IINFACTS Institute of Research and Advanced Training in Health science and Technologies

Gandra, Portugal

IINFACTS Institute of Research and Advanced Training in Health science and Technologies

Gandra, Portugal
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Oliveira A.,University of Porto | Oliveira A.,Portuguese Institute of Oncology Porto | Oliveira A.,IINFACTS Institute of Research and Advanced Training in Health science and Technologies | Pinho D.,University of Porto | And 7 more authors.
Life Sciences | Year: 2014

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.


Dinis-Oliveira R.J.,IINFACTS Institute of Research and Advanced Training in Health science and Technologies | Dinis-Oliveira R.J.,University of Porto | Magalhaes T.,University of Porto | Magalhaes T.,National Institute Of Legal Medicine And Forensic Science Ip | And 7 more authors.
Toxicology Mechanisms and Methods | Year: 2014

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.


Baltazar M.T.,University of Porto | Baltazar M.T.,IINFACTS Institute of Research and Advanced Training in Health science and Technologies | Dinis-Oliveira R.J.,University of Porto | Dinis-Oliveira R.J.,IINFACTS Institute of Research and Advanced Training in Health science and Technologies | And 8 more authors.
Aquatic Toxicology | Year: 2014

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.

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