Hybrid process for genotoxics removal from active pharmaceutical ingredients combining organic solvent nanofiltration with polybenzimidazole adsorbents

Active pharmaceutical ingredients (APIs), as most of medicines, are obtained through chemical synthesis, using highly reactive reagents and usually, low levels of reagents, fractions of catalysts, or by-products are present in the final API or drug product as impurities. Some of these impurities have unwanted toxicities, including genotoxicity and carcinogenicity, and therefore related API administration risks for patient’s health has become an increasing concern of pharmaceutical companies, regulatory authorities, patients and doctors. European Medicines Agency (EMA) was the first agency to implement guidelines to control genotoxic impurities (GTIs), followed by the Food and Drug Administration (FDA). Both authorities agreed on setting as “Threshold of Toxicological Concern” (TTC) a limit at 1.5 micrograms per day for known and potential carcinogens [1,2]. Herein we report an approach based on the thermal treatment of a polybenzimidazole polymer providing novel adsorbent properties for genotoxic removal to purify API post-reaction streams. These novel adsorbents were tested for GTIs, such as methyl p-toluenesulfonate, p-toluenesulfonic acid, 4,4-dimethylamino pyridine and ethanesulfonyl chloride, from API solutions of Mometasone furoate (Meta). The current work will present a strategy of a hybrid process combining organic solvent nanofiltration (OSN) of API post-reaction streams with the adsorbers studied. The aim to include an adsorber stage, after the OSN operation, is to polish the retentate API solution for further purification or/and recovery of API lost through the permeate stream. Results will illustrate process efficiency gains. References [1] Teasdale A.; Elder D.; Chang S. J.; Wang S.; Thompson R.; Benz N.; Flores I. H. S., Org. Process Res. Dev. 17, 2013, 221-230. [2] EMEA Guidelines on the “Limits on Genotoxic Impurities”, EMEA/CHMP/QWP/251344/2006, 2006. Acknowledgements: We thank financial support from Fundação para a Ciência e Tecnologia (FCT) through the Project SelectHost (PTDC/QEQ-PRS/4157/2014) and iBB-Institute for Bioengineering and Biosciences (UID/BIO/04565/2013), from Programa Operacional Regional de Lisboa 2020 (Lisboa-01-0145-FEDER-007317) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – Brasil). We thank to Hovione PharmaScience Ltd for supplying the API and technical know-how

Força, qualidade muscular e marcadores de risco cardiometabólico em mulheres idosas

O processo de envelhecimento está associado a um declínio nas funções fisiológicas, refletindo em reduções na qualidade muscular, bem como em alterações de marcadores de risco cardiometabólico. Nesse sentido, o objetivo do estudo foi verificar a associação entre qualidade muscular e marcadores de risco cardiometabólico em mulheres idosas. Trinta mulheres idosas (66,13±5,26 anos, 67,33±12,45 kg, 1,54±0,07 m, 28,20±4,72 IMC) foram submetidas à avaliação da espessura e força musculares do quadríceps, e à análise sanguínea de marcadores de risco cardiometabólico (glicemia, insulina basal, proteína C-reativa, colesterol total, HDL-colesterol, LDL-colesterol, VLDL-colesterol, triglicerídeos, e índice HOMA-IR). Não foram encontradas correlações significativas entre os fenótipos musculares e os marcadores de risco cardiometabólico estudados, mesmo com controle para fatores de confusão. A presente pesquisa indica não haver correlação entre força e qualidade muscular com os marcadores de risco cardiometabólico estudados.The aging process is associated with a decline in physiological functions, including a reduction in muscle quality, as well as changes in cardiometabolic risk factors. Thus, the aim of this study was to verify if a correlation exists between muscle strength and quality and cardiometabolic risk markers in older women. Thirty older women (66.13±5.26 years, 67.33±12.45 kg, 1.54±0.07 m, body mass index: 28.20±4.72) were submitted to the evaluation of muscle thickness and strength and blood analysis of cardiometabolic risk markers (glucose, basal insulin, C-reactive protein, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, and HOMA-IR). No significant correlations were found between muscle phenotypes and markers of cardiometabolic risk, even after adjustment for confounding factors. The present study indicates that muscle strength or quality is not correlated with markers of cardiometabolic risk

Nutritional composition and bioactivity of Umbilicus rupestris (Salisb.)Dandy: An underexploited edible wild plant

The inclusion of edible wild plants in human diet has been receiving an increasing attention, as they represent an easily accessible source of nutrients, vitamins and antioxidants. In this work, the leaves of Umbelicus rupestris (Salisb.) Dandy, an edible species for which only scarce data is available in literature, were thoroughly evaluated for its nutritional profile, chemical characterization and bioactive properties. Being considered a succulent plant, the leaves revealed a very high content of moisture, with several beneficial compounds, including omega-3 polyunsaturated fatty acids, tocopherols and different polyphenols. A total of twelve flavonoids, three phenolic acids and one phenylpropanoid glucoside were identified in the decoction and/or hydroethanolic extracts, with most of them being described for the first time in this plant. Both extracts showed antioxidant activity and potential to inhibit some of the assayed bacteria, while not presenting cytotoxic effects on a non-tumour primary cell culture.The authors are grateful to the Foundation for Science and Technology FCT, Portugal) and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2019). L. Barros, R.C. Calhelha, and A. Fernandes thank national funding by FCT, P.I., through the institutional scientific employment program-contract. For their contracts. This work was also funded by FEDER-Interreg España- Portugal programme through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio

Chemical composition and bioactive properties of the wild edible plant Raphanus raphanistrum L.

Recently, there has been an interest regarding the consumption of wild edible plants in modern diets. However, there is still scarce information about several wild vegetables traditionally consumed. Therefore, this work aims on documenting the nutritional and chemical composition of wild radish (Raphanus raphanistrum L.), as well as its bioactive potential. Results showed that wild radish is a potential source of beneficial compounds, including vitamin E, polyunsaturated fatty acid (particularly α-linolenic acid) and different phenolic compounds, in which fourteen phenolics were identified, with kaempferol-3,7-O-di-rhamnoside being the most abundant. The bioactive potential was exploited using hydroethanolic and decoction extracts. Both proved to inhibit several Gram-positive and Gram-negative bacteria and revealed antioxidant activity, while cytotoxicity against nontumor cell was not observed. In general, results evidence the interest in recovering the use of this wild vegetable as part of a varied diet, which can bring several health benefits.info:eu-repo/semantics/publishedVersio

Effect of photoperiodicity in the pregnancy rate of isogenic rats (F344)

O uso de animais isogênicos apresenta grandes vantagens experimentais, como uniformidade fenotípica e genotípica (reduzindo o número de animais em experimentos) e histocompatibilidade, permitindo, assim, o acúmulo de informações e a repetibilidade dos experimentos. A linhagem isogênica de Rattus norvegicus Fischer 344 existe há 90 anos, entretanto pouco se sabe sobre as razões de seu baixo índice reprodutivo. O presente estudo demonstrou que ratos Fischer F344 são fotorresponsivos quanto à reprodução, tendo seus índices de prenhezes acrescidos com o aumento do fotoperíodo. Os melhores índices são obtidos quando os machos são submetidos a 14 horas de luz e fêmeas a 16 horas de luz, indicando dimorfismo sexual na fotorresponsividade.The use of isogenic animals presents great experimental advantages, as phenotypic and genotypic uniformity (reducing the number of experimental animals) and histocompatibility, thus allowing, the accumulation of information, and the repeatability of the experiments. The isogenic strain of Rattus norvegicus Fischer 344 has existed for 90 years, however the reasons of its low reproductive index are not knew. The present study has demonstrated that Fischer F344 rats are photoresponsive regarding reproduction, having improved its pregnancy index with the increase of the photoperiod. The best indexes were achieved when the males had been submitted to 14 hours of light and females to 16 hours of light, indicating sexual dimorphism in photoresponsivity

Mortalidade em agentes da polícia rodoviária federal: série temporal entre 2001 e 2020

OBJETIVO Descrever e analisar a tendência de mortalidade, por todas as causas, em agentes da polícia rodoviária federal, entre os anos de 2001 e 2020. MÉTODOS Trata-se de um estudo ecológico de séries temporais, baseado em dados oficiais sobre mortalidade registrados no sistema de cadastro nacional da polícia rodoviária federal e de certidões de óbitos do sistema de cadastro federal. Foram coletados os óbitos de agentes que estavam em efetivo exercício entre 2001 e 2020. Realizou-se análise descritiva, calcularam-se proporções e taxas de incidência por 1.000 policiais. Utilizou-se qui-quadrado para análises bivariadas e regressão de Prais-Winsten para análise de tendência. RESULTADOS Ocorreram 346 óbitos (11 por causas indeterminadas), dos quais 146 foram por mortes naturais e 189 não naturais. A maioria das mortes ocorreu em policiais do sexo masculino (n = 333; 96,3%), acima de 35 anos (n = 265; 76,6%), tempo de serviço até 15 anos (n = 185; 53,5%), da região Nordeste e por causas não naturais (n = 189; 56,4%). O número absoluto de óbitos de agentes apresentou tendência decrescente ao longo da série (p = -0,78; IC95% -1,03 – -0,5). Entre as principais causas de morte estão acidentes de trânsito (n = 96; 28,7%), doenças cardiovasculares (n = 58; 17,3%), violência interpessoal (n = 51; 15,2%), suicídio (n = 35; 10,5%) e neoplasias malignas (n = 35; 10,4%). As mortes naturais predominaram entre os agentes com idade entre 51–73 anos (68,3%; IC95% 58,6–76,7) e mais de 26 anos de serviço (64,7%; IC95% 52,7–75,1), já as não naturais, entre a faixa etária de 19–35 anos (87,3%; IC95% 78,0–93,1) e de até 15 anos de serviço (70,2%; IC95% 63,1–76,4). CONCLUSÕES Conclui-se que a tendência das mortes de agentes da polícia rodoviária federal foi decrescente no período. O conhecimento das causas de mortalidade pode auxiliar no desenvolvimento de políticas de prevenção de doenças e proteção à saúde desses policiais.OBJECTIVE To analyze the mortality trend from all causes in Brazilian federal highway police officers from 2001 to 2020. METHODS This is an ecological time-series study based on mortality official data from the Brazilian federal highway police registry system and death certificates from the federal registry system. Deaths of active police officers from 2001 to 2020 were assessed. We performed a descriptive analysis reporting proportions and incidence rates per 1,000 police officers. The chi-square test was used for bivariate analyzes and Prais-Winsten regression was used for trend analysis. RESULTS Among 346 deaths, 146 were from natural and 189 from unnatural causes (11 were from undefined causes). Most deaths occurred among police officers who were men (n = 333; 96.3%), over 35 years old (n = 265; 76.6%), whose service time was up to 15 years (n = 185; 53.5%), living in Northeast Brazil, and from unnatural causes (n = 189; 56.4%). The absolute number of deaths presented a decreasing trend throughout the series (p = -0.78; 95%CI: -1.03 to -0.5). Traffic accidents (n = 96; 28.7%), cardiovascular diseases (n = 58; 17.3%), interpersonal violence (n = 51; 15.2%), suicides (n = 35; 10.5%), and malignant neoplasms (n = 35; 10.4%) were the main causes of death. Most natural deaths occurred among police officers who were 51–73 years old (68.3%; 95%CI: 58.6 to 76.7) and worked more than 26 years (64.7%; 95%CI: 52.7 to 75.1), while most unnatural deaths occurred among officers who were 19–35 years old (87.3%; 95%CI: 78.0 to 93.1) and worked up to 15 years (70.2%; 95%CI: 63.1 to 76.4). CONCLUSION The mortality trend in Brazilian federal highway police officers decreased within the period studied. Understanding mortality causes may help to develop policies for disease prevention and health protection of police officers

Dinámica de fluidos computacionales (CFD) y su uso para analizar la distribucion de gases al interior de instalaciones pecuarias: una revisión de literatura

Currently, one of the most discussed subjects in commercial livestock production is the emission of gases and temperature distribution, associated to climate change and animal welfare, principally with gas as methane (CH4) and ammonia (NH3). Application of computational fluid dynamics (CfD) for predicting the occurrence of these gases, especially in the animal production sector, is becoming increasingly important. Along the years, the versatility, precision and ease of use offered by CfD has caused its greater acceptance by the agricultural and animal engineering community. Therefore, CfD is regularly utilized to solve environmental problems associated to climate control in commercial animal production installations. Due to a better combination between computational simulation in CfD and mathematical modeling, realism of these simulations has become more reliable in recent years. Based on these facts, the goal of this study was to showed the recent studies using commercial Computational fluid Dynamics (CfD) to determinate the behavior and distributions of gases inside animal production installations, showing the advantages and limitations of the technique.Actualmente, uno de los casos de mayor discusión en la producción animal, es la emisión de gases y de distribución de temperatura asociados al cambio climático y al comportamiento animal, principalmente con gases como metano (CH4) y el amoniaco (NH3). La aplicación de la dinámica de los fluidos computacionales (CfD) para predecir el comportamiento de esos gases, especialmente en el sector de producción animal, esta comenzando a ganar gran importancia. A lo largo de los años, la versatilidad, precisión y la facilidad de uso ofrecida por el CfD ha tenido una gran aceptación en la comunidad de la Ingeniería Agrícola y pecuaria en general. Por lo tanto, el CfD es regularmente utilizado para solucionar problemas ambientales asociados a control climático en instalaciones comerciales de producción animal. Debido a la mejor combinación entre la simulación computacional con CfD y modelos matemáticos, situaciones reales se han simulado con mayor confiabilidad en los últimos años. Este trabajo ofrece una revisión del estado del arte acerca de la aplicación de la técnica con CfD para determinar el comportamiento y distribución de gases al interior de instalaciones pecuarias, mostrando las ventajas y limitaciones de la técnica.Incluye referencias bibliográfica

Characterization of whitening toothpastes and their effect on the physical properties of bulk-fill composites

Objective: To characterize activated charcoal and 2% hydrogen peroxide-based toothpastes and investigate their effects on roughness, color change, and gloss of bulk-fill composite resin. Methodology: Composite resin specimens (Aura Bulk Fill, SDI) were subjected to 5,000 brushing cycles with regular toothpaste (Colgate Total 12, [RT]), activated charcoal toothpaste (Bianco Dental Carbon, [AC]), or hydrogen peroxide-containing toothpaste (Colgate Luminous White Advanced, [HP]), with or without coffee exposure. The pH, particle characterization by scanning electron microscopy (SEM), and weight% of solid particles in the toothpaste were assessed. Roughness (Ra) was evaluated using a surface profile-measuring device, color change (∆Eab/∆E00) by reflectance spectrophotometer, and gloss unit (GU) by glossmeter. Kruskal–Wallis, Dunn, Friedman, and Nemenyi tests were used, and the correlation coefficient test was performed between Ra and GU (α=0.05). Results: RT presented a higher Ra after brushing and did not change after staining with coffee; moreover, the ∆Eab/∆E00 values were higher for RT than HP. Regarding gloss, AC and HP obtained higher values compared to RT. A significant negative correlation between gloss and Ra was found for RT exposed to coffee. All toothpastes had a neutral pH; however, RT had the largest percentage of solids by weight. SEM images showed particles of many sizes: irregular shape (RT), more regular particles (AC), and spherical clusters (HP). Although surface roughness, color change, and gloss may compromise the longevity of restorations, the whitening toothpastes tested did not promote more morphology changes than regular toothpastes