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1.
Chem Biodivers ; : e202401247, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896778

RESUMEN

As part of our continuous research for the discovery of bioactive compounds against Trypanosoma cruzi and Leishmania infantum, the alkaloid (6aS)-dicentrine (1) was oxidized to afford (6aS,6S)- (2) and (6aS,6R)- (3) dicentrine-N-oxides. Evaluation of the cytotoxicity against NCTC cells indicated that 2 and 3 are non-toxic (CC50 > 200 µM) whereas 1 demonstrated CC50 of 52.0 µM. Concerning T. cruzi activity against amastigotes, derivatives 2 and 3 exhibited EC50 values of 9.9 µM (SI > 20.7) and 27.5 µM (SI > 7.3), respectively, but 1 is inactive (EC50 > 100 µM). Otherwise, when tested against L. infantum amastigotes, 1 and 3 exhibited EC50 values of 10.3 µM (SI = 5.0) and 12.7 µM (SI > 15.7), respectively, being 2 inactive (EC50 > 100 µM). Comparing the effects of positive controls benznidazol (EC50 = 6.5 µM and SI > 30.7) and miltefosine (EC50 = 10.2 µM and SI = 15.0), it was observed a selective antiparasitic activity to diastereomers 2 and 3 against T. cruzi and  L. infantum. Considering stereochemical aspects, it was suggested that the configuration of the new stereocenter formed after oxidation of 1 played an important role in the bioactivity against amastigotes of both tested parasites.

2.
Bioorg Chem ; 147: 107408, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38678776

RESUMEN

This study aimed to assess the antiprotozoal efficacy of dicentrine, an aporphine alkaloid isolated from Ocotea puberula, against amastigote forms of Leishmania (L.) infantum. Our findings reveal that dicentrine demonstrated a notable EC50 value of 10.3 µM, comparable to the positive control miltefosine (EC50 of 10.4 µM), while maintaining moderate toxicity to macrophages (CC50 of 51.9 µM). Utilizing an in silico methodology, dicentrine exhibited commendable adherence to various parameters, encompassing lipophilicity, water solubility, molecule size, polarity, and flexibility. Subsequently, we conducted additional investigations to unravel the mechanism of action, employing Langmuir monolayers as models for protozoan cell membranes. Tensiometry analyses unveiled that dicentrine disrupts the thermodynamic and mechanical properties of the monolayer by expanding it to higher areas and increasing the fluidity of the film. The molecular disorder was further corroborated through dilatational rheology and infrared spectroscopy. These results contribute insights into the role of dicentrine as a potential antiprotozoal drug in its interactions with cellular membranes. Beyond elucidating the mechanism of action at the plasma membrane's external surface, our study sheds light on drug-lipid interface interactions, offering implications for drug delivery and other pharmaceutical applications.


Asunto(s)
Antiprotozoarios , Antiprotozoarios/farmacología , Antiprotozoarios/química , Relación Estructura-Actividad , Membrana Celular/efectos de los fármacos , Aporfinas/farmacología , Aporfinas/química , Relación Dosis-Respuesta a Droga , Lauraceae/química , Estructura Molecular , Leishmania infantum/efectos de los fármacos , Pruebas de Sensibilidad Parasitaria , Animales
3.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38324622

RESUMEN

Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research.


Asunto(s)
Metabolómica , Programas Informáticos , Reproducibilidad de los Resultados , Flujo de Trabajo , Metabolómica/métodos , Espectrometría de Masas/métodos , Cromatografía Liquida/métodos
4.
Colloids Surf B Biointerfaces ; 234: 113747, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38219639

RESUMEN

This study investigates the interaction between sakuranetin, a versatile pharmaceutical flavonoid, and monolayers composed of unsaturated phospholipids, serving as a surrogate for cell membranes. The phospholipids were 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE). We conducted a series of experiments to comprehensively investigate this interaction, including surface pressure assessments, Brewster angle microscopy (BAM), and polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). Our findings unequivocally demonstrate that sakuranetin interacts with these phospholipids, expanding the monomolecular films. Notably, regarding POPC, the presence of sakuranetin led to a reduction in stability and a decline in surface elasticity, which can likely be attributed to intricate molecular rearrangements at the interface. The visual evidence of aggregations in BAM images reinforces the interactions substantiated by PM-IRRAS, highlighting sakuranetin's interaction with the polar and nonpolar regions of POPC. However, it is worth noting that these aggregations do not appear to contribute significantly to the viscosity of the mixed film, and our investigations did not reveal any substantial hysteresis. In contrast, when examining POPE, we observed a minor reduction in thermodynamic stability, indicative of fewer rearrangements within the monolayer. This notion was further reinforced by the limited presence of aggregations in the BAM images. Sakuranetin also increased the rigidity of the lipid monolayer; nevertheless, the monolayer remained predominantly elastic, facilitating easy re-spreading on the surface, especially for the first lipid. PM-IRRAS analysis unveiled interactions between sakuranetin and POPE's polar and nonpolar segments, compellingly explaining the observed monolayer expansion. Taken together, our data suggest that sakuranetin was more effectively incorporated into the monomolecular layer of POPE, indicating that membranes comprised of POPC might exhibit a greater degree of interaction in the presence of this pharmacologically active compound.


Asunto(s)
Fosfolípidos , Fitoalexinas , Agua , Agua/química , Propiedades de Superficie , Fosfolípidos/química , Flavonoides
5.
J Chem Inf Model ; 64(7): 2565-2576, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38148604

RESUMEN

American Trypanosomiasis, also known as Chagas disease, is caused by the protozoan Trypanosoma cruzi and exhibits limited options for treatment. Natural products offer various structurally complex metabolites with biological activities, including those with anti-T. cruzi potential. The discovery and development of prototypes based on natural products frequently display multiple phases that could be facilitated by machine learning techniques to provide a fast and efficient method for selecting new hit candidates. Using Random Forest and k-Nearest Neighbors, two models were constructed to predict the biological activity of natural products from plants against intracellular amastigotes of T. cruzi. The diterpenoid andrographolide was identified from a virtual screening as a promising hit compound. Hereafter, it was isolated from Cymbopogon schoenanthus and chemically characterized by spectral data analysis. Andrographolide was evaluated against trypomastigote and amastigote forms of T. cruzi, showing IC50 values of 29.4 and 2.9 µM, respectively, while the standard drug benznidazole displayed IC50 values of 17.7 and 5.0 µM, respectively. Additionally, the isolated compound exhibited a reduced cytotoxicity (CC50 = 92.8 µM) against mammalian cells and afforded a selectivity index (SI) of 32, similar to that of benznidazole (SI = 39). From the in silico analyses, we can conclude that andrographolide fulfills many requirements implemented by DNDi to be a hit compound. Therefore, this work successfully obtained machine learning models capable of predicting the activity of compounds against intracellular forms of T. cruzi.


Asunto(s)
Productos Biológicos , Enfermedad de Chagas , Cymbopogon , Diterpenos , Nitroimidazoles , Trypanosoma cruzi , Animales , Enfermedad de Chagas/tratamiento farmacológico , Diterpenos/farmacología , Diterpenos/metabolismo , Productos Biológicos/metabolismo , Mamíferos
6.
Eur J Med Chem ; 248: 115074, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36623331

RESUMEN

Chagas disease, after more than a century after its discovery, is still a major public health problem. It is estimated that approximately 10 million people worldwide are infected with T. cruzi. However, the situation is more critical in Latin America and other regions where the disease is endemic. The largest number of cases occurs in Brazil, Argentina, and Mexico as more than 100 million people in these regions are located in areas with a high risk of contamination by the vector. The need for new therapeutic alternatives is urgent, as the available drugs have severe limitations such as low efficacy and high toxicity. From this scenario, in this work, we employed the virtual screening technique using cruzain and BDF2 as key biological targets for the survival of the parasite. Our objective was to identify potential inhibitors of T. cruzi trypomastigotes, which could be considered drug candidates against Chagas disease. For this, we employed different in silico methodologies and the obtained results were corroborated using in vitro biological assays. For the VS studies, a database containing synthetic compounds was simulated at the binding site of cruzain and BDF2. In addition, pharmacophoric models were constructed in the initial phases of VS, as well as other advanced analyses (molecular dynamics simulations, calculations of binding free energy, and ADME prediction) were carried out and the results allowed the selection of potential inhibitors of T. cruzi. Based on the obtained data, 32 different compounds commercially available were subjected to biological tests against the trypomastigote form of T. cruzi. As result, 11 of those compounds displayed significant activity against T. cruzi and can be considered potential candidates for the treatment of Chagas disease.


Asunto(s)
Enfermedad de Chagas , Tripanocidas , Trypanosoma cruzi , Humanos , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Simulación de Dinámica Molecular , Sitios de Unión , Dominios Proteicos , Tripanocidas/farmacología , Tripanocidas/uso terapéutico , Tripanocidas/química
7.
Curr Top Med Chem ; 23(3): 159-213, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36515019

RESUMEN

BACKGROUND: Chagas disease (American Trypanosomiasis) is classified by the World Health Organization (WHO) as one of the seventeen neglected tropical diseases (NTD), affecting, mainly, several regions of Latin America. INTRODUCTION: However, immigration has expanded the range of this disease to other continents. Thousands of patients with Chagas disease die annually, yet no new therapeutics for Chagas disease have been approved, with only nifurtimox and benznidazole available. Treatment with these drugs presents several challenges, including protozoan resistance, toxicity, and low efficacy. Natural products, including the secondary metabolites found in plants, offer a myriad of complex structures that can be sourced directly or optimized for drug discovery. METHODS: Therefore, this review aims to assess the literature from the last 10 years (2012-2021) and present the anti-T. cruzi compounds isolated from plants in this period, as well as briefly discuss computational approaches and challenges in natural product drug discovery. Using this approach, more than 350 different metabolites were divided based on their biosynthetic pathway alkaloids, terpenoids, flavonoids, polyketides, and phenylpropanoids which displayed activity against different forms of this parasite epimastigote, trypomastigote and more important, the intracellular form, amastigote. CONCLUSION: In this aspect, there are several compounds with high potential which could be considered as a scaffold for the development of new drugs for the treatment of Chagas disease-for this, more advanced studies must be performed including pharmacokinetics (PK) and pharmacodynamics (PD) analysis as well as conduction of in vivo assays, these being important limitations in the discovery of new anti-T. cruzi compounds.


Asunto(s)
Enfermedad de Chagas , Tripanocidas , Trypanosoma cruzi , Humanos , Tripanocidas/química , Enfermedad de Chagas/tratamiento farmacológico , Nifurtimox/farmacología , Nifurtimox/uso terapéutico , Descubrimiento de Drogas
8.
Proc Natl Acad Sci U S A ; 119(32): e2120777119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35917341

RESUMEN

Tipping elements are nonlinear subsystems of the Earth system that have the potential to abruptly shift to another state if environmental change occurs close to a critical threshold with large consequences for human societies and ecosystems. Among these tipping elements may be the Amazon rainforest, which has been undergoing intensive anthropogenic activities and increasingly frequent droughts. Here, we assess how extreme deviations from climatological rainfall regimes may cause local forest collapse that cascades through the coupled forest-climate system. We develop a conceptual dynamic network model to isolate and uncover the role of atmospheric moisture recycling in such tipping cascades. We account for heterogeneity in critical thresholds of the forest caused by adaptation to local climatic conditions. Our results reveal that, despite this adaptation, a future climate characterized by permanent drought conditions could trigger a transition to an open canopy state particularly in the southern Amazon. The loss of atmospheric moisture recycling contributes to one-third of the tipping events. Thus, by exceeding local thresholds in forest adaptive capacity, local climate change impacts may propagate to other regions of the Amazon basin, causing a risk of forest shifts even in regions where critical thresholds have not been crossed locally.


Asunto(s)
Sequías , Bosque Lluvioso , Cambio Climático , Árboles
9.
Environ Sci Technol ; 56(14): 9924-9935, 2022 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-35801846

RESUMEN

The Amazon rainforest suffers increasing pressure from anthropogenic activities. A key aspect not fully understood is how anthropogenic atmospheric emissions within the basin interact with biogenic emissions and impact the forest's atmosphere and biosphere. We combine a high-resolution atmospheric chemical transport model with an improved emissions inventory and in-situ measurements to investigate a surprisingly high concentration of ozone (O3) and secondary organic aerosol (SOA) 150-200 km downwind of Manaus city in an otherwise pristine forested region. We show that atmospheric dynamics and photochemistry determine a gross production of secondary pollutants seen in the simulation. After sunrise, the erosion of the nocturnal boundary layer mixes natural forest emissions, rich in biogenic volatile organic compounds, with a lofted pollution layer transported overnight, rich in nitrogen oxides and formaldehyde. As a result, O3 and SOA concentrations greater than ∼47 ppbv and 1.8 µg m-3, respectively, were found, with maximum concentrations occurring at 2 pm LT, 150-200 km downwind of Manaus city. These high concentrations affect a large primary forested area of about 11,250 km2. These oxidative areas are under a NOx-limited regime so that changes in NOx emissions from Manaus have a significant impact on O3 and SOA production.


Asunto(s)
Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Bosques , Ozono/análisis
10.
Cien Saude Colet ; 26(12): 6059-6068, 2021 Dec.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-34909998

RESUMEN

The objective was to estimate the prevalence and factors associated with prehypertension and hypertension among health workers who work in high-complexity services for critically-ill and chronic patients. An epidemiological, cross-sectional study was carried out with 490 health workers in the macroregional region of Northern Minas Gerais, Brazil. The dependent variable blood pressure (BP) was categorized as normal BP, prehypertension and hypertension. Multinomial Logistic Regression was used for the multiple analysis. The prevalence of arterial hypertension was 21.8% and that of prehypertension was 25.9%. The chances of developing arterial hypertension and prehypertension were higher in male professionals, aged ≥40 years, in civil servant workers and those who were obese or overweight. The use of continuous medication and night shift work were associated with hypertension and prehypertension, respectively. The prevalence of arterial hypertension in the group of workers was lower than that of the Brazilian population. It is necessary to carry out studies with workers from this group and investments are required in preventive measures that encourage a change to a healthy lifestyle.


Objetivou-se estimar a prevalência e fatores associados à pré-hipertensão e hipertensão arterial entre trabalhadores de saúde que atuam em setores de alta complexidade para pacientes críticos e crônicos. Foi realizado um estudo epidemiológico, transversal com 490 trabalhadores de saúde da macrorregional do norte de Minas Gerais, Brasil. A variável dependente pressão arterial foi categorizada em normal, pré-hipertensão e hipertensão. Para análise múltipla, foi utilizada a Regressão Logística Multinomial. A prevalência da hipertensão arterial foi de 21,8% e da pré-hipertensão foi de 25,9%. As chances de se desenvolver a hipertensão arterial e a pré hipertensão foram maiores nos profissionais do sexo masculino, com idade ≥40 anos, em trabalhadores com vínculo empregatício concursado e naqueles obesos ou com sobrepeso. O uso de medicamento contínuo e o trabalho no turno noturno estiveram associados à hipertensão e pré-hipertensão, respectivamente. A prevalência de hipertensão arterial no grupo de trabalhadores foi menor do que a da população brasileira. São necessários estudos com trabalhadores desse grupo e investimentos em medidas preventivas e que incentivem a mudança para um estilo de vida saudável.


Asunto(s)
Hipertensión , Prehipertensión , Estudios Transversales , Personal de Salud , Humanos , Hipertensión/epidemiología , Masculino , Prehipertensión/epidemiología , Factores de Riesgo
11.
Enferm. foco (Brasília) ; 12(6): 1070-1076, dez. 2021. ilus
Artículo en Portugués | LILACS, BDENF | ID: biblio-1368640

RESUMEN

Objetivo: compreender os significados que cercam o tema "valorização profissional" e suas implicações no agir e pensar dos sujeitos envolvidos. Método: trata-se de um estudo exploratório de abordagem qualitativa ancorado, principalmente, na teoria do Interacionismo Simbólico de Blumer e nos postulados da Análise do Conteúdo de Bardin. A coleta de dados ocorreu mediante entrevistas semiestruturadas, com profissionais e estudantes das várias áreas de atuação da enfermagem, cuja pergunta central foi "O que é valorização profissional para você?". Os diálogos foram gravados e posteriormente transcritos, analisados e categorizados por meio do software Atlas.ti. Resultados: a partir do conteúdo das falas, pôde-se agrupá-las em categorias, a saber: engajamento político, feedback social, investimento de recursos, relação interpessoal e realização profissional. Todas essas categorias foram elencadas devido à relação direta, segundo os entrevistados, com o tema valorização profissional uma vez que se evidenciou a grande importância desses fatores para se instigar o sentimento do sentir-se valorizado. Considerações finais: em consonância com as teorias empregadas, pôde-se ratificar a interferência das experiências e desafios profissionais nas concepções e juízos acerca do mote central deste estudo. Ademais, evidenciou-se o enfoque concedido ao engajamento político e ao feedback social como formas eficazes de se alcançar a valorização. (AU)


Objective: To understand the meanings surrounding the theme "professional valorization" and its implications for the actions and thinking of the subjects involved. Methods: This is an exploratory study with a qualitative approach anchored, mainly, in the theory of Symbolic Interactionism by Blumer and in the postulates of Bardin's Content Analysis. Data collection took place through semi-structured interviews, with professionals and students from the various areas of nursing practice, whose central question was "What is professional valorization for you?". The dialogues were recorded and later transcribed, analyzed and categorized using the Atlas.ti software. Results: Based on the statements, it was possible to group them into categories, namely: political engagement, social feedback, investment of resources, interpersonal relationships and professional achievement. All of these categories were listed due to the direct relationship with the theme of professional valorization since the great importance of these factors was evidenced to instigate the feeling of feeling valued. Conclusion: According to the theories discussed, it was possible to ratify the interference of professional experiences and challenges in the conceptions and judgments about the central motto of this study. Moreover, the focus on political engagement and social feedback was shown to be effective ways of achieving appreciation. (AU)


Objetivo: Comprender los significados que rodean el tema "valorización profesional" y sus implicaciones para las acciones y el pensamiento de los sujetos involucrados. Métodos: Se trata de un estudio exploratorio con enfoque cualitativo anclado, principalmente, en la teoría del Interaccionismo Simbólico de Blumer y en los postulados del Análisis de Contenido de Bardin. La recolección de datos se realizó a través de entrevistas semiestructuradas, con profesionales y estudiantes de las distintas áreas de la práctica de enfermería, cuya pregunta central fue "¿Qué es para ti la valorización profesional?". Los diálogos fueron grabados y sistematizado utilizando el software Atlas.ti. Resultados: Fue posible agrupar el contenido en categorías, a saber: compromiso político, retroalimentación social, inversión de recursos, relaciones interpersonales y logros profesionales. Todas estas categorías fueron enumeradas debido a la relación directa, con el tema de la valoración profesional desde que se hizo evidente su importancia para instigar el sentimiento de apreciación. Conclusion: En línea con las teorías, se logró ratificar la interferencia de experiencias y desafíos profesionales en las concepciones y juicios sobre el lema central de este estudio. Además, se demostró que el enfoque en el compromiso político y la retroalimentación social son formas efectivas de lograr el reconocimiento. (AU)


Asunto(s)
Enfermería , Deseabilidad Social , Interaccionismo Simbólico , Compromiso Laboral
12.
Ciênc. Saúde Colet. (Impr.) ; 26(12): 6059-6068, Dez. 2021. tab, graf
Artículo en Inglés, Portugués | LILACS | ID: biblio-1350483

RESUMEN

Resumo Objetivou-se estimar a prevalência e fatores associados à pré-hipertensão e hipertensão arterial entre trabalhadores de saúde que atuam em setores de alta complexidade para pacientes críticos e crônicos. Foi realizado um estudo epidemiológico, transversal com 490 trabalhadores de saúde da macrorregional do norte de Minas Gerais, Brasil. A variável dependente pressão arterial foi categorizada em normal, pré-hipertensão e hipertensão. Para análise múltipla, foi utilizada a Regressão Logística Multinomial. A prevalência da hipertensão arterial foi de 21,8% e da pré-hipertensão foi de 25,9%. As chances de se desenvolver a hipertensão arterial e a pré hipertensão foram maiores nos profissionais do sexo masculino, com idade ≥40 anos, em trabalhadores com vínculo empregatício concursado e naqueles obesos ou com sobrepeso. O uso de medicamento contínuo e o trabalho no turno noturno estiveram associados à hipertensão e pré-hipertensão, respectivamente. A prevalência de hipertensão arterial no grupo de trabalhadores foi menor do que a da população brasileira. São necessários estudos com trabalhadores desse grupo e investimentos em medidas preventivas e que incentivem a mudança para um estilo de vida saudável.


Abstract The objective was to estimate the prevalence and factors associated with prehypertension and hypertension among health workers who work in high-complexity services for critically-ill and chronic patients. An epidemiological, cross-sectional study was carried out with 490 health workers in the macroregional region of Northern Minas Gerais, Brazil. The dependent variable blood pressure (BP) was categorized as normal BP, prehypertension and hypertension. Multinomial Logistic Regression was used for the multiple analysis. The prevalence of arterial hypertension was 21.8% and that of prehypertension was 25.9%. The chances of developing arterial hypertension and prehypertension were higher in male professionals, aged ≥40 years, in civil servant workers and those who were obese or overweight. The use of continuous medication and night shift work were associated with hypertension and prehypertension, respectively. The prevalence of arterial hypertension in the group of workers was lower than that of the Brazilian population. It is necessary to carry out studies with workers from this group and investments are required in preventive measures that encourage a change to a healthy lifestyle.


Asunto(s)
Humanos , Masculino , Prehipertensión/epidemiología , Hipertensión/epidemiología , Estudios Transversales , Factores de Riesgo , Personal de Salud
13.
Chem Biodivers ; 18(4): e2001022, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33635585

RESUMEN

One new aporphine, dicentrine-ß-N-oxide (1), together with five related known alkaloids dehydrodicentrine (2), predicentrine (3), N-methyllaurotetanine (4), cassythicine (5), and dicentrine (6) were isolated from the leaves of Ocotea puberula (Lauraceae). Antiprotozoal activity of the isolated compounds was evaluated in vitro against trypomastigote forms of Trypanosoma cruzi. Among the tested compounds, alkaloid 1 exhibited higher potential with EC50 value of 18.2 µM and reduced toxicity against NCTC cells (CC50 >200 µM - SI>11.0), similar to positive control benznidazole (EC50 of 17.7 µM and SI=10.7). Considering the promising results of dicentrine-ß-N-oxide (1) against trypomastigotes, the mechanism of parasite death caused by this alkaloid was investigated. As observed, this compound reached the plasma membrane electric potential directly after 2 h of incubation and triggered mitochondrial depolarization, which probably leads to trypomastigote death. Therefore, dicentrine-ß-N-oxide (1), reported for the first time in this work, can contribute to future works for the development of new trypanocidal agents.


Asunto(s)
Aporfinas/farmacología , Membrana Celular/efectos de los fármacos , Ocotea/química , Extractos Vegetales/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Aporfinas/química , Aporfinas/aislamiento & purificación , Línea Celular , Membrana Celular/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Tripanocidas/química , Tripanocidas/aislamiento & purificación
14.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 13: 1167-1171, jan.-dez. 2021. tab
Artículo en Inglés, Portugués | LILACS, BDENF | ID: biblio-1255130

RESUMEN

Objetivo: Identificar a influência da espiritualidade no trabalho dos profissionais de saúde da oncologia de dois hospitais do Norte de Minas Gerais. Método: o estudo trata-se de uma pesquisa quantitativa, transversal e descritiva. Questão norteadora: influência da espiritualidade no trabalho dos profissionais de saúde da oncologia. Resultado: nenhum profissional de saúde é considerado totalmente sem espiritualidade, sendo que 15,9% se consideram muito religiosa e 84,1% se consideram moderadamente religiosa; e quando se perguntou: o quanto se considera pessoa espiritualizada? 15,9% se consideram muito espiritualizada e 84,1% se consideram moderadamente espiritualizada. Conclusão: a presente pesquisa denota-se uma tendência baixa quanto à frequência com que esses profissionais buscam por um apoio religioso. Constatou-se, também, a escassez de serviços de apoio religioso no âmbito hospitalar


Objective:To identify the influence of spirituality on the work of oncology health professionals from two hospitals in the North of Minas Gerais. Method: the study is a quantitative, cross-sectional and descriptive research. Guiding question: influence of spirituality on the work of oncology health professionals. Results: no health professional is considered totally without spirituality, 15.9% consider themselves very religious and 84.1% consider themselves moderately religious; and when asked: how much do you consider yourself a spiritual person? 15.9% consider themselves very spiritualized and 84.1% consider themselves moderately spiritualized. In the interpretation of the results it is noticed that the participants do not know how to distinguish religiosity from spirituality, because it was exactly the same result. Conclusion: the present research shows a low tendency as to the frequency with which these professionals seek for a religious support. It was also verified the shortage of religious support services in the hospital


Objetivo: Identificar la influencia de la espiritualidad en el trabajo de los profesionales de salud de la oncología de dos hospitales del Norte de Minas Gerais. Método: el estudio se trata de una investigación cuantitativa, transversal y descriptiva. Cuestión orientadora: influencia de la espiritualidad en el trabajo de los profesionales de salud de la oncología. Resultado:ningún profesional de salud es considerado totalmente sin espiritualidad, siendo que el 15,9% se considera muy religioso y el 84,1% se considera moderadamente religiosa; y cuando se preguntó: o cuánto se considera persona espiritualizada? El 15,9% se considera muy espiritualizada y el 84,1% se considera moderadamente espiritualizada. Conclusión: la presente investigación denota una tendencia baja en cuanto a la frecuencia con que estos profesionales buscan un apoyo religioso. Se constató también la escasez de servicios de apoyo religioso en el ámbito hospitalario


Asunto(s)
Humanos , Masculino , Femenino , Servicio de Oncología en Hospital , Personal de Salud , Espiritualidad , Estudios Transversales
15.
ACM arq. catarin. med ; 49(3): 12-22, 06/10/2020.
Artículo en Portugués | LILACS-Express | LILACS | ID: biblio-1354305

RESUMEN

Introdução: A partir da década de 80, inferiu-se universitários como fator de risco para o alcoolismo. A área da saúde parecem estar mais propensa aos abusos na ingestão de álcool Objetivo: Identificar a prevalência do consumo de álcool em estudantes de cursos da saúde de uma instituição pública de ensino superior da cidade de Montes Claros-MG. Métodos: Trata-se de um estudo quantitativo, do tipo transversal e descritivo. A amostra foi constituída de 150 universitários dos cursos de Medicina e Enfermagem da Universidade Estadual de Montes Claros-MG. Na coleta de dados foram utilizados o questionário sócio demográfico, o Teste de Identificação de Desordens Devido ao Álcool (AUDIT), o Teste de Triagem do Envolvimento com Álcool, Cigarro e Outras Substâncias (ASSIST), o Inventário de Expectativas e Crenças Pessoais Acerca do Álcool (IECPA), e a Escala de Satisfação com o Suporte Social (ESSS). Para análise dos dados, aplicou-se o programa SPSS, versão 19.0. Resultados: A maioria dos universitários foram classificados na zona de baixo risco (72,7%), a maior parte deles (73,4%) fazem uso ocasional de outras substâncias, 64,7% apresentam baixa expectativa com relação ao alcoolismo, 52% dos universitários apresentam alto suporte social. Discussão: Padrões de consumo de álcool altos estão relacionados a um nível de satisfação social mais baixo. Conclusão: Foi encontrado um número expressivo de indivíduos com risco alto e alta vulnerabilidade, cabe a universidade investir em prevenção primária para conter esses índices.


Introduction: From the 80's on, university students were inferred as a risk factor for alcoholism. Healthcare seems to be more prone to alcohol abuse. Objective: To identify a prevalence of alcohol in students of health courses of a public institution of higher education in the city of Montes Claros-MG. Methods: This is a quantitative, cross-sectional and descriptive study. The sample consisted of 150 university students from the Medicine and Nursing courses of the State University of Montes Claros-MG. On the date the demographic test was sent, the Alcohol Identifying Disorder Test (AUDIT), the Alcohol Involvement Screening Test, ASSIST, the Alcohol Personal Expectation and Belief Inventory (IECPA), and the Social Support Satisfaction Scale (ESSS). For the analysis of the data, the SPSS program, version 19.0 is applied. Results: Most of the university students were classified in the low-risk zone (72.7%), most of them (73.4%), the fashion of other substances, 64.7% had an expectation regarding alcoholism, 52% of university students have high social support. Discussion: High alcohol consumption patterns are related to a lower level of social satisfaction. Conclusion: An expressive number of individuals with high risk and high vulnerability was found, which should be one of the main sources of information.

16.
Bioorg Chem ; 101: 103978, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32534347

RESUMEN

In the present work, the oxoaporphine alkaloid dicentrinone was isolated, for the first time, from leaves of Ocotea puberula (Lauraceae). This alkaloid exhibited antiparasitic activity against trypomastigote forms of Trypanosoma cruzi (IC50 of 16.4 ± 1.7 µM), similar to the positive control benznidazole (IC50 of 18.7 ± 4.1 µM), reduced mammalian cytotoxicity (CC50 > 200 µM), and a selectivity index (SI) higher than 12. These results were correlated with the effects observed using cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), in Langmuir monolayers. Dicentrinone was incorporated in the films, submitted to lateral compression, and characterized by tensiometry. As observed in compression-decompression and time-stability curves, dicentrinone expanded the lipid monolayers, decreased the compressional modulus of the film, and reduced the stability of the monolayer. Brewster Angle Microscopy and interfacial Infrared Spectroscopy showed that dicentrinone causes the monolayers to be segregated in phases, and to increase the number of gauche/trans conformers ratio for the lipid acyl methylene groups, indicating configurational disorder. As a result, dicentrinone caused a disturbance in the cell membrane models, altering the physicochemical properties of the lipid surface such as thermodynamic, rheological, morphological, and structural aspects. These results can be useful to understand the interactions between dicentrinone and lipid biological surfaces at the molecular level.


Asunto(s)
Alcaloides/química , Aporfinas/química , Productos Biológicos/uso terapéutico , Membrana Celular/efectos de los fármacos , Lauraceae/química , Hojas de la Planta/química , Trypanosoma cruzi/efectos de los fármacos , Animales
17.
Ciênc. Saúde Colet. (Impr.) ; 25(1): 199-209, jan. 2020. tab
Artículo en Portugués | LILACS | ID: biblio-1055775

RESUMEN

Resumo Objetivou-se identificar os fatores associados à personalidade hardiness em profissionais de saúde atuantes em serviços hospitalares que atendem a pacientes críticos. Estudo epidemiológico, transversal e analítico, realizado com 469 profissionais de saúde. Como instrumento, utilizou-se a Escala Hardiness (EH) associada a um questionário para investigar as condições sociodemográficas, ocupacionais e de saúde. Foi realizada a análise descritiva e bivariada por meio do teste qui-quadrado e modelo múltiplo através de regressão logística múltipla, utilizando o teste Hosmer Lemeshow e PseudoR2, estimando razão das chances (odds ratio). A classificação dos escores totais na EH evidenciou preponderância de moderado hardiness (48,4%). A chance de alto hardiness entre profissionais com estilo de vida fantástico regular ou ruim reduziu em 74% quando comparado aos considerados muito bons e excelentes. Também esteve aumentada entre os profissionais que não tiveram licença/afastamento, que apresentavam alta satisfação por compaixão no trabalho, baixo estresse e baixo burnout. A personalidade hardiness influência direta e indiretamente a saúde e o bem-estar do profissional de saúde atuante em serviços hospitalares que atendem a pacientes críticos.


Abstract This study aimed to identify factors associated with the hardy personality in health professionals working in hospital services that treat critically ill patients. This is an epidemiological, cross-sectional, and analytical study conducted with 469 health professionals. We used the Hardiness Scale (HS), coupled with a questionnaire to investigate sociodemographic, occupational, and health conditions. A descriptive and bivariate analysis was performed using the chi-square test and the multiple model through multiple logistic regression, using the Hosmer-Lemeshow and PseudoR2 tests, estimating odds ratios. The classification of total scores in HS showed prevailing moderate hardiness (48.4%). Professionals with a fair or poor fantastic lifestyle (FL) were 74% less likely to show high hardiness than those with very good and excellent FL. Also, professionals who were not on leave, who had high satisfaction with compassion at work, low stress, and low burnout were more likely to show high hardiness. The hardy personality, directly and indirectly, influences the health and well-being of health professionals working in hospital services that treat critically ill patients.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Adulto Joven , Personalidad , Personal de Hospital/psicología , Adaptación Psicológica , Cuidados Críticos , Resiliencia Psicológica , Estrés Laboral/psicología , Estudios Epidemiológicos , Estudios Transversales , Persona de Mediana Edad
18.
Cien Saude Colet ; 25(1): 199-209, 2020 Jan.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-31859868

RESUMEN

This study aimed to identify factors associated with the hardy personality in health professionals working in hospital services that treat critically ill patients. This is an epidemiological, cross-sectional, and analytical study conducted with 469 health professionals. We used the Hardiness Scale (HS), coupled with a questionnaire to investigate sociodemographic, occupational, and health conditions. A descriptive and bivariate analysis was performed using the chi-square test and the multiple model through multiple logistic regression, using the Hosmer-Lemeshow and PseudoR2 tests, estimating odds ratios. The classification of total scores in HS showed prevailing moderate hardiness (48.4%). Professionals with a fair or poor fantastic lifestyle (FL) were 74% less likely to show high hardiness than those with very good and excellent FL. Also, professionals who were not on leave, who had high satisfaction with compassion at work, low stress, and low burnout were more likely to show high hardiness. The hardy personality, directly and indirectly, influences the health and well-being of health professionals working in hospital services that treat critically ill patients.


Objetivou-se identificar os fatores associados à personalidade hardiness em profissionais de saúde atuantes em serviços hospitalares que atendem a pacientes críticos. Estudo epidemiológico, transversal e analítico, realizado com 469 profissionais de saúde. Como instrumento, utilizou-se a Escala Hardiness (EH) associada a um questionário para investigar as condições sociodemográficas, ocupacionais e de saúde. Foi realizada a análise descritiva e bivariada por meio do teste qui-quadrado e modelo múltiplo através de regressão logística múltipla, utilizando o teste Hosmer Lemeshow e PseudoR2, estimando razão das chances (odds ratio). A classificação dos escores totais na EH evidenciou preponderância de moderado hardiness (48,4%). A chance de alto hardiness entre profissionais com estilo de vida fantástico regular ou ruim reduziu em 74% quando comparado aos considerados muito bons e excelentes. Também esteve aumentada entre os profissionais que não tiveram licença/afastamento, que apresentavam alta satisfação por compaixão no trabalho, baixo estresse e baixo burnout. A personalidade hardiness influência direta e indiretamente a saúde e o bem-estar do profissional de saúde atuante em serviços hospitalares que atendem a pacientes críticos.


Asunto(s)
Adaptación Psicológica , Cuidados Críticos , Estrés Laboral/psicología , Personalidad , Personal de Hospital/psicología , Resiliencia Psicológica , Adulto , Estudios Transversales , Estudios Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
19.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 12: 559-565, jan.-dez. 2020. tab
Artículo en Inglés, Portugués | LILACS, BDENF | ID: biblio-1096920

RESUMEN

Objetivo: analisar o perfil dos enfermeiros-docentes da Graduação em Enfermagem de uma universidade pública. Método: estudo descritivo, tipo survey, com dados extraídos dos currículos de 57 docentes, vinculados ao Departamento de Enfermagem da Universidade Estadual de Montes Claros em exercício no mês de maio/2017. Resultados: a maioria se graduou em Instituições de Ensino Superior públicas; 12 anos de experiência na educação superior; 15 anos de experiência profissional; titulação de mestrado e/ou doutorado e com publicações em periódicos QUALIS com menor relevância. Utilizaram abordagem quantitativa, na área de saúde do adulto. Conclusão: a experiência e titulação qualificam os docentes para a assistência e/ou o ensino e a opção pelas áreas temáticas refletem preocupação com a qualidade do cuidado. Recomenda-se a inserção dos docentes em Grupos de Pesquisa e os estudantes na Iniciação Científica, importantes estratégias de qualificação da profissão para proporcionar maior visibilidade, reconhecimento e consolidação da Enfermagem como ciência


Objective: to analyze the profile of nurse-teachers of undergraduate nursing at a public university. Method: a quantitative-descriptive-crosssectional study, with data extracted from the curricula of 57 teachers linked to the nursing department of a public university in Minas Gerais, from 2012 to 2018. Results: the teachers have on average 12 years of experience in Higher education, 15 years of professional experience, most have graduated from public institutions, have master's and doctorate degrees. Regarding the areas of knowledge most covered in the publications, the prevalence of the adult health area was identified, with quantitative approach studies and in less relevant QUALIS journals. Conclusion: The results showed that nurse-teachers are concerned with teaching performance and sought for proper training in stricto sensu postgraduate programs, but need to emphasize acting as a researcher in order to provide greater visibility, recognition and consolidation of nursing as science


Objetivo: analizar el perfil de enfermeras-docentes de enfermeria de pregados en una universidad publica. Método: un estudio cuantitativodescriptivo- transversal, con datas extraidos de los planes de estudio de 57 docentes vinculados al departamento de enfermeria de una universidad publica en Minas Gerais, de 2012 a 2018. Resultados: los docentes tienen en promedio 12 anos de experiencia en Educacion superior, 15 anos de experiencia profesional, la mayoria se han graduado de instituciones publicas, tienen maestrias y doctorados. Con respecto a las areas de conocimiento mas cubiertas en las publicaciones, se identifico la prevalencia del area de salud de adultos, con estudios de abordaje cuantitativo y en revistas QUALIS menos relevantes. Conclusión: Los resultados mostrar que las enfermeras-docentes estan preocupadas por el desempeno docente y buscaron una capacitacion adecuada em los programas de posgrado estrictos, pero deben enfatizar la actuacion como investigadores para proporcionar una mayor visibilidad,reconocimiento y consolidacion de la enfermeria como ciencia


Asunto(s)
Humanos , Universidades , Educación en Enfermería , Docentes de Enfermería , Práctica Profesional
20.
J Pharm Pharmacol ; 71(12): 1871-1878, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31595517

RESUMEN

OBJECTIVE: This work describes the isolation of anti-Leishmania amazonensis metabolites from Saururus cernuus (Saururaceae). Additionally, ultrastructural changes in promastigotes were evidenced by electron microscopy. METHODS: The MeOH extract from the leaves of S. cernuus was subjected to bioactivity-guided fractionation. Anti-L. amazonensis activity of purified compounds was performed in vitro against promastigote and amastigote forms. KEY FINDINGS: Bioactivity-guided fractionation of the MeOH extract from the leaves of S. cernuus afforded two related tetrahydrofuran dineolignans: threo,threo-manassantin A (1) and threo,erythro-manassantin A (2). Compounds 1 and 2 displayed activity against promastigotes (EC50 of 35.4 ± 7.7 and 17.6 ± 4.2 µm, respectively) and amastigotes (EC50 of 20.4 ± 1.9 and 16.0 ± 1.1 µm, respectively), superior to that determined for the positive control miltefosine (EC50 of 28.7 ± 3.5 µm). Reduced cytotoxicity for host cells was observed for both compounds. Additionally, ultrastructural changes in promastigotes leading to an alteration of structural morphology were observed, as evidenced by electron microscopy. Furthermore, these compounds altered the morphology and physiology of the plasmatic membrane of L. amazonensis. CONCLUSIONS: The obtained results indicated that dineolignans 1 and 2 could be considered as a scaffold for the design of novel and selective drug candidates for the treatment of leishmaniasis.


Asunto(s)
Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Leishmaniasis/tratamiento farmacológico , Lignanos/farmacología , Saururaceae/química , Animales , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Furanos/química , Furanos/aislamiento & purificación , Furanos/farmacología , Leishmaniasis/parasitología , Lignanos/química , Lignanos/aislamiento & purificación , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Hojas de la Planta
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