Dopaminergic Modulation and Computational ADMET Insights for the Antidepressant-like Effect of N-(3-(Phenylselanyl)prop-2-yn-1-yl)benzamide.

The compound N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), which combines a selenium atom and a benzamide nucleus in an organic structure, has demonstrated a fast antidepressant-like effect in mice. This action is influenced by the serotonergic system and represents a promising development in the search for novel antidepressant drugs to treat major depressive disorder (MDD), which often resists conventional treatments. This study aimed to further explore the mechanism underlying the antidepressant-like effect of SePB by investigating the involvement of the dopaminergic and noradrenergic systems in the tail suspension test (TST) in mice and evaluating its pharmacokinetic profile in silico. Preadministration of the dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally (i.p.)), a nonselective antagonist of dopamine (DA) receptors, SCH23390 (0.01 mg/kg, subcutaneously (s.c.)), a D1 receptor antagonist, and sulpiride (50 mg/kg, i.p.), a D2/3 receptor antagonist, before SePB (10 mg/kg, intragastrically (i.g.)) prevented the anti-immobility effect of SePB in the TST, demonstrating that these receptors are involved in the antidepressant-like effect of SePB. Administration of the noradrenergic antagonists prazosin (1 mg/kg, i.p.), an α1-adrenergic antagonist, yohimbine (1 mg/kg, i.p.), an α2-adrenergic antagonist, and propranolol (2 mg/kg, i.p.), a ß-adrenergic antagonist, did not block the antidepressant-like effect of SePB on TST, indicating that noradrenergic receptors are not involved in this effect. Additionally, the coadministration of SePB and bupropion (a noradrenaline/dopamine reuptake inhibitor) at subeffective doses (0.1 and 3 mg/kg, respectively) produced antidepressant-like effects. SePB also demonstrated good oral bioavailability and low toxicity in computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses. These findings suggest that SePB has potential as a new antidepressant drug candidate with a particular focus on the dopaminergic system.

N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system.

RATIONALE: Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects. OBJECTIVE: To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF3SePB) in mice and the involvement of the serotonergic and noradrenergic systems. METHODS: Male Swiss mice were treated with CF3SePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF3SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3SePB (50 mg/kg, i.g.), and after 30 min of CF3SePB administration the FST was performed. RESULTS: CF3SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT1A and 5-HT3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF3SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice. CONCLUSION: This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.

1-(Phenylselanyl)-2-(p-tolyl)indolizine: A selenoindolizine with potential antidepressant-like activity in mice mediated by the modulation of dopaminergic and noradrenergic systems.

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.

Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia-a prospective, single-center, analytical, cross-sectional study.

Background: Patients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. Objectives: To evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. Methods: We performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. Results: Higher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. Conclusion: Patients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays.

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.

Liposome-siderophore conjugates loaded with moxifloxacin serve as a model for drug delivery against Mycobacterium tuberculosis.

Tuberculosis (TB) is an infectious disease that annually affects millions of people, and resistance to available antibiotics has exacerbated this situation. Another notable characteristic of Mycobacterium tuberculosis, the primary causative agent of TB, is its ability to survive inside macrophages, a key component of the immune system. In our quest for an effective and safe treatment that facilitates the targeted delivery of antibiotics to the site of infection, we have proposed a nanotechnology approach based on an iron chelator. Iron chelators are the primary mechanism by which bacteria acquire iron, a metal essential for their metabolism. Four liposomes were synthesized and characterized using the dynamic light scattering technique (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). All of these methods revealed the presence of spherical particles, approximately 200 nm in size. NTA indicated a concentration of around 1011 particles/mL. We also developed and validated a high-performance liquid chromatography method for quantifying Moxifloxacin to determine encapsulation efficiency (EE) and release profiles (RF). The EE was 51.31 % for LipMox and 45.76 % for LipIchMox. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the phagocytosis of liposomal vesicles by macrophages. Functionalizing liposomes with iron chelators can offer significant benefits for TB treatment, such as targeted drug delivery to intracellular bacilli through the phagocytosis of liposomal particles by cells like macrophages.

Disruption Of Non-COVID-19 Health Care In Latin America During The Pandemic: Effects On Health, Lessons For Policy.

COVID-19 had severe direct and indirect effects on health and well-being in Latin America. To understand the extent to which disruptions among non-COVID-19-related health services affected population health, we used administrative data from the period 2015-21 to examine public hospital discharges and mortality for conditions amenable to health care in four Latin American countries: Brazil, Ecuador, Mexico, and Peru. Between March 2020 and December 2021, hospitalization rates for these conditions declined by 28 percent and mortality rates increased by 15 percent relative to prepandemic years. Noncommunicable diseases accounted for 89 percent of this rise in mortality. The poorest states in each country experienced relatively larger increases in mortality. Our results, which focus on the health effects of service disruption, suggest that maintaining health care services in this region during the pandemic could have avoided at least 96,000 deaths. Policies should focus on maintaining essential health care services during emergencies, particularly for patients with noncommunicable diseases, and on minimizing negative consequences by ensuring coordinated and continuous care; leveraging alternative modalities of care, such as telemedicine; broadening the role of nonphysician health care workers; and expanding options for medication delivery.

Recent Advances in the Synthesis and Antioxidant Activity of Low Molecular Mass Organoselenium Molecules.

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.

Clinical, epidemiological, and laboratory profiles of bacterial infection or colonization among patients hospitalized in COVID-19 and non-COVID-19 intensive care units (ICUs) in Southeast Pará / Perfis clínico, epidemiológico e laboratorial de infecção ou colonização bacteriana em pacientes internados em unidades de terapia intensiva (UTIs) COVID-19 e não COVID-19 no sudeste do Pará

Objectives: To compare the clinical, epidemiological, and laboratory profiles of bacterial infection or colonization among patients hospitalized in COVID-19 and non-COVID-19 intensive care units (ICUs) in Southeast Pará, Brazil. Methods:This was a retrospective analytical study based on the analyses of electronic medical records and microbiological reports of patients admitted to the ICU of a regional hospital located in Pará in the Brazilian Amazon due to complications associated with COVID-19 and other causes from March 2020 to December 2021. The sample consisted of data from the medical records of 343 patients collected after approval by the ethics and research committee (opinion number 5281433) was granted. The data extracted from the bacteriological and antibiogram culture reports were analyzed to characterize the clinical-epidemiological profile of the patients. The data were transferred and tabulated in Microsoft Excel 2019 to conduct a descriptive analysis, and the associated statistical analyses were performed using Stata 17.0 statistical soft-ware. Results: Of the total patients, 59.5% were hospitalized in the COVID-19 ICU and 40.5% were hospitalized in the non-COVID-19 ICU. Most individuals admitted to the COVID-19 ICU and non-COVID-19 ICU were aged between 66 and 78 years and between 54 and 66 years, respectively. The hospitalization duration in the COVID-19 ICU was fewer than 15 days, whereas that in the non-COVID-19 ICU was 15 to 30 days. Deaths were more frequent in the Covid-19 ICU compared to the non-Covid-19 ICU (64% versus 41%). In contrast, hospital discharge was more frequent in the non-Covid-19 ICU (58.3% versus 34.8%).The most prevalent comorbidity in both ICUs was circulatory system disease. Gram-negative bacteria were the most frequent etiological agent in both groups and were present in 63.1% of the cultures analyzed. Regarding the phenotypic profile of resistance, carbapenemase production was detected in 43.0% of the cultures analyzed. Multidrug resistance against antimicrobial drugs was more frequent in the non-COVID-19 ICU (55.7%). Most of the antimicrobial drug prescriptions for were empirical. Conclusions: The recurrence of secondary infections and bacterial colonization in both COVID-19 and non-COVID-19 ICU patients should not be underestimated. The clinical, microbiological, and bacterial resistance profiles elucidated in this study highlight the need to develop and implement holistic and assertive strategies to control and mitigate these problems. Which will contribute to an improved prognosis for patients and quality of life patients (AU).

Objetivos: Comparar o perfil clínico, epidemiológico e laboratorial das infecções ou colonizações bacterianas entre pacientes internados em UTI COVID-19 e não-COVID-19 no Sudeste do Pará, Brasil. Métodos: Trata-se de um estudo analítico retrospectivo baseado na análise de prontuários eletrônicos e laudos microbiológicos de pacientes internados em um hospital regional localizado no Pará, na Amazônia brasileira, devido a complicações associadas à COVID-19 e outras causas no período de março de 2020 a dezembro de 2021. A amostra foi constituída por dados dos prontuários de 343 pacientes coletados após aprovação pelo Comitê de ética em Pesquisa (parecer número 5281433). Os dados extraídos dos laudos de cultura bacteriológica e antibiograma foram analisados para caracterizar o perfil clínico-epidemiológico dos pacientes. Foram realizadas análises descritivas e inferenciais utilizando o Stata 17.0 statistical software. Resultados: Do total de pacientes, 59,5% estavam internados na UTI COVID-19 e 40,5% na UTI não-COVID-19. A maioria dos indivíduos apresentavam idades entre 54 e 78. O tempo de internação na UTI COVID-19 foi inferior a 15 dias, enquanto na UTI não-CO-VID-19 foi de 15 a 30 dias. Os óbitos foram mais frequentes na UTI Covid-19 em relação à UTI não-Covid-19 (64% versus 41%). Em contrapartida, a alta hospitalar foi mais frequente na UTI não Covid-19 (58,3% versus 34,8%). A comorbidade mais prevalente em ambas as UTIs foi a doença do aparelho circulatório. As bactérias Gram-negativas foram os agentes etiológicos mais frequentes em ambos os grupos e estiveram presentes em 63,1% das culturas analisadas. Em relação ao perfil fenotípico de resistência, a produção de carbapenemase foi detectada em 43,0% das culturas analisadas. A multirresistência aos antimicrobianos foi mais frequente na UTI não COVID-19 (55,7%). A maioria das prescrições de antimicrobianos foram empíricas. Conclusões: A recorrência de infecções secundárias e colonizações bacterianas em pacientes com COVID-19 e não COVID-19 em UTIs não devem ser subestimadas. Os perfis de resistência bacteriana elucidados neste estudo destacam a necessidade da implementação de estratégias holísticas e assertivas visando o controle e mitigação dessa problemática, o que contribuirá para a melhoria do prognóstico, bem como, a qualidade e segurança dos paciente (AU).

The Influence of Body Fat and Lean Mass on HbA1c and Lipid Profile in Children and Adolescents with Type 1 Diabetes Mellitus.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications and HbA1c. This cross-sectional observational study of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values, analyzing biochemical and body composition measurements. A Shapiro-Wilk test with Lilliefors correction, a non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-I ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

Antidepressant-like Effect of 1-(2-(4-(4-Ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one in Mice: Evidence of the Contribution of the Serotonergic System.

Major depressive disorder (MDD) is a psychiatric disorder that affects a large portion of the population, with dysregulation of the serotonergic system, which is deeply involved in both the pathophysiology of MDD and mechanism of action of many antidepressants. Current pharmacological therapies do not meet the neurobiological needs of all depressed individuals, making the development of new antidepressants necessary. In recent decades, compounds containing triazoles have become promising due to their range of biological activities, including antidepressant activity. In this study, we evaluated the antidepressant-like effect of a hybrid containing triazole and acetophenone, 1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one (ETAP) (0.5-5 mg/kg), in the forced swimming test (FST) and tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in this effect. Our findings demonstrated that ETAP exhibited an antidepressant-like effect from the dose of 1 mg/kg and that this effect is modulated by 5-HT2A/2C and 5-HT4 receptors. We also demonstrated that this effect may be related to inhibition of monoamine oxidase A activity in the hippocampus. Additionally, we evaluated the in silico pharmacokinetic profile of ETAP, which predicted its penetration into the central nervous system. ETAP exhibited a low potential for toxicity at a high dose, making this molecule interesting for the development of a new therapeutic strategy for MDD.

Avaliação dos registros de enfermagem sobre oxigenação por membrana extracorpórea em equipe multidisciplinar treinada / Evaluation of nursing records on extracorporal membrane oxygenation after multidisciplinary training / Evaluación de registros de enfermería sobre oxigenación por membrana extracorpórea después de entrenamiento multidisciplinar

Objetivos: comparar o conteúdo dos registros de enfermagem referente à oxigenação por membrana extracorpórea (ECMO) entre os períodos de pré e pós-treinamento da equipe multidisciplinar. Método: estudo retrospectivo realizado em uma unidade de terapia intensiva adulto, com pacientes em uso de ECMO entre 2012 e 2019. Foram analisadas as informações das anotações, evoluções e prescrições de enfermagem sobre a ECMO. Resultados: foram incluídos 194 registros de enfermagem, que evidenciaram melhora na qualidade da evolução de enfermagem referente às informações da ECMO no período pós-treinamento. Dentre as informações, destaca-se a qualidade do registro sobre o circuito e a membrana. Conclusão: o treinamento multidisciplinar em ECMO foi fundamental para a melhoria das informações nas evoluções de enfermagem. Contudo, a continuidade de treinamentos se faz essencial para manutenção adequada dos registros de enfermagem que envolvem este suporte

Objectives: to compare nursing records regarding extracorporeal membrane oxygenation (ECMO) between pre- and post-multidisciplinary training. Method:A retrospective study was conducted in an Intensive Care Unit (ICU) with patients using ECMO, between 2012 and 2019. Notes, evolutions and nursing prescriptions on ECMO were analyzed. Results: the 194 nursing records analyzed revealed an improvement in the quality of nursing records regarding ECMO information post-training. Among the information, the quality of circuit and membrane records stands out. Conclusion: multidisciplinary training in ECMO was fundamental for improving information in nursing evolutions. However, continued training is essential for the proper maintenance of nursing records regarding this suppor

Objetivos: comparar el contenido de los registros de enfermería con respecto a la oxigenación por membrana extracorpórea (ECMO) entre los períodos pre y pos-entrenamiento del equipo multidisciplinario. Método: estudio retrospectivo, realizado en una unidad de cuidados intensivos (UCI), con pacientes en uso de ECMO entre 2012 y 2019. Se analizó información de notas, evoluciones y prescripciones de enfermería sobre ECMO. Resultados: se incluyeron 194 registros de enfermería, en los cuales se observó una mejora de la calidad en las evoluciones de enfermería respecto a la información de la ECMO en el período posterior al entrenamiento. Entre las informaciones destaca la calidad del registro en circuito y la membrana tras el entrenamiento. Conclusión: el entrenamiento multidisciplinar en ECMO fue fundamental para mejorar la información en los registros de enfermería. Sin embargo, la continuidad del entrenamiento es clave para el correcto mantenimiento de los registros de enfermería en relación con este apoyo

Intranasal in situ gelling liquid crystal for delivery of resveratrol ameliorates memory and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is an illness that affects people aged 65 or older and affects around 6.5 million in the United States. Resveratrol is a chemical obtained from natural products and it exhibits biological activity based on inhibiting the formation, depolymerization of the amyloid, and decreasing neuroinflammation. Due to the insolubility of this compound; its incorporation in surfactant-based systems was proposed to design an intranasal formulation. A range of systems has been produced by mixing oleic acid, CETETH-20 and water. Polarised light microscopy (PLM), small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) confirm the initial liquid formulation (F) presented as microemulsion (ME). After dilution, the gelled systems were characterized as hexagonal mesophase and they showed feasibility proprieties. Pharmacological assays performed after intranasal administration showed the ability to improve learning and memory in animals, as well as remission of neuroinflammation via inhibition of interleukin.

Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice.

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.

O vazio avassalador: a função desobjetalizante num quadro de melancolia / The overwhelming emptiness: the deobjectifying function in a melancholia setting

O artigo apresenta fragmentos clínicos do atendimento de uma paciente com marcados traços de melancolia, suas nuances de culpa inconsciente e suas impossibilidades de simbolização. Para refletir sobre o caso, o texto traz à tona as postulações de André Green acerca da função desobjetalizante e do narcisismo negativo. O objeto que não se deixa apagar ocupa o espaço psíquico que deveria ficar vazio para que o desejo e o ego do bebê possam se estruturar. Isto ocorre quando o trabalho do negativo fracassou em sua função de negativação do objeto primário. Considerando que o sujeito melancólico experimenta a perda do objeto como uma perda de si, refletimos também sobre a suportabilidade do estado de desamparo presente no masoquismo erógeno primário, o que nos leva às pontuações de Rosenberg acerca do masoquismo mortífero e do masoquismo guardião da vida(AU)

The paper presents some clinical fragments of a patient with marked traces of melancholia, nuances of unconscious guilt and impossibilities of symbolization. We bring up André Green’s postulations about the deobjectifying function and negative narcissism. The object that cannot be erased occupies the psychic space that should be left empty so that the baby’s desire and ego can be structured. This occurs when the work of the negative has failed in its function of negating the primary object. Considering that the melancholic subject experiences the loss of the object as a loss of himself, we will also think about the be arability of the state of helplessness present in primary erogenous masochism, which leads us to Rosenberg’s scores about deadly masochism and life-preserving masochism(AU)

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT2A/C Receptors.

The monoaminergic dysfunction plays a central role in major depressive disorder (MDD), a mental disturbance associated with constant feeling of sadness and lack of interest. The available treatments do not present a desirable efficacy and some of them provoke several adverse effects. In this context, organoselenium compounds and molecules containing the indolizine nucleus have demonstrated interesting pharmacological properties, including antidepressant-like effects. In this study, the antidepressant-like effect of 2-phenyl-1-(phenylselanyl)indolizine (SeI), a selenium-containing indolizine derivative, was investigated on the forced swimming test (FST) and on the tail suspension test (TST) in male Swiss mice. The involvement of the serotonergic system in this effect was also accessed. The selenium compound SeI (10-100 mg/kg, intragastrical (i.g.)) was administered 0.5 h before the behavioral tests, and it diminished the immobility on both FST and TST experiments, which is an indication of antidepressant-like effect. No changing in the locomotor motion was observed in the open-field test (OFT). The anti-immobility effect of SeI was not altered by the preadministration of the selective serotonergic receptor antagonists ondansetron (1 mg/kg, intraperitoneally (i.p.), antagonist of 5-HT3 receptor) and WAY100635 (0.1 mg/kg, subcutaneous route (s.c.), antagonist of 5-HT1A receptor). In contrast, the preadministration of ketanserin (1 mg/kg, i.p., antagonist of 5-HT2A/C receptor) blocked this effect, demonstrating that the antidepressant-like effect of SeI involves 5-HT2A/C. In addition, molecular docking studies showed a strong interaction between SeI and the receptors of 5-HT2A and 5-HT2C. The toxicological results demonstrated that SeI has low potential to cause adverse effects in mice. It was found that the antidepressant-like effect of SeI is related to modulation of the serotonergic system, and this selenium compound could be included in new treatment approaches for MDD.

Detection of SARS-CoV-2 virus via dynamic light scattering using antibody-gold nanoparticle bioconjugates against viral spike protein.

Mass testing for the diagnosis of COVID-19 has been hampered in many countries owing to the high cost of genetic material detection. This study reports on a low-cost immunoassay for detecting SARS-CoV-2 within 30 min using dynamic light scattering (DLS). The immunosensor comprises 50-nm gold nanoparticles (AuNPs) functionalized with antibodies against SARS-CoV-2 spike glycoprotein, whose bioconjugation was confirmed using transmission electron microscopy (TEM), UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and surface-enhanced Raman scattering spectroscopy (SERS). The specific binding of the bioconjugates to the spike protein led to an increase in bioconjugate size, with a limit of detection (LOD) 5.29 × 103 TCID50/mL (Tissue Culture Infectious Dose). The immunosensor was also proven to be selective upon interaction with influenza viruses once no increase in size was observed after DLS measurement. The strategy proposed here aimed to use antibodies conjugated to AuNPs as a generic platform that can be extended to other detection principles, enabling technologies for low-cost mass testing for COVID-19.

Persistent, new-onset symptoms and mental health complaints in Long COVID in a Brazilian cohort of non-hospitalized patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections lead to acute- and chronic Long COVID (LC) symptoms. However, few studies have addressed LC sequelae on brain functions. This study was aimed to examine if acute symptoms of coronavirus disease 2019 (COVID-19) would persist during LC, and if memory problems would be correlated with sleep, depressive mood, or anxious complaints. METHODS: Our work followed a cohort of 236 patients from two public hospitals of the Federal District in mid-western Brazil. Patients' interviews checked for clinical symptoms during acute and LC (5-8 months after real-time reverse transcription polymerase chain reaction, RT-qPCR). RESULTS: Most cases were non-hospitalized individuals (86.3%) with a median age of 41.2 years. While myalgia (50%), hyposmia (48.3%), and dysgeusia (45.8%) were prevalent symptoms in acute phase, fatigue (21.6%) followed by headache (19.1%) and myalgia (16.1%) commonly occurred during LC. In LC, 39.8% of individuals reported memory complaints, 36.9% felt anxious, 44.9% felt depressed, and 45.8% had sleep problems. Furthermore, memory complaints were associated with sleep problems (adjusted OR 3.206; 95% CI 1.723-6.030) and depressive feelings (adjusted OR 3.981; 95% CI 2.068-7.815). CONCLUSIONS: The SARS-CoV-2 infection leads to persistent symptoms during LC, in which memory problems may be associated with sleep and depressive complaints.

Alterações hepáticas e renais em trabalhadores rurais decorrentes da exposição a agrotóxicos: revisão sistemática / Liver and kidney changes resulting from exposure to pesticides in rural workers: systematic review

O objetivo deste estudo foi revisar a literatura científica acerca da exposição dos trabalhadores rurais aos agrotóxicos e a atuação desses agentes sobre as funções dos sistemas hepático e renal. O estudo em questão se trata de uma revisão sistemática produzida de acordo com a metodologia Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Para esta revisão foram feitas buscas nas bases Medline, PubMed, Scielo e Lilacs, nas quais foram inclusos artigos escritos em português e inglês no período de 2009 a 2018. Os descritores em saúde utilizados para a pesquisa foram: agroquímicos, trabalhadores rurais, saúde do trabalhador e biomarcadores. De 52 artigos selecionados, apenas oito preencheram os critérios de inclusão desta revisão. Após a análise dos oito artigos, pôde-se observar que os marcadores bioquímicos hepáticos citados com maior frequência nos artigos foram as transaminases, aspartato aminotransferase e alanina aminotransferase, presentes em todos os estudos (100%, n=8), seguido da gama-glutamiltransferase encontrada em 75% dos artigos (n=6). Por outro lado, os marcadores renais citados nos artigos foram apenas creatinina e ureia, com uma frequência de 62,5% (n=5) e 50% (n=4), respectivamente. Esses marcadores apresentaram-se dentro da normalidade em todos os estudos. Dessa forma, conclui-se que não houve evidências de alterações nos marcadores renais e hepáticos, porém os artigos relatam a existência de uma diferença entre o grupo exposto, trabalhadores que estavam em contato com agrotóxicos, e o grupo controle.

This study aimed to review the scientific literature about the exposure of rural workers to pesticides and their effects on the functions of the hepatic and renal systems. The study in question is a systematic review produced according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology. For that, we searched the databases of Medline, PubMed, Scielo, and Lilacs, and articles written in Portuguese and English from 2009 to 2018 were included. The health descriptors used for the research were: agrochemicals, rural workers, occupational health, and biomarkers. Only eight out of the 52 articles selected initially met the inclusion criteria for this review. Their analysis showed that the most frequently cited liver biochemical markers were transaminases, aspartate aminotransferase, and alanine aminotransferase, present in all studies (100.0%, n=8). These were followed by the range-glutamyltransferase, found in 75.0% of the articles (n=6). On the other hand, the renal markers used in the articles were only creatinine and urea, with a frequency of 62.5% (n=5) and 50.0% (n=4), respectively. These markers were normal in all studies. Thus, we concluded that there was no evidence of changes in renal and hepatic markers. However, the articles do report differences between the exposed group, workers who were in contact with pesticides, and the control group.

Isolamento de amebas de vida livre potencialmente patogênicas em piscinas de uso coletivo localizadas no município de Redenção, Pará, Brasil / Isolation of potentially pathogenic free-living amoebae in swimming pools for collective use located in the municipality of Redenção, Pará, Brazil

Objetivo Isolar amebas dos gêneros Acanthamoeba e Naegleria em piscinas de uso coletivo do município de Redenção, Pará, Brasil. Métodos A identificação dessas amebas se deu a partir de amostras retiradas de piscinas de uso coletivo de quatro clubes da cidade. As análises foram realizadas a partir do exame direto a fresco, cultura, análise morfológica após coloração de Gram e teste de exflagelação, seguindo o protocolo descrito por Carlesso, Artuso e Rott. Resultados As amebas de vida livre foram encontradas em 41,67% das amostras, com predomínio das do gênero Acanthamoeba (63,2%) no exame direto a fresco. No clube A, localizado no setor Serrinha, houve predominância dessas amebas em relação às demais (8,34%). As amostras obtidas por swabs apresentaram 73,69% de formas evolutivas em comparação à análise feita apenas na água das piscinas. A confirmação dos gêneros das amebas presentes nas amostras feita através da coloração de Gram encontrou um perfil de identificação diferente, sendo que nesse exame a ameba de gênero Naegleriaspp. se sobressaiu perante a de gênero Acanthamoeba (61,11% e 38,89%, respectivamente). Conclusão Os resultados do estudo confirmam a presença de isolados potencialmente patogênicos de amebas de vida livre em piscinas de uso coletivo, o que pode significar um risco à saúde pública.

Objective To isolate amoebae of the genera Acanthamoeba and Naegleria in swimming pools for collective use in the municipality of Redenção, Pará, Brazil. Methods The identification of these amoebae was determined from samples of swimming pools for collective use in four private clubs in the city. The analysis methodology was performed based on direct fresh examination, culture, morphological analysis after Gram staining and exflagellation test, following the protocol described by Carlesso, Artuso and Rott. Results The frequency of free-living amoebae was 41.67%, with a predominance of the Acanthamoeba genus (63.2%) in direct fresh examination. At club A, located in the Serrinha sector, the frequency of these amoebae was higher than the others (8.34%). The samples obtained by swabs showed 73.69% of evolutionary forms in comparison to the analysis only of the water in the pools. The confirmation of the genera by Gram stain showed a different identification profile, in which Naegleria spp. stood out before the genus Acanthamoeba (61.11% and 38.89%, respectively). Conclusion In conclusion, the results of the study confirm the presence of potentially pathogenic isolates from free-living amoebae in swimming pools for collective use that may present risks to public health.