2014 |
Lima, Costa S A; Silvestre, R; Barros, D; Cunha, J; Baltazar, M T; Dinis-Oliveira, R J; Cordeiro-da-Silva, A Crucial CD8+ T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis Journal Article 10 (5), pp. 1021-1030, 2014, (cited By 8). @article{CostaLima20141021, title = {Crucial CD8+ T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis}, author = {S A Costa Lima and R Silvestre and D Barros and J Cunha and M T Baltazar and R J Dinis-Oliveira and A Cordeiro-da-Silva}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84903548865&doi=10.1016%2fj.nano.2013.12.013&partnerID=40&md5=dcf1567c028df308141bff21ed775d1b}, doi = {10.1016/j.nano.2013.12.013}, year = {2014}, date = {2014-01-01}, volume = {10}, number = {5}, pages = {1021-1030}, abstract = {This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was >90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8+- but not CD4+-T lymphocytes. Overall, we demonstrate a crucial role for CD8+ cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. From the Clinical Editor: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy. © 2014 Elsevier Inc.}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was >90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8+- but not CD4+-T lymphocytes. Overall, we demonstrate a crucial role for CD8+ cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. From the Clinical Editor: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy. © 2014 Elsevier Inc. |
Baltazar, M T; Dinis-Oliveira, R J; Martins, A; Bastos, M D L; Duarte, J A; Guilhermino, L; Carvalho, F 146 , pp. 137-143, 2014, (cited By 7). @article{Baltazar2014137, title = {Lysine acetylsalicylate increases the safety of a paraquat formulation to freshwater primary producers: A case study with the microalga chlorella vulgaris}, author = {M T Baltazar and R J Dinis-Oliveira and A Martins and M D L Bastos and J A Duarte and L Guilhermino and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84888784605&doi=10.1016%2fj.aquatox.2013.10.034&partnerID=40&md5=59d6b13937c7c7c997d5c773592227e8}, doi = {10.1016/j.aquatox.2013.10.034}, year = {2014}, date = {2014-01-01}, volume = {146}, pages = {137-143}, abstract = {Large amounts of herbicides are presently used in the industrialized nations worldwide, with an inexorable burden to the environment, especially to aquatic ecosystems. Primary producers such as microalgae are of especial concern because they are vital for the input of energy into the ecosystem and for the maintenance of oxygen in water on which most of other marine life forms depend on. The herbicide paraquat (PQ) is known to cause inhibition of photosynthesis and irreversible damage to photosynthetic organisms through generation of reactive oxygen species in a light-dependent manner. Previous studies have led to the development of a new formulation of PQ containing lysine acetylsalicylate (LAS) as an antidote, which was shown to prevent the mammalian toxicity of PQ, while maintaining the herbicidal effect. However, the safety of this formulation to primary producers in relation to commercially available PQ formulations has hitherto not been established. Therefore, the aim of this study was to evaluate the toxicity of the PQ+LAS formulation in comparison with the PQ, using Chlorella vulgaris as a test organism. Effect criterion was the inhibition of microalgal population growth. Following a 96h exposure to increasing concentrations of PQ, C. vulgaris growth was almost completely inhibited, an effect that was significantly prevented by LAS at the proportion used in the formulation (PQ+LAS) 1:2 (mol/mol), while the highest protection was achieved at the proportion of 1:8. In conclusion, the present work demonstrated that the new formulation with PQ+LAS has a reduced toxicity to C. vulgaris when compared to Gramoxone®. © 2013 Elsevier B.V.}, note = {cited By 7}, keywords = {}, pubstate = {published}, tppubtype = {article} } Large amounts of herbicides are presently used in the industrialized nations worldwide, with an inexorable burden to the environment, especially to aquatic ecosystems. Primary producers such as microalgae are of especial concern because they are vital for the input of energy into the ecosystem and for the maintenance of oxygen in water on which most of other marine life forms depend on. The herbicide paraquat (PQ) is known to cause inhibition of photosynthesis and irreversible damage to photosynthetic organisms through generation of reactive oxygen species in a light-dependent manner. Previous studies have led to the development of a new formulation of PQ containing lysine acetylsalicylate (LAS) as an antidote, which was shown to prevent the mammalian toxicity of PQ, while maintaining the herbicidal effect. However, the safety of this formulation to primary producers in relation to commercially available PQ formulations has hitherto not been established. Therefore, the aim of this study was to evaluate the toxicity of the PQ+LAS formulation in comparison with the PQ, using Chlorella vulgaris as a test organism. Effect criterion was the inhibition of microalgal population growth. Following a 96h exposure to increasing concentrations of PQ, C. vulgaris growth was almost completely inhibited, an effect that was significantly prevented by LAS at the proportion used in the formulation (PQ+LAS) 1:2 (mol/mol), while the highest protection was achieved at the proportion of 1:8. In conclusion, the present work demonstrated that the new formulation with PQ+LAS has a reduced toxicity to C. vulgaris when compared to Gramoxone®. © 2013 Elsevier B.V. |
Oliveira, A; Dinis-Oliveira, R J; Nogueira, A; Gonçalves, F; Silva, P; Vieira, C; Silvestre, R; Carvalho, F; Medeiros, R Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception Journal Article 47 (13-14), pp. 1209-1213, 2014, (cited By 1). @article{Oliveira20141209, title = {Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception}, author = {A Oliveira and R J Dinis-Oliveira and A Nogueira and F Gonçalves and P Silva and C Vieira and R Silvestre and F Carvalho and R Medeiros}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84899467319&doi=10.1016%2fj.clinbiochem.2014.04.009&partnerID=40&md5=a829b03e949cc6fc1af4f7e12f321824}, doi = {10.1016/j.clinbiochem.2014.04.009}, year = {2014}, date = {2014-01-01}, volume = {47}, number = {13-14}, pages = {1209-1213}, abstract = {Objectives: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (. IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/. B/. RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients. Design and methods: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters. Results: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074}, note = {cited By 1}, keywords = {}, pubstate = {published}, tppubtype = {article} } Objectives: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (. IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/. B/. RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients. Design and methods: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters. Results: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074 |
Oliveira, A; Dinis-Oliveira, R J; Nogueira, A; Azevedo, A S; Gonçalves, F; Silva, P; Carvalho, F; Medeiros, R Genetic profile and cancer-related pain: A tale from two outlier cases with bone metastatic disease Journal Article 15 (4), pp. 710-712, 2014, (cited By 5). @article{Oliveira2014710, title = {Genetic profile and cancer-related pain: A tale from two outlier cases with bone metastatic disease}, author = {A Oliveira and R J Dinis-Oliveira and A Nogueira and A S Azevedo and F Gonçalves and P Silva and F Carvalho and R Medeiros}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84898041413&doi=10.1111%2fpme.12314&partnerID=40&md5=089a772eba156b162b4ed72dca9cf650}, doi = {10.1111/pme.12314}, year = {2014}, date = {2014-01-01}, volume = {15}, number = {4}, pages = {710-712}, note = {cited By 5}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Rodrigues, V; Laforge, M; Campillo-Gimenez, L; Soundaramourty, C; Correia-de-Oliveira, A; Dinis-Oliveira, R J; Ouaissi, A; Cordeiro-da-Silva, A; Silvestre, R; Estaquier, J Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques Journal Article 10 (4), 2014, (cited By 8). @article{Rodrigues2014, title = {Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques}, author = {V Rodrigues and M Laforge and L Campillo-Gimenez and C Soundaramourty and A Correia-de-Oliveira and R J Dinis-Oliveira and A Ouaissi and A Cordeiro-da-Silva and R Silvestre and J Estaquier}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84901321731&doi=10.1371%2fjournal.ppat.1004096&partnerID=40&md5=09506596c2717a281be125519487095e}, doi = {10.1371/journal.ppat.1004096}, year = {2014}, date = {2014-01-01}, volume = {10}, number = {4}, abstract = {Leishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological profiles characterized during acute and chronic phases of infection. Parasite detection in visceral compartments during the acute phase was associated with differentiation of effector memory CD4 T cells and increased levels of Th1 transcripts. At the chronic phase, parasites colonized novel lymphoid niches concomitant with increased expression of IL10. Despite the occurrence of hypergammaglobulinemia, the production of parasite-specific IgG was poor, being confined to the acute phase and positively correlated with the frequency of an activated memory splenic B cell population. We noticed the expansion of a splenic CD4 T cell population expressing CXCR5 and Bcl-6 during acute infection that was associated with the differentiation of the activated memory B cell population. Moreover, the number of splenic germinal centers peaked at one month after infection, hence paralleling the production of specific IgG. However, at chronic infection these populations contracted impacting the production of parasite-specific IgG. Our study provides new insights into the immune events taking place in a physiologically relevant host and a mechanistic basis for the inefficient humoral response during VL. © 2014 Rodrigues et al.}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } Leishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological profiles characterized during acute and chronic phases of infection. Parasite detection in visceral compartments during the acute phase was associated with differentiation of effector memory CD4 T cells and increased levels of Th1 transcripts. At the chronic phase, parasites colonized novel lymphoid niches concomitant with increased expression of IL10. Despite the occurrence of hypergammaglobulinemia, the production of parasite-specific IgG was poor, being confined to the acute phase and positively correlated with the frequency of an activated memory splenic B cell population. We noticed the expansion of a splenic CD4 T cell population expressing CXCR5 and Bcl-6 during acute infection that was associated with the differentiation of the activated memory B cell population. Moreover, the number of splenic germinal centers peaked at one month after infection, hence paralleling the production of specific IgG. However, at chronic infection these populations contracted impacting the production of parasite-specific IgG. Our study provides new insights into the immune events taking place in a physiologically relevant host and a mechanistic basis for the inefficient humoral response during VL. © 2014 Rodrigues et al. |
Rossato, L G; Costa, V M; Dallegrave, E; Arbo, M; Silva, R; Ferreira, R; Amado, F; Dinis-Oliveira, R J; Duarte, J A; Bastos, De Lourdes M; Palmeira, C; Remião, F Mitochondrial cumulative damage induced by mitoxantrone: Late onset cardiac energetic impairment Journal Article 14 (1), pp. 30-40, 2014, (cited By 12). @article{Rossato201430, title = {Mitochondrial cumulative damage induced by mitoxantrone: Late onset cardiac energetic impairment}, author = {L G Rossato and V M Costa and E Dallegrave and M Arbo and R Silva and R Ferreira and F Amado and R J Dinis-Oliveira and J A Duarte and M De Lourdes Bastos and C Palmeira and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84895821912&doi=10.1007%2fs12012-013-9230-2&partnerID=40&md5=852423554938711bc111c26060e05733}, doi = {10.1007/s12012-013-9230-2}, year = {2014}, date = {2014-01-01}, volume = {14}, number = {1}, pages = {30-40}, abstract = {Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX-induced cardiotoxicity, namely the effects toward mitochondria using in vivo and in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate the early MTX cardiac toxic effects, while the other was euthanized on day 48 (MTX48), to allow the evaluation of MTX late cardiac effects. Cardiac mitochondria isolated from 4 adult untreated rats were also used to evaluate in vitro the MTX (10 nM, 100 nM, and 1 μM) direct effects upon mitochondria functionality. Two rats of MTX48 died on day 35, and MTX treatment caused a reduction in relative body weight gain in both treated groups with no significant changes in water and food intake. Decreased levels of plasma total creatine kinase and CK-MB were detected in the MTX22 group, and increased plasma levels of lactate were seen in MTX48. Increased cardiac relative mass and microscopic changes were evident in both treated groups. Considering mitochondrial effects, for the first time, it was evidenced that MTX induced an increase in the complex IV and complex V activities in MTX22 group, while a decrease in the complex V activity was accompanied by the reduction in ATP content in the MTX48 rats. No alterations in mitochondria transmembrane potential were found in isolated mitochondria from MTX48 rats or in isolated mitochondria directly incubated with MTX. This study highlights the relevance of the cumulative MTX-induced in vivo mitochondriopathy to the MTX cardiotoxicity. © 2013 Springer Science+Business Media New York.}, note = {cited By 12}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX-induced cardiotoxicity, namely the effects toward mitochondria using in vivo and in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate the early MTX cardiac toxic effects, while the other was euthanized on day 48 (MTX48), to allow the evaluation of MTX late cardiac effects. Cardiac mitochondria isolated from 4 adult untreated rats were also used to evaluate in vitro the MTX (10 nM, 100 nM, and 1 μM) direct effects upon mitochondria functionality. Two rats of MTX48 died on day 35, and MTX treatment caused a reduction in relative body weight gain in both treated groups with no significant changes in water and food intake. Decreased levels of plasma total creatine kinase and CK-MB were detected in the MTX22 group, and increased plasma levels of lactate were seen in MTX48. Increased cardiac relative mass and microscopic changes were evident in both treated groups. Considering mitochondrial effects, for the first time, it was evidenced that MTX induced an increase in the complex IV and complex V activities in MTX22 group, while a decrease in the complex V activity was accompanied by the reduction in ATP content in the MTX48 rats. No alterations in mitochondria transmembrane potential were found in isolated mitochondria from MTX48 rats or in isolated mitochondria directly incubated with MTX. This study highlights the relevance of the cumulative MTX-induced in vivo mitochondriopathy to the MTX cardiotoxicity. © 2013 Springer Science+Business Media New York. |
Dantas, S; Santos, A; Dias, I; Dinis-Oliveira, R J; Magalhães, T Parricide: A forensic approach Journal Article 22 , pp. 1-6, 2014, (cited By 8). @article{Dantas20141, title = {Parricide: A forensic approach}, author = {S Dantas and A Santos and I Dias and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84890499931&doi=10.1016%2fj.jflm.2013.11.008&partnerID=40&md5=594c01d86a76297155d7f46f6b1a9650}, doi = {10.1016/j.jflm.2013.11.008}, year = {2014}, date = {2014-01-01}, volume = {22}, pages = {1-6}, abstract = {Parricide is the act of murdering one's father (patricide), mother (matricide) or other close relative, but usually not children (infanticide). It is a rare event and little information is available on this topic. This study aims to increase knowledge about this phenomenon, promoting the timely detection of problematic cases and avoiding fatalities. A retrospective study based on the autopsy reports of parricide victims performed by the North Services of the National Institute of Legal Medicine and Forensic Sciences of Portugal between 2003 and 2011, as well as on the judicial outcome of each case, was performed. Seven cases of parricide were found, corresponding to 1.7% of all the homicides undergoing forensic evaluated. Victims and perpetrators were typically males. The assaults occurred all at home, in the presence of witnesses, and the perpetrator remained at the scene after the crime. The main alleged reasons were untreated psychiatric illness and financial conflicts in the cases of adult parricide, and attempts to protect the mother from intimate partner violence in younger ones. The judicial outcomes ranged from acquittal for nonimputability to conviction for murder, manslaughter or involuntary manslaughter. This study was carried out on a forensic sample and it is useful to implement strategies to prevent parricide. © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } Parricide is the act of murdering one's father (patricide), mother (matricide) or other close relative, but usually not children (infanticide). It is a rare event and little information is available on this topic. This study aims to increase knowledge about this phenomenon, promoting the timely detection of problematic cases and avoiding fatalities. A retrospective study based on the autopsy reports of parricide victims performed by the North Services of the National Institute of Legal Medicine and Forensic Sciences of Portugal between 2003 and 2011, as well as on the judicial outcome of each case, was performed. Seven cases of parricide were found, corresponding to 1.7% of all the homicides undergoing forensic evaluated. Victims and perpetrators were typically males. The assaults occurred all at home, in the presence of witnesses, and the perpetrator remained at the scene after the crime. The main alleged reasons were untreated psychiatric illness and financial conflicts in the cases of adult parricide, and attempts to protect the mother from intimate partner violence in younger ones. The judicial outcomes ranged from acquittal for nonimputability to conviction for murder, manslaughter or involuntary manslaughter. This study was carried out on a forensic sample and it is useful to implement strategies to prevent parricide. © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved. |
Dinis-Oliveira, R J; Magalhães, T; Moreira, R; Proença, J B; Pontes, H; Santos, A; Duarte, J A; Carvalho, F Clinical and forensic signs related to ethanol abuse: A mechanistic approach Journal Article 24 (2), pp. 81-110, 2014, (cited By 11). @article{Dinis-Oliveira201481, title = {Clinical and forensic signs related to ethanol abuse: A mechanistic approach}, author = {R J Dinis-Oliveira and T Magalhães and R Moreira and J B Proença and H Pontes and A Santos and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893304397&doi=10.3109%2f15376516.2013.869782&partnerID=40&md5=d865f143f09b45c11c73ce1b4bd179ab}, doi = {10.3109/15376516.2013.869782}, year = {2014}, date = {2014-01-01}, volume = {24}, number = {2}, pages = {81-110}, abstract = {For good performance in clinical and forensic toxicology, it is important to be aware of the signs and symptoms related to xenobiotic exposure since they will assist clinicians to reach a useful and rapid diagnosis. This manuscript highlights and critically analyses clinical and forensic imaging related to ethanol abuse. Here, signs that may lead to suspected ethanol abuse, but that are not necessarily related to liver disease are thoroughly discussed regarding its underlying mechanisms. This includes flushing and disulfiram reactions, urticaria, palmar erythema, spider telangiectasias, porphyria cutanea tarda, "paper money skin", psoriasis, rhinophyma, Dupuytren's contracture, multiple symmetrical lipomatosis (lipomatosis Lanois-Bensaude, Madelung's disease), pancreatitis-related signs, black hairy tongue, gout, nail changes, fetal alcohol syndrome, seborrheic dermatitis, sialosis and cancer. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.}, note = {cited By 11}, keywords = {}, pubstate = {published}, tppubtype = {article} } For good performance in clinical and forensic toxicology, it is important to be aware of the signs and symptoms related to xenobiotic exposure since they will assist clinicians to reach a useful and rapid diagnosis. This manuscript highlights and critically analyses clinical and forensic imaging related to ethanol abuse. Here, signs that may lead to suspected ethanol abuse, but that are not necessarily related to liver disease are thoroughly discussed regarding its underlying mechanisms. This includes flushing and disulfiram reactions, urticaria, palmar erythema, spider telangiectasias, porphyria cutanea tarda, "paper money skin", psoriasis, rhinophyma, Dupuytren's contracture, multiple symmetrical lipomatosis (lipomatosis Lanois-Bensaude, Madelung's disease), pancreatitis-related signs, black hairy tongue, gout, nail changes, fetal alcohol syndrome, seborrheic dermatitis, sialosis and cancer. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted. |
Pinto, Nóbrega A; Rodrigues, F; Dinis-Oliveira, R J; Magalhães, T Sexual Offenses Against Elderly People: Forensic Evaluation and Judicial Outcome Journal Article 26 (2), pp. 189-204, 2014, (cited By 3). @article{NóbregaPinto2014189, title = {Sexual Offenses Against Elderly People: Forensic Evaluation and Judicial Outcome}, author = {A Nóbrega Pinto and F Rodrigues and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893607429&doi=10.1080%2f08946566.2013.827951&partnerID=40&md5=1a3dbc7347ff812f58e44a941ba9e141}, doi = {10.1080/08946566.2013.827951}, year = {2014}, date = {2014-01-01}, volume = {26}, number = {2}, pages = {189-204}, abstract = {Forensic evaluation reports and judicial outcomes regarding older victims of suspected sexual offenses were retrospectively reviewed. During this period, a total of 14 cases were registered, corresponding to 0.3% of nonfatal crimes against elderly and 0.6% of the total of sexual crimes reported. All the victims were female. The majority lived alone and did not have limitations in communication, orientation, ambulation, or autonomy. The offenders were all male (17 to 81 years old); most were known to the victims and had history of previous disruptive behaviors. The majority of the sexual offenses occurred in the victims' homes, and the offenders tended to use physical violence. Forensic evaluation was crucial for the identification of physical and biological evidence, and forensic conclusions were positively correlated with the judicial outcome of each case. High prosecution and conviction rates were also observed. © 2014 Copyright Taylor and Francis Group, LLC.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Forensic evaluation reports and judicial outcomes regarding older victims of suspected sexual offenses were retrospectively reviewed. During this period, a total of 14 cases were registered, corresponding to 0.3% of nonfatal crimes against elderly and 0.6% of the total of sexual crimes reported. All the victims were female. The majority lived alone and did not have limitations in communication, orientation, ambulation, or autonomy. The offenders were all male (17 to 81 years old); most were known to the victims and had history of previous disruptive behaviors. The majority of the sexual offenses occurred in the victims' homes, and the offenders tended to use physical violence. Forensic evaluation was crucial for the identification of physical and biological evidence, and forensic conclusions were positively correlated with the judicial outcome of each case. High prosecution and conviction rates were also observed. © 2014 Copyright Taylor and Francis Group, LLC. |
Rossato, L G; Costa, V M; Dallegrave, E; Arbo, M; Dinis-Oliveira, R J; Santos-Silva, A; Duarte, J A; Bastos, De Lourdes M; Palmeira, C; Remião, F Cumulative mitoxantrone-induced haematological and hepatic adverse effects in a subchronic in vivo study Journal Article 114 (3), pp. 254-262, 2014, (cited By 6). @article{Rossato2014254, title = {Cumulative mitoxantrone-induced haematological and hepatic adverse effects in a subchronic in vivo study}, author = {L G Rossato and V M Costa and E Dallegrave and M Arbo and R J Dinis-Oliveira and A Santos-Silva and J A Duarte and M De Lourdes Bastos and C Palmeira and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893874423&doi=10.1111%2fbcpt.12143&partnerID=40&md5=66e9d632261dc9f1f343ebfa2ff25c1b}, doi = {10.1111/bcpt.12143}, year = {2014}, date = {2014-01-01}, volume = {114}, number = {3}, pages = {254-262}, abstract = {Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). |
Oliveira, A; Pinho, D; Albino-Teixeira, A; Medeiros, R; Dinis-Oliveira, R J; Carvalho, F Morphine glucuronidation increases its analgesic effect in guinea pigs Journal Article 109 (2), pp. 104-110, 2014, (cited By 2). @article{Oliveira2014104, title = {Morphine glucuronidation increases its analgesic effect in guinea pigs}, author = {A Oliveira and D Pinho and A Albino-Teixeira and R Medeiros and R J Dinis-Oliveira and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84907024435&doi=10.1016%2fj.lfs.2014.06.010&partnerID=40&md5=ed40eea10da925bf08f130bcfd6670af}, doi = {10.1016/j.lfs.2014.06.010}, year = {2014}, date = {2014-01-01}, volume = {109}, number = {2}, pages = {104-110}, abstract = {Aims: Morphine is extensively metabolized to neurotoxic morphine-3-glucuronide (M3G) and opioid agonist morphine-6-glucuronide (M6G). Due to these different roles, interindividual variability and co-administration of drugs that interfere with metabolism may affect analgesia. The aim of the study was to investigate the repercussions of administration of an inducer (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and an inhibitor (ranitidine) of glucuronidation in morphine metabolism and consequent analgesia, using the Guinea pig as a suitable model. Main methods: Thirty male Dunkin-Hartley guinea pigswere divided in six groups: control,morphine, ranitidine, ranitidine+ morphine, TCDDand TCDD+ morphine. After previous exposure to TCDDand ranitidine,morphine effect was assessed by an increasing temperature hotplate (35-52.5 °C), during 60min aftermorphine administration. Then, blood was collected and plasma morphine and metabolites were quantified. Key findings: Animals treated with TCDD presented faster analgesic effect and 75% reached the cut-off temperature of 52.5 °C, comparing with only 25% inmorphine group. Animals treatedwith ranitidine presented a significantly lower analgesic effect, compared with morphine group (p < 0.05). Moreover, significant differences between groups were found in M3G levels and M3G/morphine ratio (p < 0.001 and p < 0.0001), with TCDD animals presenting the highest values for M3G,M6G,M3G/morphine andM6G/morphine, and the lowest value for morphine. The opposite was observed in the animals treated with ranitidine. Significance: Our results indicate that modulation of morphine metabolismmay result in variations inmetabolite concentrations, leading to different analgesic responses tomorphine, in an animal model thatmay be used to improve morphine effect in clinical practice. © 2014 Elsevier Inc. All rights reserved. © 2014 Elsevier Inc. All rights reserved.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Aims: Morphine is extensively metabolized to neurotoxic morphine-3-glucuronide (M3G) and opioid agonist morphine-6-glucuronide (M6G). Due to these different roles, interindividual variability and co-administration of drugs that interfere with metabolism may affect analgesia. The aim of the study was to investigate the repercussions of administration of an inducer (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and an inhibitor (ranitidine) of glucuronidation in morphine metabolism and consequent analgesia, using the Guinea pig as a suitable model. Main methods: Thirty male Dunkin-Hartley guinea pigswere divided in six groups: control,morphine, ranitidine, ranitidine+ morphine, TCDDand TCDD+ morphine. After previous exposure to TCDDand ranitidine,morphine effect was assessed by an increasing temperature hotplate (35-52.5 °C), during 60min aftermorphine administration. Then, blood was collected and plasma morphine and metabolites were quantified. Key findings: Animals treated with TCDD presented faster analgesic effect and 75% reached the cut-off temperature of 52.5 °C, comparing with only 25% inmorphine group. Animals treatedwith ranitidine presented a significantly lower analgesic effect, compared with morphine group (p < 0.05). Moreover, significant differences between groups were found in M3G levels and M3G/morphine ratio (p < 0.001 and p < 0.0001), with TCDD animals presenting the highest values for M3G,M6G,M3G/morphine andM6G/morphine, and the lowest value for morphine. The opposite was observed in the animals treated with ranitidine. Significance: Our results indicate that modulation of morphine metabolismmay result in variations inmetabolite concentrations, leading to different analgesic responses tomorphine, in an animal model thatmay be used to improve morphine effect in clinical practice. © 2014 Elsevier Inc. All rights reserved. © 2014 Elsevier Inc. All rights reserved. |
Oliveira, A; Dinis-Oliveira, R J; Nogueira, A; Gonçalves, F; Silva, P; Vieira, C; Silvestre, R; Carvalho, F; Medeiros, R Interleukin-1β genotype and circulating levels in cancer patients: metastatic status and pain perception Journal Article 47 (13-14), pp. 1209-1213, 2014, (cited By 8). @article{Oliveira20141209b, title = {Interleukin-1β genotype and circulating levels in cancer patients: metastatic status and pain perception}, author = {A Oliveira and R J Dinis-Oliveira and A Nogueira and F Gonçalves and P Silva and C Vieira and R Silvestre and F Carvalho and R Medeiros}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929132258&doi=10.1016%2fj.clinbiochem.2014.04.009&partnerID=40&md5=cb1551aedbbc7689a554ec7f0c483ebd}, doi = {10.1016/j.clinbiochem.2014.04.009}, year = {2014}, date = {2014-01-01}, volume = {47}, number = {13-14}, pages = {1209-1213}, abstract = {OBJECTIVES: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients. DESIGN AND METHODS: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters. RESULTS: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVES: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients. DESIGN AND METHODS: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters. RESULTS: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074 |
Baltazar, M T; Dinis-Oliveira, R J; de Bastos, Lourdes M; Tsatsakis, A M; Duarte, J A; Carvalho, F Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases-A mechanistic approach Journal Article 230 (2), pp. 85-103, 2014, (cited By 96). @article{Baltazar201485, title = {Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases-A mechanistic approach}, author = {M T Baltazar and R J Dinis-Oliveira and M de Lourdes Bastos and A M Tsatsakis and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84907164920&doi=10.1016%2fj.toxlet.2014.01.039&partnerID=40&md5=6077546cf4a540cae54eab8e752da726}, doi = {10.1016/j.toxlet.2014.01.039}, year = {2014}, date = {2014-01-01}, volume = {230}, number = {2}, pages = {85-103}, abstract = {The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. © 2014 Elsevier Ireland Ltd.}, note = {cited By 96}, keywords = {}, pubstate = {published}, tppubtype = {article} } The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. © 2014 Elsevier Ireland Ltd. |
Silva, A C; Santos, L; Dinis-Oliveira, R J; Magalhães, T; Santos, A Sudden cardiac death in young adult Journal Article 14 (4), pp. 379-386, 2014, (cited By 2). @article{Silva2014379b, title = {Sudden cardiac death in young adult}, author = {A C Silva and L Santos and R J Dinis-Oliveira and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84936775039&doi=10.1007%2fs12012-014-9255-1&partnerID=40&md5=d78d411edf3308d2bdb3310f682d0b52}, doi = {10.1007/s12012-014-9255-1}, year = {2014}, date = {2014-01-01}, volume = {14}, number = {4}, pages = {379-386}, abstract = {Cardiovascular disease represents one of the most important public health problem in the Western countries, with sudden cardiac death (SCD) being the most common cause of death in adults under 65 years of age. The objective of the present study is to evaluate the leading causes of SCD in young adults who died suddenly in Northern Portugal between 2007 and 2012. This study included 288 cases of 20- to 45-year-old adults who died suddenly of a cardiac cause and whose forensic autopsy was performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences between 2007 and 2012. Data included the cause of death, forensic autopsy findings, previous medical history and cardiovascular risk factors. The mean age of the population was 37.36 years. Coronary artery disease (CAD) was the leading cause of death, representing 55.6 % of all cases (92.5 % of men and 7.5 % of women). Females died mostly from probable primary arrhythmia. From those who died of coronary disease, 72 (25 % of total cases) had histological evidence of a fatal acute infarction. Age, previous coronary disease, hypercholesterolemia, smoking habits and alcohol consumption seem to be associated with an increased risk of SCD by CAD. A total of 55.6 % of deaths were attributed to CAD. Prevention of cardiovascular risk factors should therefore be considered to prevent atherosclerosis in young adults.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cardiovascular disease represents one of the most important public health problem in the Western countries, with sudden cardiac death (SCD) being the most common cause of death in adults under 65 years of age. The objective of the present study is to evaluate the leading causes of SCD in young adults who died suddenly in Northern Portugal between 2007 and 2012. This study included 288 cases of 20- to 45-year-old adults who died suddenly of a cardiac cause and whose forensic autopsy was performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences between 2007 and 2012. Data included the cause of death, forensic autopsy findings, previous medical history and cardiovascular risk factors. The mean age of the population was 37.36 years. Coronary artery disease (CAD) was the leading cause of death, representing 55.6 % of all cases (92.5 % of men and 7.5 % of women). Females died mostly from probable primary arrhythmia. From those who died of coronary disease, 72 (25 % of total cases) had histological evidence of a fatal acute infarction. Age, previous coronary disease, hypercholesterolemia, smoking habits and alcohol consumption seem to be associated with an increased risk of SCD by CAD. A total of 55.6 % of deaths were attributed to CAD. Prevention of cardiovascular risk factors should therefore be considered to prevent atherosclerosis in young adults. |
Dinis-Oliveira, R J Licit and ilicit uses of medicines [Usos Lícito e Ilícito dos Fármacos] Journal Article Acta Medica Portuguesa, 27 (6), pp. 755-766, 2014, (cited By 3). @article{Dinis-Oliveira2014755b, title = {Licit and ilicit uses of medicines [Usos Lícito e Ilícito dos Fármacos]}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84920111686&partnerID=40&md5=ad15ceca68ddcdbc7aec0e9e00346389}, year = {2014}, date = {2014-01-01}, journal = {Acta Medica Portuguesa}, volume = {27}, number = {6}, pages = {755-766}, abstract = {Drugs of abuse are a heterogeneous group of xenobiotics or endobiotics that alter synaptic organization in the central nervous system in a transient or permanent basis, often leading to a compulsively use. What unites its members is that they confer pleasure (hedonism) to the abusers, namely by their action in the mesolimbic dopamine system. To exert its effects, different drugs of abuse will act on receptors and neurotransmitter transporters, modeling neurotransmitter release into the synaptic cleft. Besides acting on presynaptic neurons also function in neurotransmitter receptors and ion channels in postsynaptic neurons, thereby modifying the signaling pathways. In this work, the pharmacodynamic and the potential of some psychoactive substances that are typically subjected to abuse in Portugal, is reviewed. With this approach it was also possible a discussion of drugs of abuse that exhibit very different toxicological effects such as stimulants, depressants and hallucinogens. Particularly, the potential to induce dependence and addition, as well as to undergo illicit and licit uses, of central nervous system depressants, stimulants, anticholinergic antiparkinson drugs, opioids, cannabinoids and hallucinogens, is discussed. © Ordem dos Médicos 2014.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Drugs of abuse are a heterogeneous group of xenobiotics or endobiotics that alter synaptic organization in the central nervous system in a transient or permanent basis, often leading to a compulsively use. What unites its members is that they confer pleasure (hedonism) to the abusers, namely by their action in the mesolimbic dopamine system. To exert its effects, different drugs of abuse will act on receptors and neurotransmitter transporters, modeling neurotransmitter release into the synaptic cleft. Besides acting on presynaptic neurons also function in neurotransmitter receptors and ion channels in postsynaptic neurons, thereby modifying the signaling pathways. In this work, the pharmacodynamic and the potential of some psychoactive substances that are typically subjected to abuse in Portugal, is reviewed. With this approach it was also possible a discussion of drugs of abuse that exhibit very different toxicological effects such as stimulants, depressants and hallucinogens. Particularly, the potential to induce dependence and addition, as well as to undergo illicit and licit uses, of central nervous system depressants, stimulants, anticholinergic antiparkinson drugs, opioids, cannabinoids and hallucinogens, is discussed. © Ordem dos Médicos 2014. |
Baltazar, M T; Dinis-Oliveira, R J; de Bastos, Lourdes M; Tsatsakis, A M; Duarte, J A; Carvalho, F Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases-A mechanistic approach Journal Article Toxicology Letters, 230 (2), pp. 85-103, 2014, (cited By 131). @article{Baltazar201485b, title = {Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases-A mechanistic approach}, author = {M T Baltazar and R J Dinis-Oliveira and M de Lourdes Bastos and A M Tsatsakis and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84907164920&doi=10.1016%2fj.toxlet.2014.01.039&partnerID=40&md5=6077546cf4a540cae54eab8e752da726}, doi = {10.1016/j.toxlet.2014.01.039}, year = {2014}, date = {2014-01-01}, journal = {Toxicology Letters}, volume = {230}, number = {2}, pages = {85-103}, abstract = {The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. © 2014 Elsevier Ireland Ltd.}, note = {cited By 131}, keywords = {}, pubstate = {published}, tppubtype = {article} } The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. © 2014 Elsevier Ireland Ltd. |
Oliveira, A; Pinho, D; Albino-Teixeira, A; Medeiros, R; Dinis-Oliveira, R J; Carvalho, F Morphine glucuronidation increases its analgesic effect in guinea pigs Journal Article Life Sciences, 109 (2), pp. 104-110, 2014, (cited By 4). @article{Oliveira2014104b, title = {Morphine glucuronidation increases its analgesic effect in guinea pigs}, author = {A Oliveira and D Pinho and A Albino-Teixeira and R Medeiros and R J Dinis-Oliveira and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84907024435&doi=10.1016%2fj.lfs.2014.06.010&partnerID=40&md5=ed40eea10da925bf08f130bcfd6670af}, doi = {10.1016/j.lfs.2014.06.010}, year = {2014}, date = {2014-01-01}, journal = {Life Sciences}, volume = {109}, number = {2}, pages = {104-110}, abstract = {Aims: Morphine is extensively metabolized to neurotoxic morphine-3-glucuronide (M3G) and opioid agonist morphine-6-glucuronide (M6G). Due to these different roles, interindividual variability and co-administration of drugs that interfere with metabolism may affect analgesia. The aim of the study was to investigate the repercussions of administration of an inducer (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and an inhibitor (ranitidine) of glucuronidation in morphine metabolism and consequent analgesia, using the Guinea pig as a suitable model. Main methods: Thirty male Dunkin-Hartley guinea pigswere divided in six groups: control,morphine, ranitidine, ranitidine+ morphine, TCDDand TCDD+ morphine. After previous exposure to TCDDand ranitidine,morphine effect was assessed by an increasing temperature hotplate (35-52.5 °C), during 60min aftermorphine administration. Then, blood was collected and plasma morphine and metabolites were quantified. Key findings: Animals treated with TCDD presented faster analgesic effect and 75% reached the cut-off temperature of 52.5 °C, comparing with only 25% inmorphine group. Animals treatedwith ranitidine presented a significantly lower analgesic effect, compared with morphine group (p < 0.05). Moreover, significant differences between groups were found in M3G levels and M3G/morphine ratio (p < 0.001 and p < 0.0001), with TCDD animals presenting the highest values for M3G,M6G,M3G/morphine andM6G/morphine, and the lowest value for morphine. The opposite was observed in the animals treated with ranitidine. Significance: Our results indicate that modulation of morphine metabolismmay result in variations inmetabolite concentrations, leading to different analgesic responses tomorphine, in an animal model thatmay be used to improve morphine effect in clinical practice. © 2014 Elsevier Inc. All rights reserved. © 2014 Elsevier Inc. All rights reserved.}, note = {cited By 4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Aims: Morphine is extensively metabolized to neurotoxic morphine-3-glucuronide (M3G) and opioid agonist morphine-6-glucuronide (M6G). Due to these different roles, interindividual variability and co-administration of drugs that interfere with metabolism may affect analgesia. The aim of the study was to investigate the repercussions of administration of an inducer (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and an inhibitor (ranitidine) of glucuronidation in morphine metabolism and consequent analgesia, using the Guinea pig as a suitable model. Main methods: Thirty male Dunkin-Hartley guinea pigswere divided in six groups: control,morphine, ranitidine, ranitidine+ morphine, TCDDand TCDD+ morphine. After previous exposure to TCDDand ranitidine,morphine effect was assessed by an increasing temperature hotplate (35-52.5 °C), during 60min aftermorphine administration. Then, blood was collected and plasma morphine and metabolites were quantified. Key findings: Animals treated with TCDD presented faster analgesic effect and 75% reached the cut-off temperature of 52.5 °C, comparing with only 25% inmorphine group. Animals treatedwith ranitidine presented a significantly lower analgesic effect, compared with morphine group (p < 0.05). Moreover, significant differences between groups were found in M3G levels and M3G/morphine ratio (p < 0.001 and p < 0.0001), with TCDD animals presenting the highest values for M3G,M6G,M3G/morphine andM6G/morphine, and the lowest value for morphine. The opposite was observed in the animals treated with ranitidine. Significance: Our results indicate that modulation of morphine metabolismmay result in variations inmetabolite concentrations, leading to different analgesic responses tomorphine, in an animal model thatmay be used to improve morphine effect in clinical practice. © 2014 Elsevier Inc. All rights reserved. © 2014 Elsevier Inc. All rights reserved. |
Pinto, Nóbrega A; Rodrigues, F; Dinis-Oliveira, R J; Magalhães, T Sexual Offenses Against Elderly People: Forensic Evaluation and Judicial Outcome Journal Article Journal of Elder Abuse and Neglect, 26 (2), pp. 189-204, 2014, (cited By 6). @article{NóbregaPinto2014189b, title = {Sexual Offenses Against Elderly People: Forensic Evaluation and Judicial Outcome}, author = {A Nóbrega Pinto and F Rodrigues and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893607429&doi=10.1080%2f08946566.2013.827951&partnerID=40&md5=1a3dbc7347ff812f58e44a941ba9e141}, doi = {10.1080/08946566.2013.827951}, year = {2014}, date = {2014-01-01}, journal = {Journal of Elder Abuse and Neglect}, volume = {26}, number = {2}, pages = {189-204}, abstract = {Forensic evaluation reports and judicial outcomes regarding older victims of suspected sexual offenses were retrospectively reviewed. During this period, a total of 14 cases were registered, corresponding to 0.3% of nonfatal crimes against elderly and 0.6% of the total of sexual crimes reported. All the victims were female. The majority lived alone and did not have limitations in communication, orientation, ambulation, or autonomy. The offenders were all male (17 to 81 years old); most were known to the victims and had history of previous disruptive behaviors. The majority of the sexual offenses occurred in the victims' homes, and the offenders tended to use physical violence. Forensic evaluation was crucial for the identification of physical and biological evidence, and forensic conclusions were positively correlated with the judicial outcome of each case. High prosecution and conviction rates were also observed. © 2014 Copyright Taylor and Francis Group, LLC.}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } Forensic evaluation reports and judicial outcomes regarding older victims of suspected sexual offenses were retrospectively reviewed. During this period, a total of 14 cases were registered, corresponding to 0.3% of nonfatal crimes against elderly and 0.6% of the total of sexual crimes reported. All the victims were female. The majority lived alone and did not have limitations in communication, orientation, ambulation, or autonomy. The offenders were all male (17 to 81 years old); most were known to the victims and had history of previous disruptive behaviors. The majority of the sexual offenses occurred in the victims' homes, and the offenders tended to use physical violence. Forensic evaluation was crucial for the identification of physical and biological evidence, and forensic conclusions were positively correlated with the judicial outcome of each case. High prosecution and conviction rates were also observed. © 2014 Copyright Taylor and Francis Group, LLC. |
Rossato, L G; Costa, V M; Dallegrave, E; Arbo, M; Dinis-Oliveira, R J; Santos-Silva, A; Duarte, J A; Bastos, De Lourdes M; Palmeira, C; Remião, F Cumulative mitoxantrone-induced haematological and hepatic adverse effects in a subchronic in vivo study Journal Article Basic and Clinical Pharmacology and Toxicology, 114 (3), pp. 254-262, 2014, (cited By 6). @article{Rossato2014254b, title = {Cumulative mitoxantrone-induced haematological and hepatic adverse effects in a subchronic in vivo study}, author = {L G Rossato and V M Costa and E Dallegrave and M Arbo and R J Dinis-Oliveira and A Santos-Silva and J A Duarte and M De Lourdes Bastos and C Palmeira and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893874423&doi=10.1111%2fbcpt.12143&partnerID=40&md5=66e9d632261dc9f1f343ebfa2ff25c1b}, doi = {10.1111/bcpt.12143}, year = {2014}, date = {2014-01-01}, journal = {Basic and Clinical Pharmacology and Toxicology}, volume = {114}, number = {3}, pages = {254-262}, abstract = {Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. © 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). |
Dantas, S; Santos, A; Dias, I; Dinis-Oliveira, R J; Magalhães, T Parricide: A forensic approach Journal Article Journal of Forensic and Legal Medicine, 22 , pp. 1-6, 2014, (cited By 9). @article{Dantas20141b, title = {Parricide: A forensic approach}, author = {S Dantas and A Santos and I Dias and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84890499931&doi=10.1016%2fj.jflm.2013.11.008&partnerID=40&md5=594c01d86a76297155d7f46f6b1a9650}, doi = {10.1016/j.jflm.2013.11.008}, year = {2014}, date = {2014-01-01}, journal = {Journal of Forensic and Legal Medicine}, volume = {22}, pages = {1-6}, abstract = {Parricide is the act of murdering one's father (patricide), mother (matricide) or other close relative, but usually not children (infanticide). It is a rare event and little information is available on this topic. This study aims to increase knowledge about this phenomenon, promoting the timely detection of problematic cases and avoiding fatalities. A retrospective study based on the autopsy reports of parricide victims performed by the North Services of the National Institute of Legal Medicine and Forensic Sciences of Portugal between 2003 and 2011, as well as on the judicial outcome of each case, was performed. Seven cases of parricide were found, corresponding to 1.7% of all the homicides undergoing forensic evaluated. Victims and perpetrators were typically males. The assaults occurred all at home, in the presence of witnesses, and the perpetrator remained at the scene after the crime. The main alleged reasons were untreated psychiatric illness and financial conflicts in the cases of adult parricide, and attempts to protect the mother from intimate partner violence in younger ones. The judicial outcomes ranged from acquittal for nonimputability to conviction for murder, manslaughter or involuntary manslaughter. This study was carried out on a forensic sample and it is useful to implement strategies to prevent parricide. © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.}, note = {cited By 9}, keywords = {}, pubstate = {published}, tppubtype = {article} } Parricide is the act of murdering one's father (patricide), mother (matricide) or other close relative, but usually not children (infanticide). It is a rare event and little information is available on this topic. This study aims to increase knowledge about this phenomenon, promoting the timely detection of problematic cases and avoiding fatalities. A retrospective study based on the autopsy reports of parricide victims performed by the North Services of the National Institute of Legal Medicine and Forensic Sciences of Portugal between 2003 and 2011, as well as on the judicial outcome of each case, was performed. Seven cases of parricide were found, corresponding to 1.7% of all the homicides undergoing forensic evaluated. Victims and perpetrators were typically males. The assaults occurred all at home, in the presence of witnesses, and the perpetrator remained at the scene after the crime. The main alleged reasons were untreated psychiatric illness and financial conflicts in the cases of adult parricide, and attempts to protect the mother from intimate partner violence in younger ones. The judicial outcomes ranged from acquittal for nonimputability to conviction for murder, manslaughter or involuntary manslaughter. This study was carried out on a forensic sample and it is useful to implement strategies to prevent parricide. © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved. |
Dinis-Oliveira, R J; Magalhães, T; Moreira, R; Proença, J B; Pontes, H; Santos, A; Duarte, J A; Carvalho, F Clinical and forensic signs related to ethanol abuse: A mechanistic approach Journal Article Toxicology Mechanisms and Methods, 24 (2), pp. 81-110, 2014, (cited By 11). @article{Dinis-Oliveira201481b, title = {Clinical and forensic signs related to ethanol abuse: A mechanistic approach}, author = {R J Dinis-Oliveira and T Magalhães and R Moreira and J B Proença and H Pontes and A Santos and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893304397&doi=10.3109%2f15376516.2013.869782&partnerID=40&md5=d865f143f09b45c11c73ce1b4bd179ab}, doi = {10.3109/15376516.2013.869782}, year = {2014}, date = {2014-01-01}, journal = {Toxicology Mechanisms and Methods}, volume = {24}, number = {2}, pages = {81-110}, abstract = {For good performance in clinical and forensic toxicology, it is important to be aware of the signs and symptoms related to xenobiotic exposure since they will assist clinicians to reach a useful and rapid diagnosis. This manuscript highlights and critically analyses clinical and forensic imaging related to ethanol abuse. Here, signs that may lead to suspected ethanol abuse, but that are not necessarily related to liver disease are thoroughly discussed regarding its underlying mechanisms. This includes flushing and disulfiram reactions, urticaria, palmar erythema, spider telangiectasias, porphyria cutanea tarda, "paper money skin", psoriasis, rhinophyma, Dupuytren's contracture, multiple symmetrical lipomatosis (lipomatosis Lanois-Bensaude, Madelung's disease), pancreatitis-related signs, black hairy tongue, gout, nail changes, fetal alcohol syndrome, seborrheic dermatitis, sialosis and cancer. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.}, note = {cited By 11}, keywords = {}, pubstate = {published}, tppubtype = {article} } For good performance in clinical and forensic toxicology, it is important to be aware of the signs and symptoms related to xenobiotic exposure since they will assist clinicians to reach a useful and rapid diagnosis. This manuscript highlights and critically analyses clinical and forensic imaging related to ethanol abuse. Here, signs that may lead to suspected ethanol abuse, but that are not necessarily related to liver disease are thoroughly discussed regarding its underlying mechanisms. This includes flushing and disulfiram reactions, urticaria, palmar erythema, spider telangiectasias, porphyria cutanea tarda, "paper money skin", psoriasis, rhinophyma, Dupuytren's contracture, multiple symmetrical lipomatosis (lipomatosis Lanois-Bensaude, Madelung's disease), pancreatitis-related signs, black hairy tongue, gout, nail changes, fetal alcohol syndrome, seborrheic dermatitis, sialosis and cancer. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted. |
Dinis-Oliveira, R J Heterogeneous and homogeneous immunoassays for drug analysis Journal Article Bioanalysis, 6 (21), pp. 2877-2896, 2014, (cited By 14). @article{Dinis-Oliveira20142877b, title = {Heterogeneous and homogeneous immunoassays for drug analysis}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84918500311&doi=10.4155%2fbio.14.208&partnerID=40&md5=3466196652b70cf9d8f81e1d6010cae7}, doi = {10.4155/bio.14.208}, year = {2014}, date = {2014-01-01}, journal = {Bioanalysis}, volume = {6}, number = {21}, pages = {2877-2896}, abstract = {Immunoassays are very useful techniques to perform screening and semi-quantitative analysis of hundreds of different xenobiotics. Small sample volumes are required and pretreatment is usually unnecessary (e.g., homogeneous immunoassays). Fully automated and high-throughput systems are available, which help physicians to take timely decisions. However, immunoassays do suffer from interference from both endogenous and exogenous factors that limit their application in quantitative analysis. These assays use different labels (e.g., colorimetric, fluorescent, chemiluminescent or electrochemiluminescent) and different methods for generating and measuring signals, but the basic principles are usually similar. This review outlines the practical aspects of immunoassays in bioanalysis and describes their application in clinical chemistry for xenobiotic analysis, namely medicines and drugs of abuse. © 2014 Future Science Ltd.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } Immunoassays are very useful techniques to perform screening and semi-quantitative analysis of hundreds of different xenobiotics. Small sample volumes are required and pretreatment is usually unnecessary (e.g., homogeneous immunoassays). Fully automated and high-throughput systems are available, which help physicians to take timely decisions. However, immunoassays do suffer from interference from both endogenous and exogenous factors that limit their application in quantitative analysis. These assays use different labels (e.g., colorimetric, fluorescent, chemiluminescent or electrochemiluminescent) and different methods for generating and measuring signals, but the basic principles are usually similar. This review outlines the practical aspects of immunoassays in bioanalysis and describes their application in clinical chemistry for xenobiotic analysis, namely medicines and drugs of abuse. © 2014 Future Science Ltd. |
Dinis-Oliveira, R J Metabolomics of drugs of abuse: A more realistic view of the toxicological complexity Journal Article Bioanalysis, 6 (23), pp. 3155-3159, 2014, (cited By 28). @article{Dinis-Oliveira20143155b, title = {Metabolomics of drugs of abuse: A more realistic view of the toxicological complexity}, author = {R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84919783310&doi=10.4155%2fbio.14.260&partnerID=40&md5=437452c2d0a0f295a5e47062021b34ff}, doi = {10.4155/bio.14.260}, year = {2014}, date = {2014-01-01}, journal = {Bioanalysis}, volume = {6}, number = {23}, pages = {3155-3159}, note = {cited By 28}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Magalhães, T; Dinis-Oliveira, R J; Santos, A Teaching forensic medicine in the University of Porto Journal Article Journal of Forensic and Legal Medicine, 25 , pp. 45-48, 2014, (cited By 6). @article{Magalhães201445b, title = {Teaching forensic medicine in the University of Porto}, author = {T Magalhães and R J Dinis-Oliveira and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84900402225&doi=10.1016%2fj.jflm.2014.04.011&partnerID=40&md5=bb65c0572416a1c886a1c108739114ad}, doi = {10.1016/j.jflm.2014.04.011}, year = {2014}, date = {2014-01-01}, journal = {Journal of Forensic and Legal Medicine}, volume = {25}, pages = {45-48}, abstract = {The University of Porto (UP) provides education in Forensic Medicine (FM) through the 1st, 2nd and 3rd cycle of studies, post-graduation and continuing education courses. This education is related to forensic pathology, clinical forensic medicine (including forensic psychology and psychiatry), forensic chemistry and toxicology, forensic genetics and biology, and criminalistics. With this work we intent to reflect on how we are currently teaching FM in the UP, at all levels of university graduation. We will present our models, regarding the educational objectives, curricular program and teaching/learning methodologies of each cycle of studies as well as in post-graduate and continuing education courses. Historically, and besides related administratively to the Ministry of Justice, the Portuguese Medico-Legal Institutes (since 1918) and more recently the National Institute of Legal Medicine and Forensic Sciences (INMLCF) also have educational and research responsibilities. Thus, it lends space and cooperates with academic institutions and this contribution, namely regarding teaching forensic sciences in Portugal has been judged as an example for other Countries. This contribution is so important that in UP, the Department of Legal Medicine and Forensic Sciences of the Faculty of Medicine (FMUP) shares, until now, the same physical space with North Branch of the INMLCF, which represents a notorious advantage, since it makes possible the "learning by doing". © 2014 Elsevier Ltd. All rights reserved.}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } The University of Porto (UP) provides education in Forensic Medicine (FM) through the 1st, 2nd and 3rd cycle of studies, post-graduation and continuing education courses. This education is related to forensic pathology, clinical forensic medicine (including forensic psychology and psychiatry), forensic chemistry and toxicology, forensic genetics and biology, and criminalistics. With this work we intent to reflect on how we are currently teaching FM in the UP, at all levels of university graduation. We will present our models, regarding the educational objectives, curricular program and teaching/learning methodologies of each cycle of studies as well as in post-graduate and continuing education courses. Historically, and besides related administratively to the Ministry of Justice, the Portuguese Medico-Legal Institutes (since 1918) and more recently the National Institute of Legal Medicine and Forensic Sciences (INMLCF) also have educational and research responsibilities. Thus, it lends space and cooperates with academic institutions and this contribution, namely regarding teaching forensic sciences in Portugal has been judged as an example for other Countries. This contribution is so important that in UP, the Department of Legal Medicine and Forensic Sciences of the Faculty of Medicine (FMUP) shares, until now, the same physical space with North Branch of the INMLCF, which represents a notorious advantage, since it makes possible the "learning by doing". © 2014 Elsevier Ltd. All rights reserved. |
Falcão, V; Jardim, P; Dinis-Oliveira, R J; Magalhães, T Forensic evaluation in alleged sibling incest against children Journal Article Journal of Child Sexual Abuse, 23 (7), pp. 755-767, 2014, (cited By 3). @article{Falcão2014755b, title = {Forensic evaluation in alleged sibling incest against children}, author = {V Falcão and P Jardim and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84918530056&doi=10.1080%2f10538712.2014.949394&partnerID=40&md5=0a649c6716290fbe6bc05cb1e1b153cd}, doi = {10.1080/10538712.2014.949394}, year = {2014}, date = {2014-01-01}, journal = {Journal of Child Sexual Abuse}, volume = {23}, number = {7}, pages = {755-767}, abstract = {Sibling incest is a serious form of intrafamilial sexual abuse with health, social, and legal relevance. A retrospective study was conducted through the analysis of forensic medical reports of the alleged sibling incest of victims under 18 years old ( n = 68) from 2004 to 2011 as well as the respective judicial outcomes. Results demonstrated that sibling's sexual abuse is associated with several circumstances that might exacerbate its severity such as vaginal, anal, and/or oral penetration. Moreover, the victim's young age, the proximity between victim and abuser, and the fact that it is committed at the victim's and /or abuser's home and by using physical violence and verbal threats justify a late detection of these cases. Copyright © Taylor & Francis Group, LLC.}, note = {cited By 3}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sibling incest is a serious form of intrafamilial sexual abuse with health, social, and legal relevance. A retrospective study was conducted through the analysis of forensic medical reports of the alleged sibling incest of victims under 18 years old ( n = 68) from 2004 to 2011 as well as the respective judicial outcomes. Results demonstrated that sibling's sexual abuse is associated with several circumstances that might exacerbate its severity such as vaginal, anal, and/or oral penetration. Moreover, the victim's young age, the proximity between victim and abuser, and the fact that it is committed at the victim's and /or abuser's home and by using physical violence and verbal threats justify a late detection of these cases. Copyright © Taylor & Francis Group, LLC. |
Silva, A C; Santos, L; Dinis-Oliveira, R J; Magalhães, T; Santos, A Sudden Cardiac Death in Young Adult Journal Article Cardiovascular Toxicology, 14 (4), pp. 379-386, 2014, (cited By 2). @article{Silva2014379c, title = {Sudden Cardiac Death in Young Adult}, author = {A C Silva and L Santos and R J Dinis-Oliveira and T Magalhães and A Santos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897358684&doi=10.1007%2fs12012-014-9255-1&partnerID=40&md5=33b8d5856968d5c2971b6204c5a530e3}, doi = {10.1007/s12012-014-9255-1}, year = {2014}, date = {2014-01-01}, journal = {Cardiovascular Toxicology}, volume = {14}, number = {4}, pages = {379-386}, abstract = {Cardiovascular disease represents one of the most important public health problem in the Western countries, with sudden cardiac death (SCD) being the most common cause of death in adults under 65 years of age. The objective of the present study is to evaluate the leading causes of SCD in young adults who died suddenly in Northern Portugal between 2007 and 2012. This study included 288 cases of 20- to 45-year-old adults who died suddenly of a cardiac cause and whose forensic autopsy was performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences between 2007 and 2012. Data included the cause of death, forensic autopsy findings, previous medical history and cardiovascular risk factors. The mean age of the population was 37.36 years. Coronary artery disease (CAD) was the leading cause of death, representing 55.6 % of all cases (92.5 % of men and 7.5 % of women). Females died mostly from probable primary arrhythmia. From those who died of coronary disease, 72 (25 % of total cases) had histological evidence of a fatal acute infarction. Age, previous coronary disease, hypercholesterolemia, smoking habits and alcohol consumption seem to be associated with an increased risk of SCD by CAD. A total of 55.6 % of deaths were attributed to CAD. Prevention of cardiovascular risk factors should therefore be considered to prevent atherosclerosis in young adults. © 2014, Springer Science+Business Media New York.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cardiovascular disease represents one of the most important public health problem in the Western countries, with sudden cardiac death (SCD) being the most common cause of death in adults under 65 years of age. The objective of the present study is to evaluate the leading causes of SCD in young adults who died suddenly in Northern Portugal between 2007 and 2012. This study included 288 cases of 20- to 45-year-old adults who died suddenly of a cardiac cause and whose forensic autopsy was performed in the North Branch of the National Institute of Legal Medicine and Forensic Sciences between 2007 and 2012. Data included the cause of death, forensic autopsy findings, previous medical history and cardiovascular risk factors. The mean age of the population was 37.36 years. Coronary artery disease (CAD) was the leading cause of death, representing 55.6 % of all cases (92.5 % of men and 7.5 % of women). Females died mostly from probable primary arrhythmia. From those who died of coronary disease, 72 (25 % of total cases) had histological evidence of a fatal acute infarction. Age, previous coronary disease, hypercholesterolemia, smoking habits and alcohol consumption seem to be associated with an increased risk of SCD by CAD. A total of 55.6 % of deaths were attributed to CAD. Prevention of cardiovascular risk factors should therefore be considered to prevent atherosclerosis in young adults. © 2014, Springer Science+Business Media New York. |
Gomes, V; Jardim, P; Taveira, F; Dinis-Oliveira, R J; Magalhães, T Alleged Biological Father Incest: A Forensic Approach Journal Article Journal of Forensic Sciences, 59 (1), pp. 255-259, 2014, (cited By 8). @article{Gomes2014255b, title = {Alleged Biological Father Incest: A Forensic Approach}, author = {V Gomes and P Jardim and F Taveira and R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84891835706&doi=10.1111%2f1556-4029.12310&partnerID=40&md5=9071801769865d3680eb969120d7ab52}, doi = {10.1111/1556-4029.12310}, year = {2014}, date = {2014-01-01}, journal = {Journal of Forensic Sciences}, volume = {59}, number = {1}, pages = {255-259}, abstract = {Paternal incest is one of the most serious forms of intrafamilial sexual abuse with clinical, social, and legal relevance. A retrospective study was performed, based on forensic reports and judicial decisions of alleged cases of biological paternal incest of victims under 18 years old (n = 215) from 2003 to 2008. Results highlight that in a relevant number of cases: victims were female; the abuse begun at an early age with reiteration; the alleged perpetrator presented a history of sexual crimes against children; sexual practices were physically poorly intrusive, which associated with a forensic medical evaluation performed more than 72 h after the abuse, explain partially the absence of physical injuries or other evidence-these last aspects are different from extrafamilial cases. In conclusion, observations about paternal incest are likely to exacerbate the psychosocial consequences of the abuse and may explain the difficulty and delay in detect and disclose these cases. Few cases were legally prosecuted and convicted. © 2013 American Academy of Forensic Sciences.}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } Paternal incest is one of the most serious forms of intrafamilial sexual abuse with clinical, social, and legal relevance. A retrospective study was performed, based on forensic reports and judicial decisions of alleged cases of biological paternal incest of victims under 18 years old (n = 215) from 2003 to 2008. Results highlight that in a relevant number of cases: victims were female; the abuse begun at an early age with reiteration; the alleged perpetrator presented a history of sexual crimes against children; sexual practices were physically poorly intrusive, which associated with a forensic medical evaluation performed more than 72 h after the abuse, explain partially the absence of physical injuries or other evidence-these last aspects are different from extrafamilial cases. In conclusion, observations about paternal incest are likely to exacerbate the psychosocial consequences of the abuse and may explain the difficulty and delay in detect and disclose these cases. Few cases were legally prosecuted and convicted. © 2013 American Academy of Forensic Sciences. |
Baltazar, M T; Dinis-Oliveira, R J; Bastos, M D L; Duarte, J A; Carvalho, F Lysine acetylsalicylate improves the safety of paraquat formulation in rats by increasing its elimination and preventing lung and kidney injury Journal Article Toxicology Research, 3 (4), pp. 266-277, 2014, (cited By 2). @article{Baltazar2014266b, title = {Lysine acetylsalicylate improves the safety of paraquat formulation in rats by increasing its elimination and preventing lung and kidney injury}, author = {M T Baltazar and R J Dinis-Oliveira and M D L Bastos and J A Duarte and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84902356900&doi=10.1039%2fc3tx50102g&partnerID=40&md5=f758f62054cb8885f7fbfec7101abeaf}, doi = {10.1039/c3tx50102g}, year = {2014}, date = {2014-01-01}, journal = {Toxicology Research}, volume = {3}, number = {4}, pages = {266-277}, abstract = {The incorporation of lysine acetylsalicylate (LAS) in the commercial formulation of paraquat (PQ), Gramoxone®, has been shown to significantly increase the survival of intoxicated mammals while maintaining the herbicidal effect. The aim of the present study was to clarify the mechanisms involved in the protective effect of LAS in a rodent model through monitoring PQ levels and the histological and biochemical biomarkers of toxicity in male Wistar rats following intoxication with PQ formulations in the absence and presence of LAS. Gramoxone® and the formulation with LAS were administered by gavage at the doses of 125 mg kg-1 of PQ and 125 mg kg-1 of PQ + 316 mg kg-1 of LAS, respectively. The obtained results showed that LAS improves the safety of PQ formulation by increasing its elimination and preventing lung and kidney injury. LAS prevented the biochemical and histological alterations in lung induced by PQ measured at the end of 24 h and 48 h. This was evidenced by a significant reduction in lipid peroxidation, the maintenance of reduced glutathione levels and decreased levels of oxidized glutathione, as well as the normalization of the urinary biomarkers, creatinine and N-acetyl-β-glucosaminidase. LAS treatment also caused a significant reduction in PQ-induced activation of nuclear factor kappa B (NF-κB) in the lung. The results allow us to conclude that lysine acetylsalicylate improves the safety of PQ formulation in rats by increasing its elimination and preventing lung and kidney injury. This journal is © the Partner Organisations 2014.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } The incorporation of lysine acetylsalicylate (LAS) in the commercial formulation of paraquat (PQ), Gramoxone®, has been shown to significantly increase the survival of intoxicated mammals while maintaining the herbicidal effect. The aim of the present study was to clarify the mechanisms involved in the protective effect of LAS in a rodent model through monitoring PQ levels and the histological and biochemical biomarkers of toxicity in male Wistar rats following intoxication with PQ formulations in the absence and presence of LAS. Gramoxone® and the formulation with LAS were administered by gavage at the doses of 125 mg kg-1 of PQ and 125 mg kg-1 of PQ + 316 mg kg-1 of LAS, respectively. The obtained results showed that LAS improves the safety of PQ formulation by increasing its elimination and preventing lung and kidney injury. LAS prevented the biochemical and histological alterations in lung induced by PQ measured at the end of 24 h and 48 h. This was evidenced by a significant reduction in lipid peroxidation, the maintenance of reduced glutathione levels and decreased levels of oxidized glutathione, as well as the normalization of the urinary biomarkers, creatinine and N-acetyl-β-glucosaminidase. LAS treatment also caused a significant reduction in PQ-induced activation of nuclear factor kappa B (NF-κB) in the lung. The results allow us to conclude that lysine acetylsalicylate improves the safety of PQ formulation in rats by increasing its elimination and preventing lung and kidney injury. This journal is © the Partner Organisations 2014. |
Baltazar, M T; Dinis-Oliveira, R J; Martins, A; Bastos, M D L; Duarte, J A; Guilhermino, L; Carvalho, F Aquatic Toxicology, 146 , pp. 137-143, 2014, (cited By 8). @article{Baltazar2014137b, title = {Lysine acetylsalicylate increases the safety of a paraquat formulation to freshwater primary producers: A case study with the microalga chlorella vulgaris}, author = {M T Baltazar and R J Dinis-Oliveira and A Martins and M D L Bastos and J A Duarte and L Guilhermino and F Carvalho}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84888784605&doi=10.1016%2fj.aquatox.2013.10.034&partnerID=40&md5=59d6b13937c7c7c997d5c773592227e8}, doi = {10.1016/j.aquatox.2013.10.034}, year = {2014}, date = {2014-01-01}, journal = {Aquatic Toxicology}, volume = {146}, pages = {137-143}, abstract = {Large amounts of herbicides are presently used in the industrialized nations worldwide, with an inexorable burden to the environment, especially to aquatic ecosystems. Primary producers such as microalgae are of especial concern because they are vital for the input of energy into the ecosystem and for the maintenance of oxygen in water on which most of other marine life forms depend on. The herbicide paraquat (PQ) is known to cause inhibition of photosynthesis and irreversible damage to photosynthetic organisms through generation of reactive oxygen species in a light-dependent manner. Previous studies have led to the development of a new formulation of PQ containing lysine acetylsalicylate (LAS) as an antidote, which was shown to prevent the mammalian toxicity of PQ, while maintaining the herbicidal effect. However, the safety of this formulation to primary producers in relation to commercially available PQ formulations has hitherto not been established. Therefore, the aim of this study was to evaluate the toxicity of the PQ+LAS formulation in comparison with the PQ, using Chlorella vulgaris as a test organism. Effect criterion was the inhibition of microalgal population growth. Following a 96h exposure to increasing concentrations of PQ, C. vulgaris growth was almost completely inhibited, an effect that was significantly prevented by LAS at the proportion used in the formulation (PQ+LAS) 1:2 (mol/mol), while the highest protection was achieved at the proportion of 1:8. In conclusion, the present work demonstrated that the new formulation with PQ+LAS has a reduced toxicity to C. vulgaris when compared to Gramoxone®. © 2013 Elsevier B.V.}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } Large amounts of herbicides are presently used in the industrialized nations worldwide, with an inexorable burden to the environment, especially to aquatic ecosystems. Primary producers such as microalgae are of especial concern because they are vital for the input of energy into the ecosystem and for the maintenance of oxygen in water on which most of other marine life forms depend on. The herbicide paraquat (PQ) is known to cause inhibition of photosynthesis and irreversible damage to photosynthetic organisms through generation of reactive oxygen species in a light-dependent manner. Previous studies have led to the development of a new formulation of PQ containing lysine acetylsalicylate (LAS) as an antidote, which was shown to prevent the mammalian toxicity of PQ, while maintaining the herbicidal effect. However, the safety of this formulation to primary producers in relation to commercially available PQ formulations has hitherto not been established. Therefore, the aim of this study was to evaluate the toxicity of the PQ+LAS formulation in comparison with the PQ, using Chlorella vulgaris as a test organism. Effect criterion was the inhibition of microalgal population growth. Following a 96h exposure to increasing concentrations of PQ, C. vulgaris growth was almost completely inhibited, an effect that was significantly prevented by LAS at the proportion used in the formulation (PQ+LAS) 1:2 (mol/mol), while the highest protection was achieved at the proportion of 1:8. In conclusion, the present work demonstrated that the new formulation with PQ+LAS has a reduced toxicity to C. vulgaris when compared to Gramoxone®. © 2013 Elsevier B.V. |
Lima, Costa S A; Silvestre, R; Barros, D; Cunha, J; Baltazar, M T; Dinis-Oliveira, R J; Cordeiro-da-Silva, A Crucial CD8+ T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis Journal Article Nanomedicine: Nanotechnology, Biology, and Medicine, 10 (5), pp. e1021-e1030, 2014, (cited By 11). @article{CostaLima2014e1021, title = {Crucial CD8+ T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis}, author = {S A Costa Lima and R Silvestre and D Barros and J Cunha and M T Baltazar and R J Dinis-Oliveira and A Cordeiro-da-Silva}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84903548865&doi=10.1016%2fj.nano.2013.12.013&partnerID=40&md5=dcf1567c028df308141bff21ed775d1b}, doi = {10.1016/j.nano.2013.12.013}, year = {2014}, date = {2014-01-01}, journal = {Nanomedicine: Nanotechnology, Biology, and Medicine}, volume = {10}, number = {5}, pages = {e1021-e1030}, abstract = {This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was >90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8+- but not CD4+-T lymphocytes. Overall, we demonstrate a crucial role for CD8+ cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. From the Clinical Editor: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy. © 2014 Elsevier Inc.}, note = {cited By 11}, keywords = {}, pubstate = {published}, tppubtype = {article} } This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was >90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8+- but not CD4+-T lymphocytes. Overall, we demonstrate a crucial role for CD8+ cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. From the Clinical Editor: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy. © 2014 Elsevier Inc. |
Oliveira, A; Carvalho, F; Pinho, P G; Remião, F; Medeiros, R; Dinis-Oliveira, R J Quantification of morphine and its major metabolites M3G and M6G in antemortem and postmortem samples Journal Article Biomedical Chromatography, 28 (9), pp. 1263-1270, 2014, (cited By 5). @article{Oliveira20141263b, title = {Quantification of morphine and its major metabolites M3G and M6G in antemortem and postmortem samples}, author = {A Oliveira and F Carvalho and P G Pinho and F Remião and R Medeiros and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905570766&doi=10.1002%2fbmc.3158&partnerID=40&md5=c7d2a107e839c14e42e6c05fb9624550}, doi = {10.1002/bmc.3158}, year = {2014}, date = {2014-01-01}, journal = {Biomedical Chromatography}, volume = {28}, number = {9}, pages = {1263-1270}, abstract = {Morphine is one of the most effective agents for the control of significant pain, primarily metabolized to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). While M6G is a potent opioid agonist, M3G has no opioid action and seems to have a role in side-effects caused by morphine. In this study, a reversed-phase high-performance liquid chromatographic method with diode-array and electrochemical detection was developed for the simultaneous determination of morphine, M3G and M6G in antemortem and postmortem samples (plasma, whole blood, urine, liver, kidney and brain). Morphine, glucuronides and internal standard were extracted by double solid-phase extraction and the separation was carried out with a Waters Spherisorb® ODS2 reversed-phase column and potassium phosphate buffer (pH=2.2)-acetonitrile containing sodium dodecyl sulfate as the mobile phase. The method proved to be specific with good linearity for all analytes in a calibration range from 1 to 600ng/mL and proved to be accurate and have adequate precision and recovery. Limits of detection in the studied matrices were 0.4-4.5ng/mL for morphine, 2.7-6.1ng/mL for M3G and 0.8-4.4ng/mL for M6G. The proposed method can be successfully applied to quantify morphine and its metabolites in several biological samples, covering the major routes of distribution, metabolism and elimination of morphine. © 2014 John Wiley & Sons, Ltd.}, note = {cited By 5}, keywords = {}, pubstate = {published}, tppubtype = {article} } Morphine is one of the most effective agents for the control of significant pain, primarily metabolized to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). While M6G is a potent opioid agonist, M3G has no opioid action and seems to have a role in side-effects caused by morphine. In this study, a reversed-phase high-performance liquid chromatographic method with diode-array and electrochemical detection was developed for the simultaneous determination of morphine, M3G and M6G in antemortem and postmortem samples (plasma, whole blood, urine, liver, kidney and brain). Morphine, glucuronides and internal standard were extracted by double solid-phase extraction and the separation was carried out with a Waters Spherisorb® ODS2 reversed-phase column and potassium phosphate buffer (pH=2.2)-acetonitrile containing sodium dodecyl sulfate as the mobile phase. The method proved to be specific with good linearity for all analytes in a calibration range from 1 to 600ng/mL and proved to be accurate and have adequate precision and recovery. Limits of detection in the studied matrices were 0.4-4.5ng/mL for morphine, 2.7-6.1ng/mL for M3G and 0.8-4.4ng/mL for M6G. The proposed method can be successfully applied to quantify morphine and its metabolites in several biological samples, covering the major routes of distribution, metabolism and elimination of morphine. © 2014 John Wiley & Sons, Ltd. |
Oliveira, A; Dinis-Oliveira, R J; Nogueira, A; Gonçalves, F; Silva, P; Vieira, C; Silvestre, R; Carvalho, F; Medeiros, R Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception Journal Article Clinical Biochemistry, 47 (13-14), pp. 1209-1213, 2014, (cited By 8). @article{Oliveira20141209c, title = {Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception}, author = {A Oliveira and R J Dinis-Oliveira and A Nogueira and F Gonçalves and P Silva and C Vieira and R Silvestre and F Carvalho and R Medeiros}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84899467319&doi=10.1016%2fj.clinbiochem.2014.04.009&partnerID=40&md5=a829b03e949cc6fc1af4f7e12f321824}, doi = {10.1016/j.clinbiochem.2014.04.009}, year = {2014}, date = {2014-01-01}, journal = {Clinical Biochemistry}, volume = {47}, number = {13-14}, pages = {1209-1213}, abstract = {Objectives: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (. IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/. B/. RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients. Design and methods: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters. Results: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074}, note = {cited By 8}, keywords = {}, pubstate = {published}, tppubtype = {article} } Objectives: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (. IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/. B/. RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients. Design and methods: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters. Results: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074 |
Oliveira, A; Dinis-Oliveira, R J; Nogueira, A; Azevedo, A S; Gonçalves, F; Silva, P; Carvalho, F; Medeiros, R Genetic profile and cancer-related pain: A tale from two outlier cases with bone metastatic disease Journal Article Pain Medicine (United States), 15 (4), pp. 710-712, 2014, (cited By 6). @article{Oliveira2014710b, title = {Genetic profile and cancer-related pain: A tale from two outlier cases with bone metastatic disease}, author = {A Oliveira and R J Dinis-Oliveira and A Nogueira and A S Azevedo and F Gonçalves and P Silva and F Carvalho and R Medeiros}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84898041413&doi=10.1111%2fpme.12314&partnerID=40&md5=089a772eba156b162b4ed72dca9cf650}, doi = {10.1111/pme.12314}, year = {2014}, date = {2014-01-01}, journal = {Pain Medicine (United States)}, volume = {15}, number = {4}, pages = {710-712}, note = {cited By 6}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Rodrigues, V; Laforge, M; Campillo-Gimenez, L; Soundaramourty, C; Correia-de-Oliveira, A; Dinis-Oliveira, R J; Ouaissi, A; Cordeiro-da-Silva, A; Silvestre, R; Estaquier, J Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques Journal Article PLoS Pathogens, 10 (4), 2014, (cited By 16). @article{Rodrigues2014b, title = {Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques}, author = {V Rodrigues and M Laforge and L Campillo-Gimenez and C Soundaramourty and A Correia-de-Oliveira and R J Dinis-Oliveira and A Ouaissi and A Cordeiro-da-Silva and R Silvestre and J Estaquier}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84901321731&doi=10.1371%2fjournal.ppat.1004096&partnerID=40&md5=09506596c2717a281be125519487095e}, doi = {10.1371/journal.ppat.1004096}, year = {2014}, date = {2014-01-01}, journal = {PLoS Pathogens}, volume = {10}, number = {4}, abstract = {Leishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological profiles characterized during acute and chronic phases of infection. Parasite detection in visceral compartments during the acute phase was associated with differentiation of effector memory CD4 T cells and increased levels of Th1 transcripts. At the chronic phase, parasites colonized novel lymphoid niches concomitant with increased expression of IL10. Despite the occurrence of hypergammaglobulinemia, the production of parasite-specific IgG was poor, being confined to the acute phase and positively correlated with the frequency of an activated memory splenic B cell population. We noticed the expansion of a splenic CD4 T cell population expressing CXCR5 and Bcl-6 during acute infection that was associated with the differentiation of the activated memory B cell population. Moreover, the number of splenic germinal centers peaked at one month after infection, hence paralleling the production of specific IgG. However, at chronic infection these populations contracted impacting the production of parasite-specific IgG. Our study provides new insights into the immune events taking place in a physiologically relevant host and a mechanistic basis for the inefficient humoral response during VL. © 2014 Rodrigues et al.}, note = {cited By 16}, keywords = {}, pubstate = {published}, tppubtype = {article} } Leishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological profiles characterized during acute and chronic phases of infection. Parasite detection in visceral compartments during the acute phase was associated with differentiation of effector memory CD4 T cells and increased levels of Th1 transcripts. At the chronic phase, parasites colonized novel lymphoid niches concomitant with increased expression of IL10. Despite the occurrence of hypergammaglobulinemia, the production of parasite-specific IgG was poor, being confined to the acute phase and positively correlated with the frequency of an activated memory splenic B cell population. We noticed the expansion of a splenic CD4 T cell population expressing CXCR5 and Bcl-6 during acute infection that was associated with the differentiation of the activated memory B cell population. Moreover, the number of splenic germinal centers peaked at one month after infection, hence paralleling the production of specific IgG. However, at chronic infection these populations contracted impacting the production of parasite-specific IgG. Our study provides new insights into the immune events taking place in a physiologically relevant host and a mechanistic basis for the inefficient humoral response during VL. © 2014 Rodrigues et al. |
Rossato, L G; Costa, V M; Dallegrave, E; Arbo, M; Silva, R; Ferreira, R; Amado, F; Dinis-Oliveira, R J; Duarte, J A; Bastos, De Lourdes M; Palmeira, C; Remião, F Mitochondrial cumulative damage induced by mitoxantrone: Late onset cardiac energetic impairment Journal Article Cardiovascular Toxicology, 14 (1), pp. 30-40, 2014, (cited By 17). @article{Rossato201430b, title = {Mitochondrial cumulative damage induced by mitoxantrone: Late onset cardiac energetic impairment}, author = {L G Rossato and V M Costa and E Dallegrave and M Arbo and R Silva and R Ferreira and F Amado and R J Dinis-Oliveira and J A Duarte and M De Lourdes Bastos and C Palmeira and F Remião}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84895821912&doi=10.1007%2fs12012-013-9230-2&partnerID=40&md5=852423554938711bc111c26060e05733}, doi = {10.1007/s12012-013-9230-2}, year = {2014}, date = {2014-01-01}, journal = {Cardiovascular Toxicology}, volume = {14}, number = {1}, pages = {30-40}, abstract = {Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX-induced cardiotoxicity, namely the effects toward mitochondria using in vivo and in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate the early MTX cardiac toxic effects, while the other was euthanized on day 48 (MTX48), to allow the evaluation of MTX late cardiac effects. Cardiac mitochondria isolated from 4 adult untreated rats were also used to evaluate in vitro the MTX (10 nM, 100 nM, and 1 μM) direct effects upon mitochondria functionality. Two rats of MTX48 died on day 35, and MTX treatment caused a reduction in relative body weight gain in both treated groups with no significant changes in water and food intake. Decreased levels of plasma total creatine kinase and CK-MB were detected in the MTX22 group, and increased plasma levels of lactate were seen in MTX48. Increased cardiac relative mass and microscopic changes were evident in both treated groups. Considering mitochondrial effects, for the first time, it was evidenced that MTX induced an increase in the complex IV and complex V activities in MTX22 group, while a decrease in the complex V activity was accompanied by the reduction in ATP content in the MTX48 rats. No alterations in mitochondria transmembrane potential were found in isolated mitochondria from MTX48 rats or in isolated mitochondria directly incubated with MTX. This study highlights the relevance of the cumulative MTX-induced in vivo mitochondriopathy to the MTX cardiotoxicity. © 2013 Springer Science+Business Media New York.}, note = {cited By 17}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX-induced cardiotoxicity, namely the effects toward mitochondria using in vivo and in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate the early MTX cardiac toxic effects, while the other was euthanized on day 48 (MTX48), to allow the evaluation of MTX late cardiac effects. Cardiac mitochondria isolated from 4 adult untreated rats were also used to evaluate in vitro the MTX (10 nM, 100 nM, and 1 μM) direct effects upon mitochondria functionality. Two rats of MTX48 died on day 35, and MTX treatment caused a reduction in relative body weight gain in both treated groups with no significant changes in water and food intake. Decreased levels of plasma total creatine kinase and CK-MB were detected in the MTX22 group, and increased plasma levels of lactate were seen in MTX48. Increased cardiac relative mass and microscopic changes were evident in both treated groups. Considering mitochondrial effects, for the first time, it was evidenced that MTX induced an increase in the complex IV and complex V activities in MTX22 group, while a decrease in the complex V activity was accompanied by the reduction in ATP content in the MTX48 rats. No alterations in mitochondria transmembrane potential were found in isolated mitochondria from MTX48 rats or in isolated mitochondria directly incubated with MTX. This study highlights the relevance of the cumulative MTX-induced in vivo mitochondriopathy to the MTX cardiotoxicity. © 2013 Springer Science+Business Media New York. |
2013 |
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 168 (1), pp. 44-45, 2013, (cited By 17). @article{Baltazar201344, 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}, 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 17}, 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. |
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 217 (1), pp. 34-41, 2013, (cited By 11). @article{Silva201334, 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}, 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 11}, 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. |
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 8 (2), 2013, (cited By 40). @article{Sampaio-Silva2013, 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}, 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 40}, 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. |
Dinis-Oliveira, R J; Magalhães, T Children Intoxications: What is Abuse and What is Not Abuse Journal Article 14 (2), pp. 113-132, 2013, (cited By 7). @article{Dinis-Oliveira2013113, 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}, 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. |
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 69 (4), pp. 553-558, 2013, (cited By 7). @article{Baltazar2013553, 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}, 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 7}, 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. |
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 5 (8), pp. 895-914, 2013, (cited By 34). @article{Barbosa2013895, 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}, 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 34}, 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. |
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 8 (6), 2013, (cited By 0). @article{Sampaio-Silva2013b, 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}, volume = {8}, number = {6}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Magalhães, T; Santos, A; Dinis-Oliveira, R J Forensic medicine: A forgotten world of opportunities and challenges for research Journal Article 44 (6), pp. 479-481, 2013, (cited By 2). @article{Magalhães2013479, title = {Forensic medicine: A forgotten world of opportunities and challenges for research}, author = {T Magalhães and A Santos and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885153436&doi=10.1016%2fj.arcmed.2013.08.001&partnerID=40&md5=ef5666551db09bcb0ef8cae2759e5a59}, doi = {10.1016/j.arcmed.2013.08.001}, year = {2013}, date = {2013-01-01}, volume = {44}, number = {6}, pages = {479-481}, abstract = {Forensic medicine deals with a wide variety of cases. To accomplish the main objectives, this professional field needs to adopt and apply findings from other sciences, namely, different medical specialties and other forensic sciences. The opposite is not yet entirely true due to the fact that forensic medicine deals with cases that are very far away from other medical and scientific interests. It is obvious that this forgotten world of forensic medicine ... is also a new world of opportunities and challenges to research in all scientific areas. © 2013 IMSS.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Forensic medicine deals with a wide variety of cases. To accomplish the main objectives, this professional field needs to adopt and apply findings from other sciences, namely, different medical specialties and other forensic sciences. The opposite is not yet entirely true due to the fact that forensic medicine deals with cases that are very far away from other medical and scientific interests. It is obvious that this forgotten world of forensic medicine ... is also a new world of opportunities and challenges to research in all scientific areas. © 2013 IMSS. |
Pinho, S; Oliveira, A; Costa, I; Gouveia, C A; Carvalho, F; Moreira, R F; Dinis-Oliveira, R J Simultaneous quantification of tramadol and O-desmethyltramadol in hair samples by gas chromatography-electron impact/mass spectrometry Journal Article 27 (8), pp. 1003-1011, 2013, (cited By 16). @article{Pinho20131003, title = {Simultaneous quantification of tramadol and O-desmethyltramadol in hair samples by gas chromatography-electron impact/mass spectrometry}, author = {S Pinho and A Oliveira and I Costa and C A Gouveia and F Carvalho and R F Moreira and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84880268506&doi=10.1002%2fbmc.2894&partnerID=40&md5=a62e093bd858cd3df7a41ce7b3155746}, doi = {10.1002/bmc.2894}, year = {2013}, date = {2013-01-01}, volume = {27}, number = {8}, pages = {1003-1011}, abstract = {Over recent years, hair has become the ideal matrix for retrospective investigation of chronic abuse, including for tramadol. However, in order to exclude the possibility of external contamination, it is also important to quantify simultaneously its main metabolite, O-desmethyltramadol (M1), which presence in hair reflects systemic exposure. In the present study a methodology aimed at the simultaneous quantification of tramadol and M1 in human hair was developed and validated for the first time. After decontamination of hair samples (60mg), tramadol and M1 were extracted with methanol in an ultrasonic bath (~5h). Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. Subsequently to derivatization, analysis was performed by gas chromatography-electron impact/mass spectrometry (GC-EI/MS). The method proved to be selective. The regression analysis for both analytes was shown to be linear in the range of 0.1-20.0ng/mg with correlation coefficients of 0.9995 and 0.9997 for tramadol and M1, respectively. The coefficients of variation oscillated between 3.85 and 13.24%. The limits of detection were 0.03 and 0.02ng/mg, and the lower limits of quantification were 0.08 and 0.06ng/mg for tramadol and M1, respectively. The proof of applicability was performed in hair samples from six patients undergoing tramadol therapy. All samples were positive for tramadol and M1. © 2013 John Wiley & Sons, Ltd.}, note = {cited By 16}, keywords = {}, pubstate = {published}, tppubtype = {article} } Over recent years, hair has become the ideal matrix for retrospective investigation of chronic abuse, including for tramadol. However, in order to exclude the possibility of external contamination, it is also important to quantify simultaneously its main metabolite, O-desmethyltramadol (M1), which presence in hair reflects systemic exposure. In the present study a methodology aimed at the simultaneous quantification of tramadol and M1 in human hair was developed and validated for the first time. After decontamination of hair samples (60mg), tramadol and M1 were extracted with methanol in an ultrasonic bath (~5h). Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. Subsequently to derivatization, analysis was performed by gas chromatography-electron impact/mass spectrometry (GC-EI/MS). The method proved to be selective. The regression analysis for both analytes was shown to be linear in the range of 0.1-20.0ng/mg with correlation coefficients of 0.9995 and 0.9997 for tramadol and M1, respectively. The coefficients of variation oscillated between 3.85 and 13.24%. The limits of detection were 0.03 and 0.02ng/mg, and the lower limits of quantification were 0.08 and 0.06ng/mg for tramadol and M1, respectively. The proof of applicability was performed in hair samples from six patients undergoing tramadol therapy. All samples were positive for tramadol and M1. © 2013 John Wiley & Sons, Ltd. |
Dinis-Oliveira, R J; Magalhães, T Forensic toxicology in drug-facilitated sexual assault Journal Article 23 (7), pp. 471-478, 2013, (cited By 14). @article{Dinis-Oliveira2013471, title = {Forensic toxicology in drug-facilitated sexual assault}, author = {R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84883387973&doi=10.3109%2f15376516.2013.796034&partnerID=40&md5=c04aa10ba1fb5e3abf4454094e936629}, doi = {10.3109/15376516.2013.796034}, year = {2013}, date = {2013-01-01}, volume = {23}, number = {7}, pages = {471-478}, abstract = {The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say no and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since date rape drugs are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed. © 2013 Informa Healthcare USA, Inc.}, note = {cited By 14}, keywords = {}, pubstate = {published}, tppubtype = {article} } The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say no and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since date rape drugs are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed. © 2013 Informa Healthcare USA, Inc. |
Costa, I; Oliveira, A; de Pinho, P G; Teixeira, H M; Moreira, R; Carvalho, F; Dinis-Oliveira, R J Postmortem Redistribution of Tramadol and O-Desmethyltramadol Journal Article 37 (9), pp. 670-675, 2013, (cited By 12). @article{Costa2013670, title = {Postmortem Redistribution of Tramadol and O-Desmethyltramadol}, author = {I Costa and A Oliveira and P G de Pinho and H M Teixeira and R Moreira and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885721867&doi=10.1093%2fjat%2fbkt084&partnerID=40&md5=bc2a244df3e87e74794e208caa25fc00}, doi = {10.1093/jat/bkt084}, year = {2013}, date = {2013-01-01}, volume = {37}, number = {9}, pages = {670-675}, abstract = {Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its efficacy and safety. Although tramadol induces less adverse effects compared with other opioids, an increased number of documented cases of dependence, abuse, intentional overdose or intoxication have been described. In fatal intoxication, the interpretation of the probable cause of death often relies on the measurement of the tramadol concentration in blood. However, postmortem redistribution (PMR) may affect the results and therefore bias the autopsy report. In the present study, the postmortem cardiac and femoral blood samples from 15 cases of fatal tramadol intoxication were obtained to assess the PMR of tramadol and its main active metabolite, O-desmethyltramadol (M1). Toxicological analysis was performed by the gas chromatography- electron impact-mass spectrometry (GC-EI-MS) method, previously developed and validated for the quantification of both analytes. The cardiac-to-femoral blood ratios of 1.40 and 1.28 were obtained for tramadol and M1, respectively. Results were compared with those in the literature and it was possible to conclude that femoral blood should be considered for quantitative interpretations in fatal cases of tramadol intoxication. © The Author [2013]. Published by Oxford University Press. All rights reserved.}, note = {cited By 12}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its efficacy and safety. Although tramadol induces less adverse effects compared with other opioids, an increased number of documented cases of dependence, abuse, intentional overdose or intoxication have been described. In fatal intoxication, the interpretation of the probable cause of death often relies on the measurement of the tramadol concentration in blood. However, postmortem redistribution (PMR) may affect the results and therefore bias the autopsy report. In the present study, the postmortem cardiac and femoral blood samples from 15 cases of fatal tramadol intoxication were obtained to assess the PMR of tramadol and its main active metabolite, O-desmethyltramadol (M1). Toxicological analysis was performed by the gas chromatography- electron impact-mass spectrometry (GC-EI-MS) method, previously developed and validated for the quantification of both analytes. The cardiac-to-femoral blood ratios of 1.40 and 1.28 were obtained for tramadol and M1, respectively. Results were compared with those in the literature and it was possible to conclude that femoral blood should be considered for quantitative interpretations in fatal cases of tramadol intoxication. © The Author [2013]. Published by Oxford University Press. All rights reserved. |
Costa, I; Oliveira, A; de Pinho, P G; Teixeira, H M; Moreira, R; Carvalho, F; Dinis-Oliveira, R J Postmortem Redistribution of Tramadol and O-Desmethyltramadol Journal Article Journal of Analytical Toxicology, 37 (9), pp. 670-675, 2013, (cited By 16). @article{Costa2013670b, title = {Postmortem Redistribution of Tramadol and O-Desmethyltramadol}, author = {I Costa and A Oliveira and P G de Pinho and H M Teixeira and R Moreira and F Carvalho and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885721867&doi=10.1093%2fjat%2fbkt084&partnerID=40&md5=bc2a244df3e87e74794e208caa25fc00}, doi = {10.1093/jat/bkt084}, year = {2013}, date = {2013-01-01}, journal = {Journal of Analytical Toxicology}, volume = {37}, number = {9}, pages = {670-675}, abstract = {Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its efficacy and safety. Although tramadol induces less adverse effects compared with other opioids, an increased number of documented cases of dependence, abuse, intentional overdose or intoxication have been described. In fatal intoxication, the interpretation of the probable cause of death often relies on the measurement of the tramadol concentration in blood. However, postmortem redistribution (PMR) may affect the results and therefore bias the autopsy report. In the present study, the postmortem cardiac and femoral blood samples from 15 cases of fatal tramadol intoxication were obtained to assess the PMR of tramadol and its main active metabolite, O-desmethyltramadol (M1). Toxicological analysis was performed by the gas chromatography- electron impact-mass spectrometry (GC-EI-MS) method, previously developed and validated for the quantification of both analytes. The cardiac-to-femoral blood ratios of 1.40 and 1.28 were obtained for tramadol and M1, respectively. Results were compared with those in the literature and it was possible to conclude that femoral blood should be considered for quantitative interpretations in fatal cases of tramadol intoxication. © The Author [2013]. Published by Oxford University Press. All rights reserved.}, note = {cited By 16}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its efficacy and safety. Although tramadol induces less adverse effects compared with other opioids, an increased number of documented cases of dependence, abuse, intentional overdose or intoxication have been described. In fatal intoxication, the interpretation of the probable cause of death often relies on the measurement of the tramadol concentration in blood. However, postmortem redistribution (PMR) may affect the results and therefore bias the autopsy report. In the present study, the postmortem cardiac and femoral blood samples from 15 cases of fatal tramadol intoxication were obtained to assess the PMR of tramadol and its main active metabolite, O-desmethyltramadol (M1). Toxicological analysis was performed by the gas chromatography- electron impact-mass spectrometry (GC-EI-MS) method, previously developed and validated for the quantification of both analytes. The cardiac-to-femoral blood ratios of 1.40 and 1.28 were obtained for tramadol and M1, respectively. Results were compared with those in the literature and it was possible to conclude that femoral blood should be considered for quantitative interpretations in fatal cases of tramadol intoxication. © The Author [2013]. Published by Oxford University Press. All rights reserved. |
Dinis-Oliveira, R J; Magalhães, T Forensic toxicology in drug-facilitated sexual assault Journal Article Toxicology Mechanisms and Methods, 23 (7), pp. 471-478, 2013, (cited By 19). @article{Dinis-Oliveira2013471b, title = {Forensic toxicology in drug-facilitated sexual assault}, author = {R J Dinis-Oliveira and T Magalhães}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84883387973&doi=10.3109%2f15376516.2013.796034&partnerID=40&md5=c04aa10ba1fb5e3abf4454094e936629}, doi = {10.3109/15376516.2013.796034}, year = {2013}, date = {2013-01-01}, journal = {Toxicology Mechanisms and Methods}, volume = {23}, number = {7}, pages = {471-478}, abstract = {The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say no and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since date rape drugs are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed. © 2013 Informa Healthcare USA, Inc.}, note = {cited By 19}, keywords = {}, pubstate = {published}, tppubtype = {article} } The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say no and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since date rape drugs are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed. © 2013 Informa Healthcare USA, Inc. |
Magalhães, T; Santos, A; Dinis-Oliveira, R J Forensic medicine: A forgotten world of opportunities and challenges for research Journal Article Archives of Medical Research, 44 (6), pp. 479-481, 2013, (cited By 2). @article{Magalhães2013479b, title = {Forensic medicine: A forgotten world of opportunities and challenges for research}, author = {T Magalhães and A Santos and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885153436&doi=10.1016%2fj.arcmed.2013.08.001&partnerID=40&md5=ef5666551db09bcb0ef8cae2759e5a59}, doi = {10.1016/j.arcmed.2013.08.001}, year = {2013}, date = {2013-01-01}, journal = {Archives of Medical Research}, volume = {44}, number = {6}, pages = {479-481}, abstract = {Forensic medicine deals with a wide variety of cases. To accomplish the main objectives, this professional field needs to adopt and apply findings from other sciences, namely, different medical specialties and other forensic sciences. The opposite is not yet entirely true due to the fact that forensic medicine deals with cases that are very far away from other medical and scientific interests. It is obvious that this forgotten world of forensic medicine ... is also a new world of opportunities and challenges to research in all scientific areas. © 2013 IMSS.}, note = {cited By 2}, keywords = {}, pubstate = {published}, tppubtype = {article} } Forensic medicine deals with a wide variety of cases. To accomplish the main objectives, this professional field needs to adopt and apply findings from other sciences, namely, different medical specialties and other forensic sciences. The opposite is not yet entirely true due to the fact that forensic medicine deals with cases that are very far away from other medical and scientific interests. It is obvious that this forgotten world of forensic medicine ... is also a new world of opportunities and challenges to research in all scientific areas. © 2013 IMSS. |
Pinho, S; Oliveira, A; Costa, I; Gouveia, C A; Carvalho, F; Moreira, R F; Dinis-Oliveira, R J Simultaneous quantification of tramadol and O-desmethyltramadol in hair samples by gas chromatography-electron impact/mass spectrometry Journal Article Biomedical Chromatography, 27 (8), pp. 1003-1011, 2013, (cited By 22). @article{Pinho20131003b, title = {Simultaneous quantification of tramadol and O-desmethyltramadol in hair samples by gas chromatography-electron impact/mass spectrometry}, author = {S Pinho and A Oliveira and I Costa and C A Gouveia and F Carvalho and R F Moreira and R J Dinis-Oliveira}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84880268506&doi=10.1002%2fbmc.2894&partnerID=40&md5=a62e093bd858cd3df7a41ce7b3155746}, doi = {10.1002/bmc.2894}, year = {2013}, date = {2013-01-01}, journal = {Biomedical Chromatography}, volume = {27}, number = {8}, pages = {1003-1011}, abstract = {Over recent years, hair has become the ideal matrix for retrospective investigation of chronic abuse, including for tramadol. However, in order to exclude the possibility of external contamination, it is also important to quantify simultaneously its main metabolite, O-desmethyltramadol (M1), which presence in hair reflects systemic exposure. In the present study a methodology aimed at the simultaneous quantification of tramadol and M1 in human hair was developed and validated for the first time. After decontamination of hair samples (60mg), tramadol and M1 were extracted with methanol in an ultrasonic bath (~5h). Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. Subsequently to derivatization, analysis was performed by gas chromatography-electron impact/mass spectrometry (GC-EI/MS). The method proved to be selective. The regression analysis for both analytes was shown to be linear in the range of 0.1-20.0ng/mg with correlation coefficients of 0.9995 and 0.9997 for tramadol and M1, respectively. The coefficients of variation oscillated between 3.85 and 13.24%. The limits of detection were 0.03 and 0.02ng/mg, and the lower limits of quantification were 0.08 and 0.06ng/mg for tramadol and M1, respectively. The proof of applicability was performed in hair samples from six patients undergoing tramadol therapy. All samples were positive for tramadol and M1. © 2013 John Wiley & Sons, Ltd.}, note = {cited By 22}, keywords = {}, pubstate = {published}, tppubtype = {article} } Over recent years, hair has become the ideal matrix for retrospective investigation of chronic abuse, including for tramadol. However, in order to exclude the possibility of external contamination, it is also important to quantify simultaneously its main metabolite, O-desmethyltramadol (M1), which presence in hair reflects systemic exposure. In the present study a methodology aimed at the simultaneous quantification of tramadol and M1 in human hair was developed and validated for the first time. After decontamination of hair samples (60mg), tramadol and M1 were extracted with methanol in an ultrasonic bath (~5h). Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. Subsequently to derivatization, analysis was performed by gas chromatography-electron impact/mass spectrometry (GC-EI/MS). The method proved to be selective. The regression analysis for both analytes was shown to be linear in the range of 0.1-20.0ng/mg with correlation coefficients of 0.9995 and 0.9997 for tramadol and M1, respectively. The coefficients of variation oscillated between 3.85 and 13.24%. The limits of detection were 0.03 and 0.02ng/mg, and the lower limits of quantification were 0.08 and 0.06ng/mg for tramadol and M1, respectively. The proof of applicability was performed in hair samples from six patients undergoing tramadol therapy. All samples were positive for tramadol and M1. © 2013 John Wiley & Sons, Ltd. |
Ricardo Dinis-Oliveira
PhD, European PhD, Post-Doc, DSc
Portuguese
Chinese (Simplified)
Danish
Dutch
English
Finnish
French
Galician
German
Greek
Italian
Japanese
Korean
Slovak
Spanish
Swedish
Turkish
Ukrainian