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.

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).

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.

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.

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.

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.