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1-(Phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) is a selenoindolizine with an antidepressant-like effect in mice by regulation of the serotonergic system. This study investigated the involvement of dopaminergic and noradrenergic systems in the antidepressant-like action of MeSeI. For this purpose, Swiss male mice were pretreated with different antagonists, after 15 min, the MeSeI was administrated by intragastric (i.g.) via; after 30 min, the mouse behavior was assessed in the forced swimming test (FST). The action of MeSeI on the activity of monoamine oxidase (MAO) was determined. The pretreatment of mice with haloperidol (0.05 mg/kg, intraperitoneally, i.p.; non-selective dopamine receptor antagonist), sulpiride (50 mg/kg, i.p.; D2 receptor antagonist), yohimbine (1 mg/kg, i.p.; α2 receptor antagonist), and propranolol (2 mg/kg, i.p.; non-selective ß receptor antagonist), inhibited the anti-immobility action of MeSeI (50 mg/kg, i.g.) in the FST. This blocking effect was not observed when SCH23390 (0.01 mg/kg, i.p.; D1 receptor antagonist), and prazosin (1 mg/kg, i.p.; α1 receptor antagonist) were administered. The coadministration of subeffective doses of bupropion (3 mg/kg. i.g.; dopamine and noradrenaline reuptake inhibitor) and MeSeI (0.5 mg/kg. i.g.) reduced the immobility time in the FST. Furthermore, MeSeI inhibited MAO-A and B activities in vitro and ex vivo tests. These results suggest that MeSeI exerts its antidepressant-like effect via regulation of the D2, α2, and ß1 receptors and the inhibition of MAO-A and B activities. Molecular docking investigations corroborated these results. This study provides comprehensive insights into the antidepressant-like mechanism of MeSeI in mice, suggesting its potential as a novel antidepressant candidate.

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Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive molecules produced naturally by the body and by external factors. When these species are generated in excessive amounts, they can lead to oxidative stress, which in turn can cause cellular and tissue damage. This damage is known to contribute to the aging process and is associated with age-related conditions, including cardiovascular and neurodegenerative diseases. In recent years, there has been an increased interest in the development of compounds with antioxidant potential to assist in the treatment of disorders related to oxidative stress. In this way, compounds containing sulfur (S) and/or selenium (Se) have been considered promising due to the relevant role of these elements in the biosynthesis of antioxidant enzymes and essential proteins with physiological functions. In this context, studies involving heterocyclic nuclei have significantly increased, notably highlighting the indolizine nucleus, given that compounds containing this nucleus have been demonstrating considerable pharmacological properties. Thus, the objective of this research was to evaluate the in vitro antioxidant activity of eight S- and Se-derivatives containing indolizine nucleus and different substituents. The in vitro assays 1,1-diphenyl-2-picryl-hydrazil (DPPH) scavenger activity, ferric ion (Fe3+) reducing antioxidant power (FRAP), thiobarbituric acid reactive species (TBARS), and protein carbonylation (PC) were used to access the antioxidant profile of the compounds. Our findings demonstrated that all the compounds showed FRAP activity and reduced the levels of TBARS and PC in mouse brains homogenates. Some compounds were also capable of acting as DPPH scavengers. In conclusion, the present study demonstrated that eight novel organochalcogen compounds exhibit antioxidant activity.

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Redox imbalance leads to oxidative stress that causes irreversible cellular damage. The incorporation of the antioxidant element selenium (Se) in the structure of pyridinium salts has been used as a strategy in chemical synthesis and can be useful in drug development. We investigated the antioxidant activity of Se-containing pyridinium salts (named Compounds 3A, 3B, and 3C) through in vitro tests. We focused our study on liver protein carbonylation, liver lipoperoxidation, free radical scavenging activity (1,1-diphenyl-2-picryl-hydrazil [DPPH]; 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid [ABTS]), and enzyme-mimetic activity assays (glutathione S-transferase [GST]-like; superoxide dismutase [SOD]-like). In addition, 2-(4-chlorophenyl)-2-oxoethyl)-2-((phenylselanyl)methyl)pyridin-1-ium bromide (3C) was selected to evaluate the acute oral toxicity in mice due to the best antioxidant profile. The three compounds were effective in reducing the levels of protein carbonylation and lipoperoxidation in the liver in a µM concentration range. All compounds demonstrated scavenger activity of DPPH and ABTS radicals, and GST-like action. No significant effects were detected in the SOD-like assay. Experimental data also showed that the acute oral treatment of mice with Compound 3C (50 and 300 mg/kg) did not cause mortality or change markers of liver and kidney functions. In summary, our findings reveal the antioxidant potential of Se-containing pyridinium salts in liver tissue, which could be related to their radical scavenging ability and mimetic action on the GST enzyme. They also demonstrate a low toxicity potential for Compound 3C. Together, the promising results open space for future studies on the therapeutic application of these molecules.

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Monensin poisoning is uncommon and has been rarely reported in birds. This work aimed to described clinical-pathological aspects of an outbreak of monensin poisoning in captive and free-ranging birds. Thirty-seven of 600 captive birds fed a diet containing 893.19 mg/kg of monensin died within 10 days (mortality 6.17%). There was no ionophore antibiotics on the feed label supplied to captive birds, which established an error in feed production. Necropsies were performed on twelve animals: Muscovy duck (Cairina moschata) (2/12), greater rhea (Rhea americana) (2/12), black-necked swan (Cygnus melancoryphus) (2/12), garganey (Anas querquedula) (1/12), ostrich (Struthio camelus) (1/12), and common pigeon (Columbus livia) (4/12). These four common pigeons were free-ranging birds and died after eating the same contaminated feed. Birds were mainly found dead, however in animals which clinical signs were observed (Columba livia, Rhea americana, Cairina moschata, Anas querquedula, and Struthio camelus), they included incoordination, inability to stand, and intense prostration, that ranged from 24 to 72 h until death. Grossly, five birds had focally extensive pale firm areas in the myocardium and two had in the skeletal muscles, one being concomitant lesions. Histologically, muscle necrosis and degeneration were observed in striated musculature (skeletal and/or heart) in all birds analyzed. Monensin poisoning outbreaks can affect free-ranging birds that are fed on external feeders, as well as captive birds, due to an error in the feed formulation.

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Neoplasms in wild felids are more frequently observed in captive animals, of which clinicopathological features of pulmonary tumors are not commonly described. This study aimed to describe the clinical and pathological aspects of a case of diffuse pulmonary acinar adenocarcinoma in a 23-year-old, captive lioness with clinical history of dyspnea, progressive weight loss and inappetence. At necropsy, the lungs were mildly pale, moderately firm, and the pleural surface was diffusely irregular with multifocal to coalescent, grey to white areas. No masses or superficial nodules were detected, but, on the cut surface, there were numerous, spherical, firm, white to yellow areas up to 0.5 cm in diameter affecting all pulmonary lobes. Histologically, in the lungs, there were extensive, non-delineated areas of neoplastic proliferation of columnar, ciliated epithelial cells arranged in irregular tubuloacinar structures. Immunohistochemical analysis revealed immunolabeling of neoplastic cells for pan-cytokeratin and thyroid transcription factor-1. Napsin-A exhibited only scarce and scattered immunolabeling in the neoplastic cells. The gross, histologic and immunohistochemical findings confirmed the final diagnosis of primary diffuse pulmonary adenocarcinoma.

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Selenium is an essential trace element in living organisms, and is present in selenoenzymes with antioxidant activity, like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). The search for small selenium-containing molecules that mimic selenoenzymes is a strong field of research in organic and medicinal chemistry. In this review, we review the synthesis and bioassays of new and known organoselenium compounds with antioxidant activity, covering the last five years. A detailed description of the synthetic procedures and the performed in vitro and in vivo bioassays is presented, highlighting the most active compounds in each series.

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RATIONALE: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results. OBJECTIVES AND METHODS: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5-50 mg/kg, intragastric-i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg). RESULTS: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally-i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous-s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice. CONCLUSION: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression.

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OBJECTIVES: The relationship between psychosocial factors/mental health/depressive symptoms and inadequate gestational weight (GW) change remains poorly understood. Thus, the aim of this study was to evaluate the association between depressive symptoms and inadequate GW change according to the criteria established by the Institute of Medicine in 2009. METHODS: This cross-sectional study was part of a prospective cohort, and conducted in Botucatu, São Paulo, Brazil. Pregnant women who received prenatal care at basic health care units in the city participated in the study (n = 297). The Edinburgh Postnatal Depression Scale was used to assess depressive symptoms during pregnancy, and the cutoff point used for the positive screening of depressive symptoms was ≥13. The association between depressive symptoms and two outcomes (insufficient and excessive weight change during second and third trimesters) was investigated using logistic regression models with adjustment for potential confounders. Crude and adjusted effect measures (odds ratios) and their relevant 95% confidence intervals were estimated. RESULTS: There was an association between a positive score for depression during pregnancy and insufficient GW gain. No association was observed between depressive symptoms and excessive GW gain. CONCLUSIONS: The presence of depressive symptoms significantly increased the chance of insufficient GW change. This finding enhances the need for screening for depression in prenatal care.

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Abstract Objectives: to identify variables associated with the presence of a companion in the delivery room and its association with breastfeeding (BF) in the first hour of life. Methods: cross-sectional analysis of data from a cohort study (n=344). To investigate the factors associated with the presence of a companion during childbirth and breastfeeding in the first hour; we performed Poisson regression analyses, considering p<0.05 as the level of statistical significance. Results: 93.9% of the pregnant women had a companion in the delivery room, and no association was found between socioeconomic, obstetric and neonatal characteristics of the mother-child binomial and the presence of a companion. In a univariate analysis, the absence of a companion reduced the frequency of breastfeeding in the first hour (PR=0.64; CI95%=0.42-0.96), a result that was not confirmed in the adjusted analyses (PR=0.79; CI95%=0.54-1.15). Secondly, it was identified that the five minutes Apgar score was associated with first hour breastfeeding (PR=1.27; CI95%=1.14-1.40) regardless of the other factors. Conclusions: most women in the cohort had a companion in the delivery room, with no differences according to socioeconomic, obstetric and neonatal variables. The frequency of first hour breastfeeding was high; however, it was lower in the absence of a companion but this association was not independent of other factors.

Resumo Objetivos: identificar variáveis associadas à presença de acompanhante na sala de parto e sua associação com o aleitamento materno (AM) na primeira hora de vida. Métodos: análise transversal de dados provenientes de um estudo de coorte (n=344). Para investigação dos fatores associados entre a presença de companhia durante o parto e o AM na primeira hora foram realizadas análises de regressão de Poisson, considerando p<0,05 como nível de significância estatística. Resultados: 93,9% das parturientes tiveram acompanhante na sala de parto, não sendo encontrada associação entre características socioeconômicas, obstétricas e neonatais do binômio mãe-filho e esta presença. Em análise univariada, a ausência de acompanhante reduziu a frequência de AM na primeira hora (RP=0,64; IC95%=0,42-0,96), resultado que não se confirmou nas análises ajustadas (RP=0,79; IC95%=0,54-1,15). Secundariamente, identificou-se que o Apgar no quinto minuto associou-se com AM na primeira hora (RP=1,27; IC95%=1,14-1,40) independentemente dos demais fatores. Conclusões: a maioria das mulheres da coorte contou com acompanhante na sala de parto, sem diferenças segundo variáveis socioeconômicas, obstétricas e neonatais. A frequência de AM na primeira hora também foi alta e menor na ausência de acompanhante, contudo, essa associação não se mostrou independente de outros fatores.

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Previous studies that assessed risk factors for venous thromboembolism (VTE) in COVID-19 patients have shown inconsistent results. Our aim was to investigate VTE predictors by both logistic regression (LR) and machine learning (ML) approaches, due to their potential complementarity. This cohort study of a large Brazilian COVID-19 Registry included 4120 COVID-19 adult patients from 16 hospitals. Symptomatic VTE was confirmed by objective imaging. LR analysis, tree-based boosting, and bagging were used to investigate the association of variables upon hospital presentation with VTE. Among 4,120 patients (55.5% men, 39.3% critical patients), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95% CI 1.11-2.02); being an ex-smoker (OR 1.44, 95% CI 1.03-2.01); surgery ≤ 90 days (OR 2.20, 95% CI 1.14-4.23); axillary temperature (OR 1.41, 95% CI 1.22-1.63); D-dimer ≥ 4 times above the upper limit of reference value (OR 2.16, 95% CI 1.26-3.67), lactate (OR 1.10, 95% CI 1.02-1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01-1.18); and neutrophil count (OR 1.04, 95% CI 1.005-1.075) were independent predictors of VTE. Atrial fibrillation, peripheral oxygen saturation/inspired oxygen fraction (SF) ratio and prophylactic use of anticoagulants were protective. Temperature at admission, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. By using ML and LR analyses, we showed that D-dimer, axillary temperature, neutrophil count, CRP and lactate levels are risk factors for VTE in COVID-19 patients.

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