Preparation and scale up of extended-release tablets of bromopride

A reprodutibilidade do processo de fabricação de comprimidos e o controle das suas propriedades farmacotécnicas depende da otimização dos aspectos de formulação e dos parâmetros de processo. O planejamento de experimentos como o Desenho de Experimentos (DOE) pode ser utilizado para acelerar a produção desta formulação, em particular, para a obtenção de comprimidos de liberação prolongada. Formulações de bromoprida são comercializadas sob a forma de péletes de liberação prolongada, o que torna o produto caro e de difícil fabricação. O objetivo deste estudo foi preparar novas formulações de bromoprida de liberação prolongada na forma de comprimidos e desenvolver modelos matemáticos visando ao escalonamento destas formulações, controlando o peso e a dureza dos comprimidos durante a fabricação, de acordo com a 34ª Edição da USP. Estudos de DOE foram realizados utilizando o software Minitab(tm). Diferentes combinações de excipientes foram avaliadas visando à obtenção dos comprimidos de liberação prolongada de bromoprida. No estudo de scale-up, coletaram-se e mediu-se a influência das variações nos parâmetros da máquina de compressão. Processaram-se os dados obtidos pelo software Minitab (tm), gerando equações matemáticas aptas para a previsão do comportamento de compactação do pó em escala industrial. Os comprimidos obtidos apresentavam características adequadas em termos de liberação sustentada, sendo a cinética de liberação estabelecida utilizando modelos matemáticos, indicando que esta formulação pode ser uma substituta aos péletes de bromoprida atualmente comercializados.Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE) can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm) software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm) software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed

Composition and fungitoxicity of essential oil of citronella grass as affected by organic fertilization

O objetivo deste trabalho foi avaliar a influência da adubação orgânica sobre o teor e a composição do óleo essencial de capim citronela (Cymbopogon nardus), bem como a fungitoxicidade desse óleo ao crescimento micelial dos fungos Didymella bryoniae, Colletotrichum gloeosporioides e Amphobotrys ricini. A extração do óleo essencial foi realizada por hidrodestilação, a partir de plantas cultivadas em quatro doses de adubação orgânica (0, 3, 6 e 9 kg de esterco bovino curtido por cova), e a identificação dos constituintes químicos foi conduzida por cromatografia gasosa/espectrometria de massas. Para avaliar a inibição do crescimento micelial, o experimento foi instalado no delineamento inteiramente casualizado, em arranjo fatorial. Foram testadas sete alíquotas do óleo essencial (0, 5, 10, 15, 20, 25 e 30 μL), em cinco épocas de avaliação, com quatro repetições. O teor de óleo essencial do capim citronela não foi afetado pela adubação orgânica, e o óleo essencial do capim citronela apresentou 24 compostos químicos, entre estes monoterpenos e sesquiterpenos, com maior concentração dos compostos citronelal, β‑citronelol, geraniol e elemol. O óleo essencial do capim citronela apresenta maior efeito de inibição a Amphobotrys ricini, em comparação aos fungos Didymella bryoniae e Colletotrichum gloeosporioides.The objective of this work was to evaluate the influence of organic fertilization on the content and composition of the essential oil of citronella grass (Cymbopogon nardus), as well as to assess the fungitoxicity of this oil to the mycelial growth of the fungi Didymella bryoniae, Colletotrichum gloeosporioides, and Amphobotrys ricini. The extraction of the essential oil was done by hydrodistillation in plants cultivated with four doses of organic fertilizer (0, 3, 6, and 9 kg matured cattle manure per hole), and the identification of the chemical compounds was done by gas chromatography/mass spectroscopy. To evaluate the inhibition of mycelial growth, the experiment was installed in a completely randomized design in a factorial arrangement. Seven aliquots of essential oil were tested (0, 5, 10, 15, 20, 25, and 30 μL) in five evaluating times, with four replicates. The contents of the essencial oil in citronella grass were note affected by organic fertilization, and the oil includes 24 chemical compounds, among these monoterpenes and sesquiterpenes, with higher concentrations of the compounds citronellal, β‑citronellol, geraniol, and elemol. The essential oil of citronella grass has higher inhibition effect on Amphobotrys ricini, when compared to the fungi Didymella bryoniae e Colletotrichum gloeosporioides

Desafios e Oportunidades da Equipe Multidisciplinar na Saúde Pública: Enfoque em Neonatologia e Tratamentos Farmacológicos

Este artigo tem por objetivo discutir os desafios e oportunidades da equipe multidisciplinar na saúde pública, com enfoque em neonatologia e tratamentos farmacológicos. Tal pesquisa trata-se de uma revisão integrativa de literatura, as buscas foram realizadas nas bases de dados SCIELO, LILACS e Google Acadêmico, entre os meses de junho e julho de 2023. Foram usados os descritores em saúde, retirados dos Decs: Saúde Pública; Equipe Multiprofissional; Neonatologia e Tratamento Farmacológico. Os critérios de inclusão foram apenas artigos de revista, em português, publicados dentro do recorte temporal de 2016 e 2023. Como critério de exclusão, estudos repetidos, de acesso pago e fora do escopo. Durante a triagem, apenas 12 estudos não foram eliminados, estes compuseram a amostra final. Com base na amostra, foi demostrado que coordenar diferentes especialidades para cuidar dos recém-nascidos demanda uma comunicação clara, equidade no acesso a recursos e superação das limitações em diagnósticos e tratamentos específicos para neonatos. No entanto, essa abordagem também abre oportunidades significativas. A integração de conhecimentos e habilidades pode levar a tratamentos mais abrangentes e personalizados, pesquisa avançada, promoção da saúde e educação para pais e cuidadores. Conclui-se que, as equipes de saúde tem suas maiores dificuldades relacionadas a fragilidade dos pacientes, diagnósticos imprecisos, disponibilidade de recursos, integração entre equipes, prevenções de infecções, falta de medicamentos, falta de formulações pediátricas, entre outros. Porém, suas oportunidades giram em torno da pesquisa e inovação, da abordagem holística, integração de conhecimentos, educação e redução da mortalidade infantil

Análise genética de características produtivas e reprodutivas em populações multirraciais de bovinos leiteiros

The objective of this work was to determine whether the random regression model using linear splines (RRMLS) is suitable to estimate the genetic parameters for productive and reproductive traits of a multiple-breed dairy cattle population, as well as to investigate the effect of the genetic group of the progeny on the genetic merit of the sire. The multiple-trait model (MTM) and the RRMLS with one knot fitted for every genetic group were used to obtain the genetic parameters. Records of 1/2 Holstein + 1/2 Gyr (1/2HG), 5/8 Holstein + 3/8 Gyr (5/8HG), and 3/4 Holstein + 1/4 Gyr (3/4HG) crossbreed dams were considered. The RRMLS showed better fitting. The additive and residual variances estimated by the MTM and the RRMLS were similar. Heritability varied from 0.20 to 0.33 for age at first calving, from 0.09 to 0.22 for first lactation length, and from 0.15 to 0.35 for first lactation 305-day milk yield, according to the genetic composition of the dams. The RRMLS is suitable to estimate the genetic parameters for productive and reproductive traits of multiple-breed dairy cattle populations. The genetic merit of the sires is affected by the genetic group of the progeny by which they are evaluated.O objetivo deste trabalho foi verificar se o modelo de regressão aleatória com polinômios lineares do tipo spline (MRAPLS) é adequado para estimar os parâmetros genéticos de características produtivas e reprodutivas em uma população multirracial de bovinos leiteiros, bem como investigar o efeito do grupo genético da progênie sobre o mérito genético do touro. Foram utilizados o modelo multicaracterístico (Mult) e o MRAPLS com nós ajustados aos grupos genéticos, para obtenção dos parâmetros genéticos. Foram considerados os registros de vacas 1/2 Holandesa + 1/2 Gir (1/2HG), 5/8 Holandesa + 3/8 Gir (5/8HG) e 3/4 Holandesa + 1/4 Gir (3/4HG). O MRAPLS apresentou os melhores ajustes. As variâncias aditivas e residuais estimadas por Mult e MRAPLS foram semelhantes. As herdabilidades variaram de 0,20 a 0,33 para idade ao primeiro parto, de 0,09 a 0,22 para duração da primeira lactação e de 0,15 a 0,35 para produção de leite em até 305 dias na primeira lactação, de acordo com a composição genética das vacas. O MRAPLS é adequado para estimar parâmetros genéticos de características produtivas e reprodutivas em populações multirraciais de bovinos leiteiros. O mérito genético do touro é influenciado pelo grupo genético da progênie por meio do qual ele é avaliado

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

IntroductionSARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators.MethodsA sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array.ResultsIn the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester.Discussion and conclusionFrom an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost