Health literacy - study protocol for LiSa cohort study.

BACKGROUND: Health literacy is the degree to which individuals have the ability to find, understand, and use information and services to inform health-related decisions and actions for themselves and others, whether at home, at the workplace, in the community, marketplace, healthcare sector, or the political arena. The main aim of this project is to measure health literacy in the adult population living in the municipality of Leiria over the next 10 years. As secondary objectives it is intended to characterize anxiety and depression, metabolic risk and health behaviors in the same population and over the same period. METHODS: This is a prospective cohort study that collects data on HL, anxiety and depression, health characteristics, health behavior and sociodemographic data. The study population will be composed by adults (≥ 18 years old) who are non-institutionalized and living in private households in Leiria. The random sample is stratified by gender and age groups. A face-to-face interview will be conducted with the Computer Assisted Personal Interview at baseline. Follow-up will be carried out every 2 years via telephone call. The association between independent variables and health literacy is examined by means of variance analysis with measurement repetition, and taking into consideration follow-up. DISCUSSION: The LiSa project is a population-based study, derived from a random sampling technique that will allow the analysis of health outcomes in a representative sample of the population of the municipality of Leiria. The LiSa study will be a valuable resource for epidemiological research, as it will provide fundamental information to improve public health policies regarding health literacy in Portugal. TRIAL REGISTRATION: Clinical trials: NCT05558631 (registered on 26/09/2022).

Noninvasive transcranial brain stimulation in central post-stroke pain: A systematic review.

BACKGROUND: The aim of this systematic review is to analyze the efficacy of noninvasive brain stimulation (NBS) in the treatment of central post-stroke pain (CPSP). METHODS: We included randomized controlled trials testing the efficacy of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation versus placebo or other usual therapy in patients with CPSP. Articles in English, Portuguese, Spanish, Italian, and French were included. A bibliographic search was independently conducted on June 1, 2022, by two authors, using the databases MEDLINE (PubMed), Embase (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science Core Collection. The risk of bias was assessed using the second version of the Cochrane risk of bias (RoB 2) tool and the certainty of the evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation. RESULTS: A total of 2,674 records were identified after removing duplicates, of which 5 eligible studies were included, involving a total of 119 patients. All five studies evaluated repetitive TMS, four of which stimulated the primary motor cortex (M1) and one stimulated the premotor/dorsolateral prefrontal cortex. Only the former one reported a significant pain reduction in the short term, while the latter one was interrupted due to a consistent lack of analgesic effect. CONCLUSION: NBS in the M1 area seems to be effective in reducing short-term pain; however, more high-quality homogeneous studies, with long-term follow-up, are required to determine the efficacy of this treatment in CSPS.

Advancing cortisol measurements in zebrafish: Analytical validation of a commercial ELISA kit for skin mucus cortisol analysis.

Cortisol is the main stress biomarker used for zebrafish. However, zebrafish small size made it challenging to extract cortisol without harming or killing the fish. Thus, researchers adopted a terminal method, the trunk cortisol, as standard practice. Here, we developed and validated an alternative and minimally invasive technique for measuring cortisol in the skin mucus of adult zebrafish, using a commercial enzyme-linked immunosorbent assay (ELISA). For this, AB zebrafish were randomly assigned to a precision, accuracy, and specificity test. Each sample contained the skin mucus of five to ten fish or one fish trunk. The cortisol was extracted using methanol as organic solvent. The results obtained showed an adequate precision (intra-assay coefficient of variation (CV) <15%; inter-assay CV = 26%), accuracy (CV <120%), and specificity (r2 =0.96-0.98) for skin mucus cortisol levels, as well as for trunk cortisol.•A commercial ELISA was analytically validated to measure cortisol in the skin mucus of zebrafish.•Skin mucus cortisol is a non-terminal method that reduce the number of animals used and allows longitudinal studies.

Biological Response Following the Systemic Injection of PEG-PAMAM-Rhodamine Conjugates in Zebrafish.

Numerous therapeutic and diagnostic approaches used within a clinical setting depend on the administration of compounds via systemic delivery. Biomaterials at the nanometer scale, as dendrimers, act as delivery systems by improving cargo bioavailability, circulation time, and the targeting of specific tissues. Although evaluating the efficacy of pharmacological agents based on nanobiomaterials is crucial, conducting toxicological assessments of biomaterials is essential for advancing clinical translation. Here, a zebrafish larvae model was explored to assess the biocompatibility of poly(amido amine) (PAMAM), one of the most exploited dendrimers for drug delivery. We report the impact of a systemic injection of polyethylene glycol (PEG)-modified G4 PAMAM conjugated with rhodamine (Rho) as a mimetic drug (PEG-PAMAM-Rho) on survival, animal development, inflammation, and neurotoxicity. A concentration- and time-dependent effect was observed on mortality, developmental morphology, and innate immune system activation (macrophages). Significant effects in toxicological indicators were reported in the highest tested concentration (50 mg/mL PEG-PAMAM-Rho) as early as 48 h post-injection. Additionally, a lower concentration of PEG-PAMAM-Rho (5 mg/mL) was found to be safe and subsequently tested for neurotoxicity through behavioral assays. In accordance, no significative signs of toxicity were detected. In conclusion, the dose response of the animal was assessed, and the safe dosage for future use in theragnostics was defined. Additionally, new methodologies were established that can be adapted to further studies in toxicology using other nanosystems for systemic delivery.

Behavioral Profiling of Zebrafish (Danio rerio) Larvae: Activity, Anxiety, Avoidance, and Startle Response.

Apart from morphological, biochemical, and genetic alterations induced by teratogen compounds, there is an increased interest in characterizing behavioral alterations. Behavior is a sensitive parameter that can provide information regarding developmental disruptions non-invasively. Behavioral disturbances interfere with animals' capacity to cope with the environment, having an impact on the organism's life. Hereby, behavioral assays consisting of recording larvae in multi-well plates, Petri dishes, or cuvettes and video analysis using adequate software, allowing teratogen screening of behavior, are proposed. Examples of how to evaluate locomotor, anxiety-like and avoidance-like behaviors, and the integrity of sensory-motor functions and learning are discussed in this chapter.

Housing Conditions Affect Adult Zebrafish (Danio rerio) Behavior but Not Their Physiological Status.

Zebrafish is a valuable model for neuroscience research, but the housing conditions to which it is exposed daily may be impairing its welfare status. The use of environmental enrichment and the refinement of methodology for cortisol measurement could reduce stress, improving its welfare and its suitability as an animal model used in stress research. Thus, this study aimed to evaluate (I) the influence of different housing conditions on zebrafish physiology and behavior, and (II) skin mucus potential for cortisol measurement in adult zebrafish. For this, AB zebrafish were raised under barren or enriched (PVC pipes and gravel image) environmental conditions. After 6 months, their behavior was assessed by different behavioral paradigms (shoaling, white-black box test, and novel tank). The physiological response was also evaluated through cortisol levels (whole-body homogenates and skin mucus) and brain oxidative stress markers. The results revealed that enriched-housed fish had an increased nearest neighbors' distance and reduced activity. However, no effect on body length or stress biomarkers was observed; whole-body and skin mucus cortisol levels had the same profile between groups. In conclusion, this study highlights the skin mucus potential as a matrix for cortisol quantification, and how housing conditions could influence the data in future studies.

Anti-Algics in the Therapeutic Response of Breast and Urological Cancers.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Saúde coletiva e psicologia social da práxis: um caminho interdisciplinar como metaformação na pós-graduação / Collective health and social psychology of praxis: an interdisciplinary path for meta-formation in graduate studies

RESUMO Este artigo parte da compreensão de interdisciplinaridade como modo de operar face às visões fragmentadas presentes nos processos de produção e de socialização do conhecimento. Objetiva compartilhar reflexões que problematizam a interdisciplinaridade a partir da experiência de formação acadêmica na pós-graduação de um grupo de pesquisa cujos integrantes expressam diversidade de formação e inserção profissional e se debruçam sobre relações entre políticas públicas, saúde e necessidades das pessoas. As reflexões foram elaboradas com base em questões emergentes nos encontros sistemáticos do grupo, que foi tomado como estratégia teórico-metodológica, e sustentadas a partir do diálogo entre saúde coletiva, como campo de saber e de prática, e psicologia social da práxis, formulada por Enrique Pichon-Rivière. O eixo articulador dessa experiência é a formação em sentido amplo que se manifesta pelo princípio de indissociabilidade ensino-pesquisa-extensão, i.e., aprender-investigar-fazer, e como autoformação em um processo mútuo e de ação reflexiva, de aprender a aprender. Nesse sentido, argumenta-se que é metaformação e só pode se dar na perspectiva de diálogos de saberes e interdisciplinares.

ABSTRACT This article is based on the understanding of interdisciplinarity as a way to act against the fragmented visions present in the processes of knowledge production and socialization. The objective is to share reflections that problematize interdisciplinarity from the experience of graduate academic training in a research group whose members have diverse training and professional fields and focus on the relationships between public policy, health and human needs. The reflections were based on issues that emerged during the group's systematic meetings, and the group was understood as a theoretical and methodological strategy, and was sustained by the dialogue between collective health as a field of knowledge and practice, and the social psychology of praxis, formulated by Enrique Pichon-Rivière. The articulating axis of this experience is training in its broadest sense, manifested on the principle of the inseparability of (i.e., learning-research-doing) and as self-training in a mutual process of reflective teaching-research-outreach action, of learning how to learn. In this sense, it is argued that it is a metatraining that can only take place from the perspective of knowledge dialogues and interdisciplinarity.

Behavioural Aversion and Cortisol Level Assessment When Adult Zebrafish Are Exposed to Different Anaesthetics.

The use of zebrafish (Danio rerio) as an animal model is growing and occurs in a wide range of scientific areas. Therefore, researchers need better and more appropriate anaesthetics for stressful and/or painful procedures to prevent unpleasant experiences. Thus, we aimed to study if adult zebrafish displayed aversion-associated behaviours (conditioned place aversion) and alterations in cortisol levels when exposed to equipotent concentrations of MS222, propofol/lidocaine, clove oil, or etomidate. Adult AB zebrafish (mixed-sex, N = 177) were randomly assigned to MS222 (150 mg/L), Propofol/Lidocaine (5 mg/L propofol + 150 mg/L lidocaine), Clove Oil (45 mg/L), or Etomidate (2 mg/L) groups. The conditioned place aversion test was used to assess behavioural aversion. Only etomidate resulted in a similar aversion to the positive control group (HCl; pH = 3). Cortisol levels were measured 5 and 15 min after loss of equilibrium. Etomidate induced low levels of cortisol by impairing its synthesis, whereas all the other groups had similar cortisol levels. Based on our data, etomidate was ruled out as an alternative to MS222, as it showed an aversive profile. The remaining protocols were not innocuous, displaying a weak aversive profile when compared to the positive control. In conclusion, a combination of propofol with lidocaine, clove oil, and MS222 were valid candidates for use as anaesthetic protocols.

Anesthesia Overdose Versus Rapid Cooling for Euthanasia of Adult Zebrafish.

The rapid increase in zebrafish use needs to be accompanied by research into the refinement of procedures. The European (EU) Directive lists three possible euthanasia methods for fish: anesthetic overdose, electrical stunning, and concussion. However, for small fish such as zebrafish, concussion and electrical stunning are difficult to perform, leaving anesthetic overdose as the most used method. Our aim was to test the efficacy and side effects of anesthesia overdose using different anesthetics and the rapid cooling method to euthanize adult zebrafish. Adult mixed-sex AB zebrafish were randomly assigned to: 250 mg/L MS222; 20 mg/L propofol +100 mg/L lidocaine; 6 mg/L etomidate; 50 mg/L clove oil; and rapid cooling (water at 2°C-4°C). Two minutes after opercular movement ceased, animals were transferred into clean water for 20 min and recovery assessed, or decapitated and used for biochemical analysis of the gills, muscle, liver, and brain; for the histological analysis of the gills and muscle; or for the assessment of cortisol levels. No animal recovered; rapid cooling was the quickest and etomidate overdose was the slowest method to cease the opercular movements. There were no major differences between euthanasia methods regarding the biochemical or histological data. Cortisol levels were higher in the rapid cooling group, but only when compared with the propofol/lidocaine group. The use of a physical method of euthanasia, such as rapid cooling, is essential when chemicals, such as anesthetics, may interfere with postmortem analyses. Although anesthetic overdose can be used without major effects on the analyses conducted in this work, rapid cooling can be another option with the advantage of being simple to administer, easily available, affordable, and very quick; this decreases the potential duration of suffering, being more humane. Therefore, a change in EU legislation should be considered to include additional humane options for euthanasia, such as rapid cooling, for zebrafish and other small tropical fish.

The Potential Effect of Lidocaine, Ropivacaine, Levobupivacaine and Morphine on Breast Cancer Pre-Clinical Models: A Systematic Review.

Breast cancer (BC) is one of the most common types of cancer and the second leading cause of death in women. Local anaesthetics (LAs) and opioids have been shown to influence cancer progression and metastasis formation in several pre-clinical studies. However, their effects do not seem to promote consensus. A systematic review was conducted using the databases Medline (via PubMed), Scopus, and Web of Science (2010 to December 2021). Search terms included "lidocaine", "ropivacaine", "levobupivacaine", "morphine", "methadone", "breast cancer", "breast carcinoma" and "breast neoplasms" in diverse combinations. The search yielded a total of 784 abstracts for initial review, 23 of which met the inclusion criteria. Here we summarise recent studies on the effect of analgesics and LAs on BC cell lines and animal models and in combination with other treatment regimens. The results suggest that local anaesthetics have anti-tumorigenic properties, hence their clinical application holds therapeutic potential. Regarding morphine, the findings are conflicting, but this opioid appears to be a tumour-promoting agent. Methadone-related results are scarce. Additional research is clearly required to further study the mechanisms underlying the controversial effects of each analgesic or LA to establish the implications upon the outcome and prognosis of BC patients' treatment.

Self-compassion in Acceptance and Commitment Therapy for chronic pain: a pilot study.

OBJECTIVES: Evidence shows that Acceptance and Commitment Therapy (ACT) is an empirically supported psychological approach for chronic pain (CP) management. Although self-compassion is not explicitly a target of ACT, it seems to be one mechanism of change in ACT for CP. However, research is lacking on the benefits of including explicit self-compassionate exercises in ACT for CP. The current study pilot tested a Compassionate ACT 8-session group program (COMP.ACT; n=9), as well as an ACT-only 8-session group program (ACT; n=7), in a sample of women with CP. METHODS: The current study follows a quasi-experimental design, and conducts Reliable and Significant Change analyses comparing pre- to post-intervention scores of self-report measures. RESULTS: No differences were found between conditions at baseline, nor between completers and drop-outs. Although preliminary, results showed COMP.ACT led to greater clinical improvements in depression and anxiety, while ACT led to greater improvements in stress and uncompassionate self-responding. Reliable and Significant Change analysis showed that some participants improved significantly (in psychopathological symptoms, valued living and uncompassionate self-responding) in both conditions, while the majority did not change significantly. CONCLUSIONS: More research is needed to conclude whether explicit self-compassion exercises are useful in ACT for CP. Limitations and implications are further discussed.

MS-222 and Propofol Sedation during and after the Simulated Transport of Nile tilapia (Oreochromis niloticus).

The use of anesthetics has been suggested as a strategy to hamper live fish transport-induced stress. Still, there is insufficient data available on the use of alternative anesthetics to MS-222. This study investigated the use of propofol to mitigate stress in Nile tilapia (Oreochromis niloticus, 143.8 ± 20.9 g and 20.4 ± 0.9 cm) during a 6 h simulated transport. Individuals (n = 7) were divided into three groups: control, 40 mg L-1 MS-222, and 0.8 mg L-1 propofol. A naïve group non-transported was also considered. During the 6 h transport and 24 h after, the response to external stimuli, opercular movements, water quality parameters, behavior, blood hematology and other physiological values, the histopathology of the gills, the quality of the fillet, and oxidative-stress changes in gills, muscle, brain, and liver were evaluated. Propofol increased swimming activity of fish but decreased opercular movements and responses to external stimuli, indicating oscillations of the sedation depth. Water pH and glucose levels increased, while hematocrit (HCT) and lactate decreased in propofol groups at 6 h. At this time-point, MS-222 also induced a decrease in the HCT and lactate levels while increasing cortisol levels. Despite these effects, the stress-related behaviors lessened with anesthetics compared to the control group. After the recovery period, physiological responses normalized in animals from both anesthetic groups, but the control still had high cortisol levels. Overall, propofol is a good alternative for the transportation of this species, showing efficient sedation without compromising health or fillet quality. However, further pharmacodynamics and pharmacokinetics knowledge is required to support its use in aquaculture settings.

Adult Zebrafish Anesthesia: A Study of Efficacy and Behavioral Recovery of Different Anesthetics.

The use of proper anesthesia in zebrafish research is essential to ensure fish welfare and data reliability. However, anesthesia long-term side effects remain poorly understood. The purpose of this study was to assess anesthesia quality and recovery in adult zebrafish using different anesthetic protocols and to determine possible long-term effects on the fish activity and anxiety-like behaviors after anesthesia. Mixed-sex adult AB zebrafish were randomly assigned to five different groups (Control, 175 mg/L of tricaine methanesulfonate [MS222], 45 mg/L of clove oil, 2 mg/L of etomidate, and 5 mg/L of propofol combined with 150 mg/L of lidocaine) and placed in the respective anesthetic bath. Time to lose the equilibrium, response to touch and to caudal fin pinch stimuli, and recovery after anesthesia administration were evaluated. In addition, after stopping anesthesia, respiratory rate, activity, and anxiety-like behaviors in the novel tank test were studied. Overall, all protocols proved to be adequate for zebrafish anesthesia research as they showed full recovery at 1 h, and only etomidate had minor effects on fish behavior in the novel tank, a validated test for anxiety.

A Systematic Review of Self-Compassion in Chronic Pain: From Correlation to Efficacy.

Chronic pain (CP) is a common condition affecting millions of people worldwide. Compassion-related interventions are proving to be advantageous in CP, and self-compassion (SC) is hypothesized to be related with pain regulation physiological processes, as well as with psychological benefits in CP. We aimed to review scientific literature on: 1) Compassion-based psychological interventions and their changes in pain outcomes; and 2) associations between SC and pain-related outcomes. We performed a systematic research in four electronic databases: MEDLINE, EMBASE, PsycINFO and the Cochrane Library from inception until April 2020. In Question 1, we included studies involving adult patients with CP who participated in compassion-based psychological interventions. In Question 2, we included studies that examined the associations between SC and pain outcomes in adults with CP. We identified 16 studies. For Question 1, we included seven studies focused on different compassion-based interventions that assessed at least one pain outcome, in a total of 253 participants with CP associated with multiple conditions. For Question 2, we included nine studies, in a total of 1,430 participants, with eight different pain outcomes: Intensity, acceptance, catastrophizing, self-efficacy, disability, distress, pain related coping and anxiety. Considering the high heterogeneity between studies and the poor-quality assessment, we could not draw definitive conclusions on the efficacy of compassion-based interventions nor on the association between SC and pain outcomes. Studies are further discussed in detail. This review can be a starting point for large-scale and high-quality trials in this area as it provides an organized overview of the current literature on this topic.

Malformations and mortality in zebrafish early stages associated with elevated caspase activity after 24 h exposure to MS-222.

Tricaine methanesulfonate (MS-222) is a commonly used anaesthetic agent for immobilization of aquatic species. However, delayed development and malformations have been observed in 24 hpf (hours post-fertilization) zebrafish embryos after long-term immobilization. Still, no comprehensive study has been described regarding zebrafish exposure to MS-222 during the first hours of development, which are one of the most sensitive life stages to toxicants. Therefore, this research aimed to assess the toxicity of a 24 h exposure to MS-222 on zebrafish embryonic development. Based on the MS-222 LC50, early blastula stage embryos (~2 hpf) were exposed to 0, 12.5, 25 and 50 mg L-1 for 24 h and then allowed to develop up to 144 hpf. The chromatographic analysis showed that this anaesthetic agent bioaccumulates in 26 hpf zebrafish larvae in a concentration-dependent manner. In addition, increased mortalities and skeletal abnormalities were observed at 144 hpf, namely in the highest tested concentration. Yet, no craniofacial anomalies were observed either by alcian blue or calcein staining methods. Independently of the tested concentration, decreased speed and distance travelled were perceived in 144 hpf larvae. At the biochemical level, decreased in vivo reactive oxygen species (ROS) generation and apoptosis was observed. Additionally, catalase activity was increased at 26 hpf while results of mRNA expression showed a decreased gclc transcript content at the same time-point. Overall, data obtained highlight the toxicological risk of MS-222 and support ROS-mediated cell death signalling changes through the elevation of catalase activity as an adaptative or protective response.

Above and beyond emotional suffering: the unique contribution of compassionate and uncompassionate self-responding in chronic pain.

Objectives Studies have shown that self-compassion plays a protective role against depression in women with chronic pain (CP). However, the majority of studies in CP have used the total score of the self-compassion scale (SCS), which have raised concerns due to potential overlap, not only between the uncompassionate self-responding factors and psychopathology, but also between self-compassion as a whole and other well-known psychological processes (e.g., mindfulness, acceptance, psychological flexibility). This calls for a more nuanced understanding of which components of (un)compassionate self-responding adds to better mental health in CP. Methods This study explores the unique contribution of compassionate and uncompassionate self-responding to depressive symptoms in women with CP undergoing pain consultation (n = 49). Results Correlation analyses suggest that compassionate self-responding only significantly correlates with progress in valued living, while the uncompassionate self-responding significantly correlates with pain fusion, pain avoidance, obstructions to valued living and depression. Multiple regression analysis showed that self-compassion contributes to depressive symptoms (R2 = 8%) above and beyond pain intensity and disability (R2 = 12%) and psychological (in) flexibility processes (R2 = 31%), and uncompassionate (but not compassionate) self-responding uniquely contributes to depressive symptoms (sr 2  = 18%). Conclusions Findings suggest that uncompassionate self-responding is a stronger contributor to depression in CP than compassionate self-responding. Clinical implications are further discussed.

MS-222 induces biochemical and transcriptional changes related to oxidative stress, cell proliferation and apoptosis in zebrafish embryos.

MS-222, the most widely used anaesthetic in fish, has been shown to induce embryotoxic effects in zebrafish. However, the underlying molecular effects are still elusive. This study aimed to investigate the effects of MS-222 exposure during early developmental stages by evaluating biochemical and molecular changes. Embryos were exposed to 50, 100 or 150 mg L-1 MS-222 for 20 min at one of three developmental stages (256-cell, 50% epiboly, or 1-4 somite stage) and oxidative-stress, cell proliferation and apoptosis-related parameters were determined at two time-points (8 and 26 hpf). Following exposure during the 256-cell stage, the biochemical redox balance was not affected. The genes associated with glutathione homeostasis (gstpi and gclc) were affected at 8 hpf, while genes associated with apoptosis (casp3a and casp6) and cellular proliferation (pcna) were found affected at 26 hpf. An inverted U-shaped response was observed at 8 hpf for catalase activity. After exposure at the 50% epiboly stage, the gclc gene associated with oxidative stress was found upregulated at 8 hpf, while gstpi was downregulated and casp6 was upregulated later on, coinciding with a decrease in glutathione peroxidase (GPx) activity and a non-monotonic elevation of protein carbonyls and casp3a. Additionally, MS-222 treated embryos showed a decrease in DCF-staining at 26 hpf. When exposure was performed at the 1-4 somite stage, a similar DCF-staining pattern was observed. The activity of GPx was also affected whereas RT-qPCR showed that caspase transcripts were dose-dependently increased (casp3a, casp6 and casp9). The pcna mRNA levels were also found to be upregulated while gclc was changed by MS-222. These results highlight the impact of MS-222 on zebrafish embryo development and its interference with the antioxidant, cell proliferation and cellular death systems by mechanisms still to be explained; however, the outcomes point to the Erk/Nrf2 signalling pathway as a target candidate.

Review on the use of zebrafish embryos to study the effects of anesthetics during early development.

Over the years, the potential toxicity of anesthetics has raised serious concerns about its safe use during pregnancy. As evidence emerged from research in animal models, showing that some anesthetic drugs are potential teratogenic, the determination of the risk of exposures to anesthetic drugs at early life stages became mandatory. However, due to inaccessibility and ethical constrains related to experimental conditions, the use of early life stages in mammalian models is limited. In this regard, some animal and nonanimal models have been suggested to surpass mammalian use in experimentation. Among them, the zebrafish embryo test has been recognized as a promising alternative in toxicology research, as well as an inexpensive and practical test. Substantial information collected from developmental research following compounds exposure, has contributed to the application of zebrafish assays in research, although only a few studies have focused on the use of early life stages of zebrafish to evaluate the developmental effects of anesthetics. Based on the recent advances of science and technology, there is a clear potential for zebrafish early life stages to provide new insights into anesthetics teratogenicity. This review provides an overview of recent anesthesia research using zebrafish embryos, demonstrating its usefulness to the anesthesia field, discussing the recent findings on various aspects related to the effects of anesthetics during early life development and the strengths and limitations of this model system.