abstract = {Tronchuda cabbage extracts have been proven to have antioxidant potential against various oxidative species in cell free systems, though its antioxidant potential in cellular models remained to be demonstrated. In the present study, we used primary cultures of rat hepatocytes for the cellular assay system and paraquat PQ exposure as a pro-oxidant model agent, to test whether tronchuda cabbage hydrolysed water extracts provide protective or aggravating effects towards PQ-induced oxidative stress and cell death. For this purpose cellular parameters related to oxidative stress were measured, namely the generation of superoxide anion, glutathione oxidation, lipid peroxidation, intracellular ATP levels, activation of nuclear factor-κB (NF-κB), activity of antioxidant enzymes, and cell death. The obtained results demonstrated that the studied hydrolysed water extracts of tronchuda cabbage, especially rich in kaempferol (84%) and other polyphenols, namely hydroxycinnamic acids and traces of quercetin, can potentiate the toxicity of PQ in primary cultures of rat hepatocytes. These results highlight that prospective antioxidant effects of plant extracts, observed in vitro, using non-cellular systems, are not always confirmed in cellular models, in which the concentrations required to scavenge pro-oxidant species may be highly detrimental to the cells. © 2009 Elsevier Ltd. All rights reserved.}, note = {cited By 10}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tronchuda cabbage extracts have been proven to have antioxidant potential against various oxidative species in cell free systems, though its antioxidant potential in cellular models remained to be demonstrated. In the present study, we used primary cultures of rat hepatocytes for the cellular assay system and paraquat PQ exposure as a pro-oxidant model agent, to test whether tronchuda cabbage hydrolysed water extracts provide protective or aggravating effects towards PQ-induced oxidative stress and cell death. For this purpose cellular parameters related to oxidative stress were measured, namely the generation of superoxide anion, glutathione oxidation, lipid peroxidation, intracellular ATP levels, activation of nuclear factor-κB (NF-κB), activity of antioxidant enzymes, and cell death. The obtained results demonstrated that the studied hydrolysed water extracts of tronchuda cabbage, especially rich in kaempferol (84%) and other polyphenols, namely hydroxycinnamic acids and traces of quercetin, can potentiate the toxicity of PQ in primary cultures of rat hepatocytes. These results highlight that prospective antioxidant effects of plant extracts, observed in vitro, using non-cellular systems, are not always confirmed in cellular models, in which the concentrations required to scavenge pro-oxidant species may be highly detrimental to the cells. © 2009 Elsevier Ltd. All rights reserved. |
Dinis-Oliveira, R J; de Pinho, P G; Santos, L; Teixeira, H; Magalhães, T; Santos, A; de Bastos, M L; Remião, F; Duarte, J A; Carvalho, F 4 (9), 2009, (cited By 41). @article{Dinis-Oliveira2009b, title = {Postmortem analyses unveil the poor efficacy of decontamination, anti-inflammatory and immunosuppressive therapies in paraquat human intoxications}, author = {R J Dinis-Oliveira and P G de Pinho and L Santos and H Teixeira and T Magalhães and A Santos and M L de Bastos and F Remião and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-70349653257&doi=10.1371%2fjournal.pone.0007149&partnerID=40&md5=31b3b187b69ea3040215d6191885675c}, doi = {10.1371/journal.pone.0007149}, year = {2009}, date = {2009-01-01}, volume = {4}, number = {9}, abstract = {Background: Fatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study. Methodology/Principal Findings: For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NFκB) activation and excessive collagen deposition. Conclusions/Significance: Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process. © 2009 Dinis-Oliveria et al.}, note = {cited By 41}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Fatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study. Methodology/Principal Findings: For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NFκB) activation and excessive collagen deposition. Conclusions/Significance: Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process. © 2009 Dinis-Oliveria et al. |
Dinis-Oliveira, R J; Magalhães, T; Carvalho, F; Santos, A A cocaine body packer case report: Clinical and forensic aspects Journal Article 47 (6), pp. 590-591, 2009, (cited By 9). @article{Dinis-Oliveira2009590, title = {A cocaine body packer case report: Clinical and forensic aspects}, author = {R J Dinis-Oliveira and T Magalhães and F Carvalho and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-67651146921&doi=10.1080%2f15563650902956423&partnerID=40&md5=c7e1a075c1d74d8aa92145c9ece70c29}, doi = {10.1080/15563650902956423}, year = {2009}, date = {2009-01-01}, volume = {47}, number = {6}, pages = {590-591}, note = {cited By 9}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dinis-Oliveira, R J; Magalhães, T; Carvalho, F; Santos, A A cocaine body packer case report: Clinical and forensic aspects Journal Article Clinical Toxicology, 47 (6), pp. 590-591, 2009, (cited By 10). @article{Dinis-Oliveira2009590b, title = {A cocaine body packer case report: Clinical and forensic aspects}, author = {R J Dinis-Oliveira and T Magalhães and F Carvalho and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-67651146921&doi=10.1080%2f15563650902956423&partnerID=40&md5=c7e1a075c1d74d8aa92145c9ece70c29}, doi = {10.1080/15563650902956423}, year = {2009}, date = {2009-01-01}, journal = {Clinical Toxicology}, volume = {47}, number = {6}, pages = {590-591}, note = {cited By 10}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dinis-Oliveira, R J; de Pinho, P G; Santos, L; Teixeira, H; Magalhães, T; Santos, A; de Bastos, M L; Remião, F; Duarte, J A; Carvalho, F PLoS ONE, 4 (9), 2009, (cited By 45). @article{Dinis-Oliveira2009e, title = {Postmortem analyses unveil the poor efficacy of decontamination, anti-inflammatory and immunosuppressive therapies in paraquat human intoxications}, author = {R J Dinis-Oliveira and P G de Pinho and L Santos and H Teixeira and T Magalhães and A Santos and M L de Bastos and F Remião and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-70349653257&doi=10.1371%2fjournal.pone.0007149&partnerID=40&md5=31b3b187b69ea3040215d6191885675c}, doi = {10.1371/journal.pone.0007149}, year = {2009}, date = {2009-01-01}, journal = {PLoS ONE}, volume = {4}, number = {9}, abstract = {Background: Fatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study. Methodology/Principal Findings: For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NFκB) activation and excessive collagen deposition. Conclusions/Significance: Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process. © 2009 Dinis-Oliveria et al.}, note = {cited By 45}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Fatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study. Methodology/Principal Findings: For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NFκB) activation and excessive collagen deposition. Conclusions/Significance: Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process. © 2009 Dinis-Oliveria et al. |
Sousa, C; Pontes, H; Carmo, H; Dinis-Oliveira, R J; Valentão, P; Andrade, P B; Remião, F; Bastos, M L; Carvalho, F Water extracts of Brassica oleracea var. costata potentiate paraquat toxicity to rat hepatocytes in vitro Journal Article Toxicology in Vitro, 23 (6), pp. 1131-1138, 2009, (cited By 11). @article{Sousa20091131b, title = {Water extracts of Brassica oleracea var. costata potentiate paraquat toxicity to rat hepatocytes in vitro}, author = {C Sousa and H Pontes and H Carmo and R J Dinis-Oliveira and P Valentão and P B Andrade and F Remião and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-68049086630&doi=10.1016%2fj.tiv.2009.05.012&partnerID=40&md5=b5f6f3e047078c8f0aaeaf8636143ab9}, doi = {10.1016/j.tiv.2009.05.012}, year = {2009}, date = {2009-01-01}, journal = {Toxicology in Vitro}, volume = {23}, number = {6}, pages = {1131-1138}, abstract = {Tronchuda cabbage extracts have been proven to have antioxidant potential against various oxidative species in cell free systems, though its antioxidant potential in cellular models remained to be demonstrated. In the present study, we used primary cultures of rat hepatocytes for the cellular assay system and paraquat PQ exposure as a pro-oxidant model agent, to test whether tronchuda cabbage hydrolysed water extracts provide protective or aggravating effects towards PQ-induced oxidative stress and cell death. For this purpose cellular parameters related to oxidative stress were measured, namely the generation of superoxide anion, glutathione oxidation, lipid peroxidation, intracellular ATP levels, activation of nuclear factor-κB (NF-κB), activity of antioxidant enzymes, and cell death. The obtained results demonstrated that the studied hydrolysed water extracts of tronchuda cabbage, especially rich in kaempferol (84%) and other polyphenols, namely hydroxycinnamic acids and traces of quercetin, can potentiate the toxicity of PQ in primary cultures of rat hepatocytes. These results highlight that prospective antioxidant effects of plant extracts, observed in vitro, using non-cellular systems, are not always confirmed in cellular models, in which the concentrations required to scavenge pro-oxidant species may be highly detrimental to the cells. © 2009 Elsevier Ltd. All rights reserved.}, note = {cited By 11}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tronchuda cabbage extracts have been proven to have antioxidant potential against various oxidative species in cell free systems, though its antioxidant potential in cellular models remained to be demonstrated. In the present study, we used primary cultures of rat hepatocytes for the cellular assay system and paraquat PQ exposure as a pro-oxidant model agent, to test whether tronchuda cabbage hydrolysed water extracts provide protective or aggravating effects towards PQ-induced oxidative stress and cell death. For this purpose cellular parameters related to oxidative stress were measured, namely the generation of superoxide anion, glutathione oxidation, lipid peroxidation, intracellular ATP levels, activation of nuclear factor-κB (NF-κB), activity of antioxidant enzymes, and cell death. The obtained results demonstrated that the studied hydrolysed water extracts of tronchuda cabbage, especially rich in kaempferol (84%) and other polyphenols, namely hydroxycinnamic acids and traces of quercetin, can potentiate the toxicity of PQ in primary cultures of rat hepatocytes. These results highlight that prospective antioxidant effects of plant extracts, observed in vitro, using non-cellular systems, are not always confirmed in cellular models, in which the concentrations required to scavenge pro-oxidant species may be highly detrimental to the cells. © 2009 Elsevier Ltd. All rights reserved. |
Dinis-Oliveira, R J; Pontes, H; Bastos, M L; Remião, F; Duarte, J A; Carvalho, F An effective antidote for paraquat poisonings: The treatment with lysine acetylsalicylate Journal Article Toxicology, 255 (3), pp. 187-193, 2009, (cited By 39). @article{Dinis-Oliveira2009187b, title = {An effective antidote for paraquat poisonings: The treatment with lysine acetylsalicylate}, author = {R J Dinis-Oliveira and H Pontes and M L Bastos and F Remião and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-58149157786&doi=10.1016%2fj.tox.2008.10.015&partnerID=40&md5=0a47a85733fc009f2d108a5d54a08a69}, doi = {10.1016/j.tox.2008.10.015}, year = {2009}, date = {2009-01-01}, journal = {Toxicology}, volume = {255}, number = {3}, pages = {187-193}, abstract = {Sodium salicylate (NaSAL) has been shown to have a multifactorial protection mechanism against paraquat (PQ)-induced toxicity, due to its ability to modulate inflammatory signalling systems, to prevent oxidative stress and to its capacity to chelate PQ. Considering that currently there is no pharmaceutical formulation available for parenteral administration of NaSAL, the aim of the present study was to evaluate the antidotal feasibility of a salicylate prodrug, lysine acetylsalicylate (LAS), accessible for parenteral administrations. PQ was administered to Wistar rats by gavage (125 mg/kg of PQ ion) and the treatment was performed intraperitoneally with different doses (100, 200 and 400 mg/kg of body weight) of LAS. Survival rate was followed during 30 days and living animals at this endpoint were sacrificed for lung, kidney, liver, jejune and heart histological analysis. It was shown, that the salicylate prodrug, LAS, available in a large number of hospitals, is also effective in the treatment of PQ intoxications. From all tested LAS doses, 200 mg/kg assured animal's full survival. Comparatively to 60% of mortality observed in PQ only exposed animals, the lethality was higher (80%) in the group that received 400 mg/kg of LAS 2 h after PQ administration. The dose of 100 mg/kg of LAS showed only a modest protection (60% of survival). Collagen deposition was observed by histological analysis in survived animals of all experimental groups, being less pronounced in animals receiving 200 mg/kg of LAS, reinforcing the importance of this dose against tissue damage induced by PQ. The results allow us to suggest that LAS should be considered in the hospital treatment of PQ poisonings. © 2008 Elsevier Ireland Ltd. All rights reserved.}, note = {cited By 39}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sodium salicylate (NaSAL) has been shown to have a multifactorial protection mechanism against paraquat (PQ)-induced toxicity, due to its ability to modulate inflammatory signalling systems, to prevent oxidative stress and to its capacity to chelate PQ. Considering that currently there is no pharmaceutical formulation available for parenteral administration of NaSAL, the aim of the present study was to evaluate the antidotal feasibility of a salicylate prodrug, lysine acetylsalicylate (LAS), accessible for parenteral administrations. PQ was administered to Wistar rats by gavage (125 mg/kg of PQ ion) and the treatment was performed intraperitoneally with different doses (100, 200 and 400 mg/kg of body weight) of LAS. Survival rate was followed during 30 days and living animals at this endpoint were sacrificed for lung, kidney, liver, jejune and heart histological analysis. It was shown, that the salicylate prodrug, LAS, available in a large number of hospitals, is also effective in the treatment of PQ intoxications. From all tested LAS doses, 200 mg/kg assured animal's full survival. Comparatively to 60% of mortality observed in PQ only exposed animals, the lethality was higher (80%) in the group that received 400 mg/kg of LAS 2 h after PQ administration. The dose of 100 mg/kg of LAS showed only a modest protection (60% of survival). Collagen deposition was observed by histological analysis in survived animals of all experimental groups, being less pronounced in animals receiving 200 mg/kg of LAS, reinforcing the importance of this dose against tissue damage induced by PQ. The results allow us to suggest that LAS should be considered in the hospital treatment of PQ poisonings. © 2008 Elsevier Ireland Ltd. All rights reserved. |
2008 |
Dinis-Oliveira, R J; Duarte, J A; Sánchez-Navarro, A; Remião, F; Bastos, M L; Carvalho, F Paraquat poisonings: Mechanisms of lung toxicity, clinical features, and treatment Journal Article 38 (1), pp. 13-71, 2008, (cited By 310). @article{Dinis-Oliveira200813, title = {Paraquat poisonings: Mechanisms of lung toxicity, clinical features, and treatment}, author = {R J Dinis-Oliveira and J A Duarte and A Sánchez-Navarro and F Remião and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-37549016807&doi=10.1080%2f10408440701669959&partnerID=40&md5=5e8ce6285117f02d9b62769f66248b02}, doi = {10.1080/10408440701669959}, year = {2008}, date = {2008-01-01}, volume = {38}, number = {1}, pages = {13-71}, abstract = {Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies. Copyright © 2008 Informa Healthcare USA, Inc.}, note = {cited By 310}, keywords = {}, pubstate = {published}, tppubtype = {article} } Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies. Copyright © 2008 Informa Healthcare USA, Inc. |
Valle, De Jesús M J; Dinis-Oliveira, R J; Carvalho, F; Bastos, M L; Navarro, A S Toxicological evaluation of lactose and chitosan delivered by inhalation Journal Article 19 (3), pp. 387-397, 2008, (cited By 9). @article{DeJesúsValle2008387, title = {Toxicological evaluation of lactose and chitosan delivered by inhalation}, author = {M J De Jesús Valle and R J Dinis-Oliveira and F Carvalho and M L Bastos and A S Navarro}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-39749105239&doi=10.1163%2f156856208783721038&partnerID=40&md5=832b6ac5117d4b30201def831cb3d1df}, doi = {10.1163/156856208783721038}, year = {2008}, date = {2008-01-01}, volume = {19}, number = {3}, pages = {387-397}, abstract = {These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione (GSSG), myeloperoxidase (MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 ± 2.27 versus 15.10 ± 7.27 (P = 0.011) for MPO and 0.89 ± 0.68 versus 2.02 ± 0.22 (P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators. © Koninklijke Brill NV, 2008.}, note = {cited By 9}, keywords = {}, pubstate = {published}, tppubtype = {article} } These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione (GSSG), myeloperoxidase (MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 ± 2.27 versus 15.10 ± 7.27 (P = 0.011) for MPO and 0.89 ± 0.68 versus 2.02 ± 0.22 (P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators. © Koninklijke Brill NV, 2008. |
Dinis-Oliveira, R J; de Pinho, P G; Ferreira, A C S; Silva, A M S; Afonso, C; d Bastos, M L; Remião, F; Duarte, J A; Carvalho, F Reactivity of paraquat with sodium salicylate: Formation of stable complexes Journal Article 249 (2-3), pp. 130-139, 2008, (cited By 14). @article{Dinis-Oliveira2008130, title = {Reactivity of paraquat with sodium salicylate: Formation of stable complexes}, author = {R J Dinis-Oliveira and P G de Pinho and A C S Ferreira and A M S Silva and C Afonso and M d L Bastos and F Remião and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-46449127649&doi=10.1016%2fj.tox.2008.04.014&partnerID=40&md5=1d6461f2369d39d26bf76fe5712e4b47}, doi = {10.1016/j.tox.2008.04.014}, year = {2008}, date = {2008-01-01}, volume = {249}, number = {2-3}, pages = {130-139}, abstract = {Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the anti-thrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2-3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the charge-transfer complexes with m/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ. © 2008 Elsevier Ireland Ltd. All rights reserved.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the anti-thrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2-3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the charge-transfer complexes with m/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ. © 2008 Elsevier Ireland Ltd. All rights reserved. |
Pontes, H; Duarte, J A; de Pinho, P G; Soares, M E; Fernandes, E; Dinis-Oliveira, R J; Sousa, C; Silva, R; Carmo, H; Casal, S; Remião, F; Carvalho, F; Bastos, M L Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice Journal Article 252 (1-3), pp. 64-71, 2008, (cited By 31). @article{Pontes200864, title = {Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice}, author = {H Pontes and J A Duarte and P G de Pinho and M E Soares and E Fernandes and R J Dinis-Oliveira and C Sousa and R Silva and H Carmo and S Casal and F Remião and F Carvalho and M L Bastos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-53249117160&doi=10.1016%2fj.tox.2008.07.064&partnerID=40&md5=aa79b7b7900f0afee814e5fce367073a}, doi = {10.1016/j.tox.2008.07.064}, year = {2008}, date = {2008-01-01}, volume = {252}, number = {1-3}, pages = {64-71}, abstract = {3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative drug with entactogenic, empathogenic and hallucinogenic properties, commonly consumed at rave parties in a polydrug abuse pattern, especially with cannabis, tobacco and ethanol. Since both MDMA and ethanol may cause deleterious effects to the liver, the evaluation of their putative hepatotoxic interaction is of great interest, especially considering that most of the MDMA users are regular ethanol consumers. Thus, the aim of the present study was to evaluate, in vivo, the acute hepatotoxic effects of MDMA (10 mg/kg i.p.) in CD-1 mice previously exposed to 12% ethanol as drinking fluid (for 8 weeks). Body temperature was continuously measured for 12 h after MDMA administration and, after 24 h, hepatic damage was evaluated. The administration of MDMA to non pre-treated mice resulted in sustained hyperthermia, which was significantly increased in ethanol pre-exposed mice. A correspondent higher increase of hepatic heat shock transcription factor (HSF-1) activation was also observed in the latter group. Furthermore, MDMA administration resulted in liver damage as confirmed by histological analysis, slight decrease in liver weight and increased plasma transaminases levels. These hepatotoxic effects were also exacerbated when mice were pre-treated with ethanol. The activities of some antioxidant enzymes (such as SOD, GPx and Catalase) were modified by ethanol, MDMA and their joint action. The hepatotoxicity resulting from the simultaneous exposure to MDMA and ethanol was associated with a higher activation of NF-κB, indicating a pro-inflammatory effect in this organ. In conclusion, the obtained results strongly suggest that the consumption of ethanol increases the hyperthermic and hepatotoxic effects associated with MDMA abuse. © 2008 Elsevier Ireland Ltd. All rights reserved.}, note = {cited By 31}, keywords = {}, pubstate = {published}, tppubtype = {article} } 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative drug with entactogenic, empathogenic and hallucinogenic properties, commonly consumed at rave parties in a polydrug abuse pattern, especially with cannabis, tobacco and ethanol. Since both MDMA and ethanol may cause deleterious effects to the liver, the evaluation of their putative hepatotoxic interaction is of great interest, especially considering that most of the MDMA users are regular ethanol consumers. Thus, the aim of the present study was to evaluate, in vivo, the acute hepatotoxic effects of MDMA (10 mg/kg i.p.) in CD-1 mice previously exposed to 12% ethanol as drinking fluid (for 8 weeks). Body temperature was continuously measured for 12 h after MDMA administration and, after 24 h, hepatic damage was evaluated. The administration of MDMA to non pre-treated mice resulted in sustained hyperthermia, which was significantly increased in ethanol pre-exposed mice. A correspondent higher increase of hepatic heat shock transcription factor (HSF-1) activation was also observed in the latter group. Furthermore, MDMA administration resulted in liver damage as confirmed by histological analysis, slight decrease in liver weight and increased plasma transaminases levels. These hepatotoxic effects were also exacerbated when mice were pre-treated with ethanol. The activities of some antioxidant enzymes (such as SOD, GPx and Catalase) were modified by ethanol, MDMA and their joint action. The hepatotoxicity resulting from the simultaneous exposure to MDMA and ethanol was associated with a higher activation of NF-κB, indicating a pro-inflammatory effect in this organ. In conclusion, the obtained results strongly suggest that the consumption of ethanol increases the hyperthermic and hepatotoxic effects associated with MDMA abuse. © 2008 Elsevier Ireland Ltd. All rights reserved. |
Pontes, H; Duarte, J A; de Pinho, P G; Soares, M E; Fernandes, E; Dinis-Oliveira, R J; Sousa, C; Silva, R; Carmo, H; Casal, S; Remião, F; Carvalho, F; Bastos, M L Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice Journal Article Toxicology, 252 (1-3), pp. 64-71, 2008, (cited By 33). @article{Pontes200864b, title = {Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice}, author = {H Pontes and J A Duarte and P G de Pinho and M E Soares and E Fernandes and R J Dinis-Oliveira and C Sousa and R Silva and H Carmo and S Casal and F Remião and F Carvalho and M L Bastos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-53249117160&doi=10.1016%2fj.tox.2008.07.064&partnerID=40&md5=aa79b7b7900f0afee814e5fce367073a}, doi = {10.1016/j.tox.2008.07.064}, year = {2008}, date = {2008-01-01}, journal = {Toxicology}, volume = {252}, number = {1-3}, pages = {64-71}, abstract = {3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative drug with entactogenic, empathogenic and hallucinogenic properties, commonly consumed at rave parties in a polydrug abuse pattern, especially with cannabis, tobacco and ethanol. Since both MDMA and ethanol may cause deleterious effects to the liver, the evaluation of their putative hepatotoxic interaction is of great interest, especially considering that most of the MDMA users are regular ethanol consumers. Thus, the aim of the present study was to evaluate, in vivo, the acute hepatotoxic effects of MDMA (10 mg/kg i.p.) in CD-1 mice previously exposed to 12% ethanol as drinking fluid (for 8 weeks). Body temperature was continuously measured for 12 h after MDMA administration and, after 24 h, hepatic damage was evaluated. The administration of MDMA to non pre-treated mice resulted in sustained hyperthermia, which was significantly increased in ethanol pre-exposed mice. A correspondent higher increase of hepatic heat shock transcription factor (HSF-1) activation was also observed in the latter group. Furthermore, MDMA administration resulted in liver damage as confirmed by histological analysis, slight decrease in liver weight and increased plasma transaminases levels. These hepatotoxic effects were also exacerbated when mice were pre-treated with ethanol. The activities of some antioxidant enzymes (such as SOD, GPx and Catalase) were modified by ethanol, MDMA and their joint action. The hepatotoxicity resulting from the simultaneous exposure to MDMA and ethanol was associated with a higher activation of NF-κB, indicating a pro-inflammatory effect in this organ. In conclusion, the obtained results strongly suggest that the consumption of ethanol increases the hyperthermic and hepatotoxic effects associated with MDMA abuse. © 2008 Elsevier Ireland Ltd. All rights reserved.}, note = {cited By 33}, keywords = {}, pubstate = {published}, tppubtype = {article} } 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative drug with entactogenic, empathogenic and hallucinogenic properties, commonly consumed at rave parties in a polydrug abuse pattern, especially with cannabis, tobacco and ethanol. Since both MDMA and ethanol may cause deleterious effects to the liver, the evaluation of their putative hepatotoxic interaction is of great interest, especially considering that most of the MDMA users are regular ethanol consumers. Thus, the aim of the present study was to evaluate, in vivo, the acute hepatotoxic effects of MDMA (10 mg/kg i.p.) in CD-1 mice previously exposed to 12% ethanol as drinking fluid (for 8 weeks). Body temperature was continuously measured for 12 h after MDMA administration and, after 24 h, hepatic damage was evaluated. The administration of MDMA to non pre-treated mice resulted in sustained hyperthermia, which was significantly increased in ethanol pre-exposed mice. A correspondent higher increase of hepatic heat shock transcription factor (HSF-1) activation was also observed in the latter group. Furthermore, MDMA administration resulted in liver damage as confirmed by histological analysis, slight decrease in liver weight and increased plasma transaminases levels. These hepatotoxic effects were also exacerbated when mice were pre-treated with ethanol. The activities of some antioxidant enzymes (such as SOD, GPx and Catalase) were modified by ethanol, MDMA and their joint action. The hepatotoxicity resulting from the simultaneous exposure to MDMA and ethanol was associated with a higher activation of NF-κB, indicating a pro-inflammatory effect in this organ. In conclusion, the obtained results strongly suggest that the consumption of ethanol increases the hyperthermic and hepatotoxic effects associated with MDMA abuse. © 2008 Elsevier Ireland Ltd. All rights reserved. |
Dinis-Oliveira, R J; de Pinho, P G; Ferreira, A C S; Silva, A M S; Afonso, C; d Bastos, M L; Remião, F; Duarte, J A; Carvalho, F Reactivity of paraquat with sodium salicylate: Formation of stable complexes Journal Article Toxicology, 249 (2-3), pp. 130-139, 2008, (cited By 17). @article{Dinis-Oliveira2008130b, title = {Reactivity of paraquat with sodium salicylate: Formation of stable complexes}, author = {R J Dinis-Oliveira and P G de Pinho and A C S Ferreira and A M S Silva and C Afonso and M d L Bastos and F Remião and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-46449127649&doi=10.1016%2fj.tox.2008.04.014&partnerID=40&md5=1d6461f2369d39d26bf76fe5712e4b47}, doi = {10.1016/j.tox.2008.04.014}, year = {2008}, date = {2008-01-01}, journal = {Toxicology}, volume = {249}, number = {2-3}, pages = {130-139}, abstract = {Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the anti-thrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2-3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the charge-transfer complexes with m/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ. © 2008 Elsevier Ireland Ltd. All rights reserved.}, note = {cited By 17}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sodium salicylate (NaSAL) has been shown to be a promising antidote for the treatment of paraquat (PQ) poisonings. The modulation of the pro-oxidant and pro-inflammatory pathways, as well as the anti-thrombogenic properties of NaSAL are probably essential features for the healing effects provided by this drug. Nevertheless, a possible direct chemical reactivity between PQ and NaSAL is also a putative pathway to be considered, this hypothesis being the ground of the present study. In accordance, it is shown, for the first time that PQ and NaSAL react immediately in aqueous medium and within 2-3 min in the solid state. Photographs and scanning electron photomicrographs indicated that a new chemical entity is formed when both compounds are mixed. This assumption was corroborated by the evaluation of the melting point, and through several analytical techniques, namely ultraviolet/visible spectroscopy, nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS), liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) and infrared spectroscopy, which revealed that stable charge-transfer complexes are formed when PQ is mixed with NaSAL. LC/ESI/MS/MS allowed obtaining the stoichiometry of the charge-transfer complexes. In order to increase resolution, single value decomposition, acting as a filter, showed that the charge-transfer complexes with m/z 483, 643 and 803 correspond to the pseudo-molecular ions, respectively 1:2, 1:3 and 1:4 (PQ:NaSAL). In conclusion, these results provided a new and important mechanism of action of NaSAL against the toxicity mediated by PQ. © 2008 Elsevier Ireland Ltd. All rights reserved. |
Valle, De Jesús M J; Dinis-Oliveira, R J; Carvalho, F; Bastos, M L; Navarro, A S Toxicological evaluation of lactose and chitosan delivered by inhalation Journal Article Journal of Biomaterials Science, Polymer Edition, 19 (3), pp. 387-397, 2008, (cited By 12). @article{DeJesúsValle2008387b, title = {Toxicological evaluation of lactose and chitosan delivered by inhalation}, author = {M J De Jesús Valle and R J Dinis-Oliveira and F Carvalho and M L Bastos and A S Navarro}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-39749105239&doi=10.1163%2f156856208783721038&partnerID=40&md5=832b6ac5117d4b30201def831cb3d1df}, doi = {10.1163/156856208783721038}, year = {2008}, date = {2008-01-01}, journal = {Journal of Biomaterials Science, Polymer Edition}, volume = {19}, number = {3}, pages = {387-397}, abstract = {These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione (GSSG), myeloperoxidase (MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 ± 2.27 versus 15.10 ± 7.27 (P = 0.011) for MPO and 0.89 ± 0.68 versus 2.02 ± 0.22 (P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators. © Koninklijke Brill NV, 2008.}, note = {cited By 12}, keywords = {}, pubstate = {published}, tppubtype = {article} } These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione (GSSG), myeloperoxidase (MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 ± 2.27 versus 15.10 ± 7.27 (P = 0.011) for MPO and 0.89 ± 0.68 versus 2.02 ± 0.22 (P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators. © Koninklijke Brill NV, 2008. |
Dinis-Oliveira, R J; Duarte, J A; Sánchez-Navarro, A; Remião, F; Bastos, M L; Carvalho, F Paraquat poisonings: Mechanisms of lung toxicity, clinical features, and treatment Journal Article Critical Reviews in Toxicology, 38 (1), pp. 13-71, 2008, (cited By 370). @article{Dinis-Oliveira200813d, title = {Paraquat poisonings: Mechanisms of lung toxicity, clinical features, and treatment}, author = {R J Dinis-Oliveira and J A Duarte and A Sánchez-Navarro and F Remião and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-37549016807&doi=10.1080%2f10408440701669959&partnerID=40&md5=5e8ce6285117f02d9b62769f66248b02}, doi = {10.1080/10408440701669959}, year = {2008}, date = {2008-01-01}, journal = {Critical Reviews in Toxicology}, volume = {38}, number = {1}, pages = {13-71}, abstract = {Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies. Copyright © 2008 Informa Healthcare USA, Inc.}, note = {cited By 370}, keywords = {}, pubstate = {published}, tppubtype = {article} } Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies. Copyright © 2008 Informa Healthcare USA, Inc. |
2007 |
Dinis-Oliveira, R J; Sousa, C; Remião, F; Duarte, J A; Navarro, A S; Bastos, M L; Carvalho, F Full survival of paraquat-exposed rats after treatment with sodium salicylate Journal Article Free Radical Biology and Medicine, 42 (7), pp. 1017-1028, 2007, (cited By 71). @article{Dinis-Oliveira20071017b, title = {Full survival of paraquat-exposed rats after treatment with sodium salicylate}, author = {R J Dinis-Oliveira and C Sousa and F Remião and J A Duarte and A S Navarro and M L Bastos and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33847611966&doi=10.1016%2fj.freeradbiomed.2006.12.031&partnerID=40&md5=899e3c5c6723776b930e5f6357b47493}, doi = {10.1016/j.freeradbiomed.2006.12.031}, year = {2007}, date = {2007-01-01}, journal = {Free Radical Biology and Medicine}, volume = {42}, number = {7}, pages = {1017-1028}, abstract = {Over the past decades, there have been numerous fatalities resulting from accidental or voluntary ingestion of the widely used herbicide paraquat dichloride (methyl viologen; PQ). Considering that the main target organ for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, inflammation, disseminated intravascular coagulation, and activation of transcriptional regulatory mechanisms, it may be hypothesized that an antidote against PQ poisonings should counteract all these effects. For this purpose, sodium salicylate (NaSAL) may constitute an adequate therapeutic drug, due to its ability to modulate inflammatory signaling systems and to prevent oxidative stress. To test this hypothesis, NaSAL (200 mg/kg ip) was injected in rats 2 h after exposure to a toxic dose of PQ (25 mg/kg, ip). NaSAL treatment caused a significant reduction in PQ-induced oxidative stress, platelet activation, and nuclear factor (NF)-κB activation in lung. In addition, histopathological lesions induced by PQ in lung were strongly attenuated and the oxidant-induced increases of glutathione peroxidase and catalase expression became absent. These effects were associated with a full survival of the PQ-treated rats (extended for more than 30 days) in comparison with 100% of mortality by Day 6 in animals exposed only to PQ, suggesting that NaSAL constitutes an important and valuable therapeutic drug to be used against PQ-induced toxicity. Indeed, NaSAL constitutes the first compound with such degree of success (100% survival). © 2007 Elsevier Inc. All rights reserved.}, note = {cited By 71}, keywords = {}, pubstate = {published}, tppubtype = {article} } Over the past decades, there have been numerous fatalities resulting from accidental or voluntary ingestion of the widely used herbicide paraquat dichloride (methyl viologen; PQ). Considering that the main target organ for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, inflammation, disseminated intravascular coagulation, and activation of transcriptional regulatory mechanisms, it may be hypothesized that an antidote against PQ poisonings should counteract all these effects. For this purpose, sodium salicylate (NaSAL) may constitute an adequate therapeutic drug, due to its ability to modulate inflammatory signaling systems and to prevent oxidative stress. To test this hypothesis, NaSAL (200 mg/kg ip) was injected in rats 2 h after exposure to a toxic dose of PQ (25 mg/kg, ip). NaSAL treatment caused a significant reduction in PQ-induced oxidative stress, platelet activation, and nuclear factor (NF)-κB activation in lung. In addition, histopathological lesions induced by PQ in lung were strongly attenuated and the oxidant-induced increases of glutathione peroxidase and catalase expression became absent. These effects were associated with a full survival of the PQ-treated rats (extended for more than 30 days) in comparison with 100% of mortality by Day 6 in animals exposed only to PQ, suggesting that NaSAL constitutes an important and valuable therapeutic drug to be used against PQ-induced toxicity. Indeed, NaSAL constitutes the first compound with such degree of success (100% survival). © 2007 Elsevier Inc. All rights reserved. |
Ricardo Dinis-Oliveira
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