RESUMO
Autism spectrum disorder (ASD) has become one of the most well-known disorders encountered since early childhood among people. Nowadays, the main concerns are its high prevalence and the lack of proper therapeutic interventions. In this way, the necessity of using animal models that can mimic some of the spectrum symptoms, besides deepening the mechanisms of occurrence, is undeniable. Oxytocin (OT) is often mentioned and linked to producing social domain improvements. The goal of the present study was to determine if different time exposures to OT can trigger distinct behavioral responses in zebrafish, potentially offering insights into autism therapy. To accomplish this goal, zebrafish were exposed to the same dose of OT (33.2 ng/mL OT) for one week but with different time frames, such as: continuous exposure for seven days, fifteen minutes per day for seven days, and every two days for the same amount of time. The behavior of the fish was recorded using the EthoVision XT 11.5 software, and each trial lasted four minutes. Specific parameters for locomotor activity and aggressive behavior were measured. Overall, zebrafish exposure to OT generated several improvements in locomotor activity and aggressive behavior. Moreover, the differences in the exposure period indicated that time is an important factor, showing that continuous exposure to OT was linked with better performance than exposure to the hormone every two days. At the same time, the most variable results were observed in the case of fish exposed every day to OT. Exposure to OT could lead to certain improvements in zebrafish behavior that can be time-sensitive. Nevertheless, further work is needed in order to investigate the mechanisms of action of OT in an ASD context.
RESUMO
Background and Objectives: Alcoholic hepatitis (AH) poses a medical challenge, causing moderately severe to life-threatening episodes with high short- and long-term mortality. This study aimed to explore real-world corticosteroid utilization in severe AH, response predictors, and patient outcomes. Materials and Methods: We conducted a retrospective study on patients admitted for severe AH, defined as a Maddrey Discriminant Function score equal to or above 32, at a tertiary care center. We reviewed patients' medical observation charts to identify corticosteroid prescriptions, reasons for ineligibility, and response rates. Responders were defined based on the Lille score, and predictors of non-response were identified. Short-term (one-month) and long-term (one-year) mortality rates were calculated according to treatment and response. Results: Out of 310 patients enrolled with severe AH, 59% received corticosteroids, achieving a response rate of 75.4%. The reasons for not administering corticosteroids were as follows: uncontrolled infections (27.6%), renal dysfunction (20.4%), gastrointestinal bleeding (18.9%), acute pancreatitis (7.1%), uncontrolled diabetes (3.1%), and other or unknown causes (22.8%). The overall 1-month mortality rate was 12.2%, higher in non-responders (35.3%) and patients who did not receive corticosteroids (13.4%) compared to responders (3.6%). The overall 1-year mortality rate was 62.5%, similar between patients who did not receive corticosteroids (78.7%) and non-responders (77.7%) and higher compared to responders (42.8%). Predictive factors for non-response included older age (OR = 1.05, 95%CI: 1.01-1.08), concomitant cirrhosis (OR= 2.11, 95% CI: 1.064-4.20), MELD scores exceeding 30 (OR = 2.42, 95% CI: 1.21-4.80), severe hypoalbuminemia (OR = 2.46, 95%CI: 1.12-5.37), and increased serum creatinine (OR = 1.5, 95% CI: 1.1-2.03). Among the prognostic scores, MELD 3.0 score exhibited superior efficacy for short-term (AUC = 0.734, 95% CI 0.656-0.811) and long-term mortality (AUC = 0.777, 95% CI: 0.724-0.830) compared to alternative scoring systems. Conclusions: Low eligibility rate and poor prognosis underscore the need for effective therapies. Our findings contribute to refining risk stratification and early prediction of non-response, aiding clinicians in identifying more beneficial therapies.
Assuntos
Hepatite Alcoólica , Pancreatite , Humanos , Hepatite Alcoólica/complicações , Hepatite Alcoólica/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Doença Aguda , Prognóstico , Índice de Gravidade de Doença , Corticosteroides/uso terapêuticoRESUMO
Constant exposure to a variety of environmental factors has become increasingly problematic. A variety of illnesses are initiated or aided by the presence of certain perturbing factors. In the case of autism spectrum disorder, the environmental component plays an important part in determining the overall picture. Moreover, the lack of therapies to relieve existing symptoms complicates the fight against this condition. As a result, animal models have been used to make biomedical research easier and more suited for disease investigations. The current study used zebrafish as an animal model to mimic a real-life scenario: acute exposure to an increased dose of pesticides, followed by prospective intervention-based therapy with vitamin B12 (vit. B12). It is known that vit. B12 is involved in brain function nerve tissue, and red blood cell formation. Aside from this, the role of vit. B12 in the redox processes is recognized for its help against free radicals. To investigate the effect of vit. B12, fish were divided into four different groups and exposed to a pesticide mixture (600 µg L-1 fipronil + 600 µg L-1 pyriproxyfen) and 0.24 µg L-1 vit. B12 for 14 days. The impact of the compounds was assessed daily with EthoVision XT 11.5 software for behavioral observations, especially for sociability, quantified by the social interaction test. In addition, at the end of the study, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured. The results showed significant improvements in locomotor activity parameters and a positive influence of the vitamin on sociability. Regarding the state of oxidative stress, high activity was found for SOD and GPx in the case of vit. B12, while fish exposed to the mixture of pesticides and vit. B12 had a lower level of MDA. In conclusion, the study provides new data about the effect of vit. B12 in zebrafish, highlighting the potential use of vitamin supplementation to maintain and support the function of the organism.