Real-World Utilization of Corticosteroids in Severe Alcoholic Hepatitis: Eligibility, Response, and Outcomes.

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.

Coagulation Dysfunctions in Non-Alcoholic Fatty Liver Disease-Oxidative Stress and Inflammation Relevance.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.

Relationship between Vitamin Deficiencies and Co-Occurring Symptoms in Autism Spectrum Disorder.

Recently, connections have been made between feeding and eating problems and autism spectrum disorder (ASD) and between autism pathophysiology and diet issues. These could explain some of the mechanisms which have not yet been discovered or are not sufficiently characterized. Moreover, there is an increased awareness for micronutrients in ASD due to the presence of gastrointestinal (GI) problems that can be related to feeding issues. For example, levels of vitamins B1, B6, B12, A and D are often reported to be low in ASD children. Thus, in the present mini review we focused on describing the impact of some vitamins deficiencies and their relevance in ASD patients.

Toxicity and chronic effects of deltamethrin exposure on zebrafish (Danio rerio) as a reference model for freshwater fish community.

In this study zebrafish specimens were exposed for 15 days to 0.25, 0.5, 1 and 2 µg L-1 non-lethal concentrations of deltamethrin (DM) knowing that is the active compound in insecticides used on agricultural crops. They were investigated important issues resulted during the chronic exposure with DM: effects on aggressive behavior and swimming performances knowing that is a high neurotoxic compound; toxicity on nervous system investigated on telencephalon, optic tectum and cerebellum; activity of PCNA, p53 and TUNEL as toxicity markers in immunocytochemistry of the histological samples; changes of elements concentrations in the fish body and their role in detoxification of DM. This scenario investigated the harmful effects of this compound for freshwater fish communities. The aggressive behavior significantly increased and remained constant for the concentration 0.5 µg L-1. They were not evidences in changing of anxiety level and swimming performances. The nervous system suffered significant damage for all studied concentrations and confirmed the changes in the behavior. Selenium concentration in the body decreased and may be involved in the detoxification processes.

Oxytocin Enhances Time-Dependent Responses in the Aggressive Zebrafish (Danio rerio).

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.

Vitamin B12 Ameliorates Pesticide-Induced Sociability Impairment in Zebrafish (Danio rerio): A Prospective Controlled Intervention Study.

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.

Histopathological and Behavioral Impairments in Zebrafish (Danio rerio) Chronically Exposed to a Cocktail of Fipronil and Pyriproxyfen.

BACKGROUND: Lately, the high incidence of pesticide usage has attracted everyone's interest due to the serious effects produced. Fipronil (FIP) is a phenylpyrazole compound that acts on the insect's GABA neurotransmitter by inhibiting its activity. Moreover, the literature reports highlight its implication in neurodevelopmental abnormalities and oxidative stress production in different organisms. Similarly, pyriproxyfen (PYR) is known to affect insect activity by mimicking the natural hormones involved in the maturation of the young insects. The aim of the present study was to investigate the impact of the mixture of these pesticides on the tissues and behavior of zebrafish. METHODS: To assess the influence of this cocktail on zebrafish, three groups of animals were randomly selected and exposed to 0, 0.05, and 0.1 mg L-1 FIP and PYR mixture for five days. The fish were evaluated daily by the T-maze tests for locomotor activity and the light-dark test and recordings lasted four min. The data were quantified using the EthoVision software. RESULTS: Our results indicated significant changes in locomotor activity parameters that showed increased levels following exposure to the mixture of FIP and PYR. On the other hand, the mixture also triggered anxiety in the zebrafish, which spent more time in the light area than in the dark area. In addition, mixture-induced histological changes were observed in the form of numerous hemosiderin deposits found in various zebrafish tissues. CONCLUSIONS: The current findings indicate that the mixture of FIP and PYR can have considerable consequences on adult zebrafish and may promote or cause functional neurological changes in addition to histological ones.

Preliminary Results Regarding Sleep in a Zebrafish Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is one of the most salient developmental neurological diseases and remarkable similarities have been found between humans and model animals of ASD. A common method of inducing ASD in zebrafish is by administrating valproic acid (VPA), which is an antiepileptic drug that is strongly linked with developmental defects in children. In the present study we replicated and extended the findings of VPA on social behavior in zebrafish by adding several sleep observations. Juvenile zebrafish manifested hyperactivity and an increase in ASD-like social behaviors but, interestingly, only exhibited minimal alterations in sleep. Our study confirmed that VPA can generate specific ASD symptoms, indicating that the zebrafish is an alternative model in this field of research.

The Possible Role of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson's Disease.

BACKGROUND: As every organ within the body, the brain is also extremely susceptible to a plethora of noxious agents that change its chemistry. One component frequently found in current products against harmful species to crops is rotenone whose effect under prolonged exposure has been demonstrated to cause neurodegenerative disorders such as Parkinson's disease. The latest reports have indeed revealed that rotenone promotes Parkinson's in humans, but studies aiming to show congruent effects in zebrafish (Danio rerio) are lacking. Material and Methods. In this context, the aim of the present study was to demonstrate how chronic administration of rotenone for 3 weeks impairs the locomotor activity and sociability and induces oxidative stress in zebrafish. RESULTS: There were no statistically significant differences following the analysis of their social interaction and locomotor tests (p > 0.05). However, several exceptions have been noted in the control, rotenone, and probiotics groups when we compared their locomotor activity during the pretreatment and treatment interval (p < 0.05). We further assessed the role of rotenone in disturbing the detoxifying system as represented by three enzymes known as superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Despite the fact that there were no statistically significant changes within SOD and GPx levels between the control group and rotenone, probiotics, and rotenone + probiotics (p > 0.05), relevant changes have been observed between the analyzed groups (p < 0.05 and p < 0.005, respectively). On the other hand, significant differences (p < 0.05) have been observed for MDA when we analyzed the data between the control group and the other three groups. CONCLUSIONS: Our results suggest that rotenone can be successfully used to trigger Parkinson's disease-related symptomatology in zebrafish.

Parkinson's Disease-Induced Zebrafish Models: Focussing on Oxidative Stress Implications and Sleep Processes.

The complex yet not fully understood pathophysiology of Parkinson's disease includes an important molecular component consisting of oxidative status changes, thus leading to oxidative stress occurrence. While no particular evidence has been reported that describes the relationship between oxidative stress and the molecular mechanisms behind Parkinson's disease development, animal model studies has shown that oxidative stress induction could modulate Parkinson's disease symptomatology. Despite the inability to perfectly replicate human disease in animals and despite that Parkinson's disease has not been reported in any animal species, animal modeling is one of the most important tools in understanding the complex mechanisms of human disorders. In this way, this study is aimed at detailing this particular relationship and describing the molecular mechanisms underlying Parkinson's disease in animal models, focusing on the potential advantages and disadvantages of zebrafish in this context. The information relevant to this topic was gathered using major scientific database research (PubMed, Google Scholar, Web of Science, and Scopus) based on related keywords and inclusion criteria. Thus, it was observed that oxidative stress possesses an important role in Parkinson's disease as shown by numerous animal model studies, many of which are based on rodent experimental models. However, an emerging impact of the zebrafish model was observed in the research of Parkinson's disease pathological mechanisms with regard to disease development factors and the cause-effect relationship between oxidative stress and comorbidities (such as depression, hyposmia, fatigue, sleep disturbances, and cognitive deficits) and also with regard to the pharmacological potential of antioxidant molecules in Parkinson's disease treatment.

Vitamin C Attenuates Oxidative Stress and Behavioral Abnormalities Triggered by Fipronil and Pyriproxyfen Insecticide Chronic Exposure on Zebrafish Juvenile.

Chronic exposure to synthetic insecticides in the early life of a child can lead to a series of disorders. Several causes as parental age, maternal smoking, birth complications, and exposure to toxins such as insecticides on childhood can lead to Autism spectrum disorder (ASD) occurrence. The aim of this study was to evaluate the potential protective role of vitamin C (Vit. C) from children's supplements after 14 days chronic exposure to insecticide mixture fipronil (Fip) + pyriproxyfen (Pyr) on juvenile zebrafish for swimming performances, social behavior and oxidative stress associated with ASD model. Juvenile (14-17 mm) wild-type AB zebrafish (Danio rerio) (45 days) were exposed to relevant concentrations: vit. C (25 µg L-1), Fip (600 µg L-1/1.372 µM) + Pyr (600 µg L-1/1.89 µM), and [Fip (600 µg L-1/1.372 µM) + Pyr (600 µg L-1 /1.89 µM)] + vit. C (25 µg L-1). Our results showed that insecticides can disturb the social behavior of zebrafish during 14 days of the administration, decreased the swimming performances, and elevated the oxidative stress biomarkers of SOD (superoxide dismutase), GPx (glutathione peroxidase), and MDA (malondialdehyde). The vitamin C supplement significantly attenuated the neurotoxicity of insecticide mixture and oxidative stress. This study provides possible in vivo evidence to show that vitamin C supplements could attenuate oxidative stress and brain damage of fipronil and pyriproxyfen insecticide chronic exposure on zebrafish juvenile.

Acute exposure to gold induces fast changes in social behavior and oxidative stress of zebrafish (Danio rerio).

Gold is a noble metal having a long history of human usage and a variety of applications. The present paper was designed in order to see the changes on social and swimming behavior of zebrafish caused by acute gold exposure to high concentrations dissolved in aquatic medium from a standard solution with the highest purity. Some main oxidative stress markers were determined such as: superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and glutathione peroxidase (GPx). We also focused our attention on the bioaccumulation capacity of gold in exposed zebrafish and its competition with essential elements for the body: sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), iron (Fe), zinc (Zn) and copper (Cu). They were studied the effects of the follow gold concentrations dissolved in experimental aquariums: 1 mg L-1 (Au 1 mg/L), 2 mg L-1 (Au 2 mg/L), 4 mg L-1 (Au 4 mg/L) and 8 mg L-1 (Au 8 mg/L). Our data showed that each group treated with gold had a higher concentration compared with the others suggesting that it can be absorbed into the zebrafish body from environment and may be accumulated. The results obtained in the oxidative stress parameters demonstrated that it can produce changes as a response to its toxicological effects.

Acute exposure to methylmercury chloride induces fast changes in swimming performance, cognitive processes and oxidative stress of zebrafish (Danio rerio) as reference model for fish community.

Fishes are the first group of vertebrates that respond when the environment is contaminated with pollutants resulted from anthropogenic activities. The development of the toxicity tests is bringing new evidence about the toxicological effects of the pollutants upon the life forms. Behavioural abnormalities in the swimming performance and cognitive processes were well associated with the response of organisms to pollutants from environment. The aim of the paper was to study the behavioural changes of zebrafish (memory, swimming performances and aggression) and oxidative stress (superoxide dismutase and malondialdehyde) during 32 h of acute exposure with methylmercury (II) chloride to measure its neurotoxicity effects upon fish community. The experiments from this study tested and measured the fish community response to methylmercury concentrations (1 µg L-1 and 15 µg L-1) in the first hours after it contamination based on zebrafish model. The changes of the behaviour in the case of a fish species may lead in the end to their population reduction based on less reproductive success, lower food resource exploitation and problems in the predator avoidance. The behavioural tests described in the present study can be applied to measure the neurotoxicity of other metals compounds, to do plans and protocols for avoiding future ecological disasters. The behavioural changes of zebrafish exposed to methylmercury (II) chloride were similar to mammal models and they will have applications in future research.