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- Chronic ketamine administration impairs mitochondrial complex I in the rat liverPublication . Venâncio, Carlos; Antunes, Luis; Félix, Luís; Rodrigues, Paula; Summavielle, Teresa; Peixoto, FranciscoKetamine can induce hepatotoxicity which has been suggested to be dependent on mitochondrial impairment. This study investigated the long-term effects of chronic low-dose ketamine on liver mitochondrial function, oxidative stress parameters, liver histology and glycogen content. Adult rats were administered with saline or ketamine (5 or 10 mg/kg) twice a day for a fourteen-day period in order to mimic chronic treatments. Effects between groups were compared ten days after the treatment had ended. Liver mitochondrial function was monitored in isolated mitochondrial extracts through evaluation of respiration parameters and activity of respiratory complexes, as well as oxidative stress, through lipid peroxidation, protein oxidation and superoxide dismutase activity. The hepatic histology and liver glycogen content were also evaluated. Ketamine groups showed a decreased evolution in body weight gains during the treatment period. Ketamine had no effect either on serum liver enzymes or on the oxidative stress parameters of liver mitochondria. Ketamine decreased the hepatic glycogen content, inhibited mitochondrial complex I and oxygen consumption when glutamate–malate substrate was used. These findings reflect a long-term mitochondrial bioenergetic deterioration induced by ketamine, which may explain the increased susceptibility of some patients to its prolonged or repeated use.
- Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladderPublication . Neto, Susana; Quintela Vieira, Ana Filipa; Montezuma, Diana; Costa, Natália R.; Antunes, Luís; Baptista, Tiago; Oliveira, Ana Isabel; Pinho dos Santos Graça, Maria Inês; Rodrigues, Ângelo; Magalhães, José S.; Oliveira, Jorge; Henrique, Rui; Jerónimo, CarmenDeregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets.
- Ketamine alone or combined with midazolam or dexmedetomidine does not affect anxiety-like behaviours and memory in adult Wistar ratsPublication . Magalhães, Ana; Valentim, Ana; Venâncio, Carlos; Pereira, Mariana; Melo, Pedro; Summavielle, Teresa; Antunes, LuisKetamine administration has been associated with controversial behavioural impairments and psychotic episodes. Even though ketamine alone and in combination with midazolam or dexmedetomidine are frequently used in laboratory animals, the side-effects of such protocols are not well known. Therefore, our aim was to evaluate the effects of ketamine alone and in combination with midazolam or dexmedetomidine on emotional reactivity, as well as the effects on learning and memory in adult rats at least 48 h after anaesthesia. The evaluation of the potential influence of 100 mg/kg ketamine administered alone and in combination with midazolam (5 mg/kg), or dexmedetomidine (0.25 mg/kg) on spatial learning and recognition memory was studied in adult Wistar rats using the radial maze as well as object recognition and location tests. The influence of these combinations on emotional reactivity was investigated using the new exploration test and the elevated plus maze. Results showed that ketamine alone or in combination with midazolam or dexmedetomidine affected neither spatial and recognition memory, nor emotional reactivity. These results reinforce the safe clinical use of ketamine and its combinations in rats in a research context since the administration of these anaesthetic combinations did not produce significant changes with regard to spatial and recognition memory or emotional reactivity. Furthermore, these results indicate that the quality of scientific data produced in adult rat neurobehavioural research is not jeopardized by the use of these anaesthetic protocols.
- An investigation of digital skills of therapeutic radiographers/radiation therapists: A european survey of proficiency level and future educational needsPublication . Barbosa, B.; Oliveira, C.; Bravo, I.; Couto, G.; Antunes, L.; McFadden, S.; Hughes, C.; McClure, P.; Rodrigues, J.; Dias, A.G.This study aims to assess the proficiency level of digital skills, the factors influencing that level and the training needs of Therapeutic Radiographers/Radiation Therapists (TR/RTTs), due to the differences in technology availability and accessibility, variations in the regulation and education of TR/RTTs in European countries, and the lack of a digital skills framework. An online survey was distributed to TR/RTTs working in Europe to capture their self assessment of proficiency levels of digital skills when performing their clinical role. Information was also gathered regarding training, work experience and level of information and communication tech nology (ICT) skills. Quantitative measures were analysed using descriptive statistics and correlation between variables, and qualitative responses using thematic analysis. 101 respondents from 13 European countries completed the survey. Digital skills in treatment planning followed by management and research were the least developed skills, while the most developed were transversal digital skills followed by digital skills in treatment delivery. The Radio therapy areas of practice where TR/RTT has experience (e.g. Planning Image, Treatment Planning, Treatment), as well as the level of generic ICT skills (communication, content creation and problem solving), was related to the level of proficiency of TR/RTT digital skills. Greater scope of practice and level of generic ICT were associated with a higher level of TR/RTT digital skills. Thematic analysis allowed the identification of new sub-themes to be included in the training of TR/RTTs. Education and training of TR/RTTs should be improved and adapted to the current needs of digitalisation to avoid differences in digital proficiency levels. Implications for practice: Aligning TR/RTTs’ digital skill sets with emerging digitalisation will improve current practice and ensure the best care to all RT patients.