Cromatografia preparativa: caracterização e purificação de produtos e impurezas com aplicação na indústria de APIs

Neste trabalho efectuou-se o desenvolvimento de métodos de purificação de princípios activos farmacêuticos utilizando a cromatografia preparativa em coluna (eluição batch). Por motivos de confidencialidade as amostras tiveram a denominação de Amostra Projecto A, Amostra Projecto B, Amostra Projecto C e Amostra 2 - Projecto A. Estudou-se a performance de coluna para cada projecto utilizando colunas pré-preparadas e colunas preparadas com a tecnologia DAC (Dynamical Axial Compression). Elaborou-se o procedimento experimental de enchimento de colunas preparativas sob compressão axial. As impurezas isoladas por cromatografia preparativa foram sujeitas a caracterização HPLC e LC-MS. Com colunas pré-preparadas, obteve-se para a amostra do projecto A um rendimento de 70,59% e relativamente à amostra projecto B obteve-se u, rendimento de 15,39%. Relativamente à impureza isolada da amostra do projecto A, o estudo por HPLC revelou 98,69% de pureza, quanto à impureza da amostra projecto B obteve-se 88,80% de pureza. A impureza da amostra do projecto A exibiu por LC-MS a massa de 467,15 enquanto que a impureza da amostra do projecto B obteve 503,31. O enchimento de colunas preparativas sob pressão axial dinâmica foi realizado numa coluna de dimensão 260 X 25 mm, onde 76,60% da coluna foi compactada com o material de enchimento SepTech ST150-C18, 10 µm. A coluna foi testada com a impureza isolada do projecto A. Isolou-se o pico referente à impureza, e por LC-MS verificou-se que a impureza foi isolada eficientemente com 97,20& de pureza e massa 467,15 como indicado anteriormente. Em relação à preparação de colunas com a tecnologia DAC concluímos que, neste caso, é mais vantajoso realizar o enchimento das colunas do que efectuar a compra de colunas pré-preparadas. Com estes resultados pode-se concluir que a cromatografia preparativa é um método eficaz no isolamento de impurezas de APIs (Active Pharmaceutical Ingredients) face a métodos de purificação clássicos que foram realizados previamente noutros estudos. Com futuros desenvolvimentos e investimentos, facilmente poderá tornar-se num método de purificação indispensável na Indústria de Química Fina

A visão da mulher asiática no século XVI através do olhar de Duarte Barbosa e de Tomé Pires

Dissertação de Mestrado em Estudos Portugueses Multidisciplinares apresentada à Universidade Abert

O nível de dependência da nicotina é um fator de risco independente para o câncer: um estudo caso-controle

BACKGROUND: Less than 20% of lifetime smokers will ever develop cancer. Smoking habits characteristics, particularly the level of nicotine dependence level, were not fully evaluated as a marker of risk. METHODS: Case-control study of voluntary patients prospectively enrolled in a smoking cessation program in a cancer hospital. For each cancer case, patients of the same age and sex were selected. The Beck Depression Inventory, an instrument for the diagnosis of depressive mood and clinical depression, and the Fagerström Test Questionnaire, a questionnaire that has a good correlation with nicotine levels, used to determine the degree of dependence on nicotine, were applied. Age on admission to the study, sex, and number of pack-years were also evaluated. RESULTS: From May 1999 to May 2002, 56 cancer patients (case) and 85 matching controls (control) were identified in the population studied. There was no difference regarding pack-years. Fagerström Test Questionnaire was significantly higher in patients with cancer (7.5 ± 1.9) compared to controls (6.3 ± 2.0). We found a Fagerström Test Questionnaire >; 7 in 73.2% of the cancer cases versus 43.5% of the controls (p=0.001). The proportion of depressed patients was higher in the cancer group (37.5% x 17.6%). Logistic regression adjusted for age and tobacco consumption disclosed that Fagerström Test Questionnaire score >; 7 has an odds ratio for cancer of 3.45 (95% CI 1.52 - 7.83, p = 0.003). CONCLUSION: Fagerström Test Questionnaire higher than 7 was identified as a risk factor for cancer in smokers with similar tobacco consumption.OBJETIVO: Menos de 20% dos fumantes crônicos desenvolverá cancer. As características do hábito de fumar, particularmente o nível de dependência à nicotina, não foram avaliadas inteiramente como um marcador do risco. MÉTODOS: Estudo caso-controle de pacientes voluntários, registrados prospectivamente em um programa de cessação de tabagismo em um hospital de cancer. Para cada caso de cancer, pacientes da mesma idade e sexo foram selecionados. O inventário de depressão de Beck, um instrumento validado para diagnóstico de estado depressivo e depressão clínica e o questionário de tolerância de Fagerstron , que é usado para determinar o grau de dependência e tem boa correlação com níveis de nicotina, foram aplicados. Idade na admissão ao estudo, sexo, número de maços-anos fumados foram avaliados também. RESULTADOS: De maio de 1999 a maio de 2002, 56 pacientes de câncer (caso) e 85 controles pareados (controle) foram identificados na população estudada . Não houve diferença quanto ao número de maços-ano. O questionário de tolerância de Fagerstron foi significativamente mais elevado nos pacientes com câncer (7.5 ± 1.9) comparado aos controles (6.3 ± 2.0). Encontramos um questionário de tolerância de Fagerstron >; 7 em 73.2% dos casos de câncer, contra 43.5% dos controles (p=0.001). A proporção de pacientes deprimidos foi mais elevada no grupo do cancer (37.5% x 17.6%). A regressão logística, ajustada para a idade e o consumo do tabaco, apontou que uma contagem de questionário de tolerância de Fagerstron >; 7 tem uma razão de chance para câncer de 3.45 (CI 95% 1.52 - 7.83, p = 0.003). CONCLUSÃO: Resultado no questionário de tolerância de Fagerstron maior que 7 foi identificado como um fator de risco para cancer em fumantes com consumo similar do tabaco

El estado nutricional y los hábitos alimentarios de niños de edad preescolar

Contexto: A prevalência da obesidade infantil continua a aumentar em todo o Mundo. As suas consequências são dramáticas, estando-lhe associada uma maior probabilidade de morte prematura e incapacidade na vida adulta. Este é um dos maiores desafios de saúde para o século XXI. Objetivo: Classificar o estado nutricional das crianças de idade pré-escolar a frequentar os jardins-de-infância selecionados; Caracterizar os hábitos alimentares das crianças de idade pré-escolar a frequentar os jardins-de-infância selecionados. Metodologia: Estudo não-experimental do tipo descritivo e transversal desenvolvido num centro de saúde da zona do concelho de Sintra, no âmbito do Programa de Saúde Escolar. A amostra é constituída por 300 crianças. Resultados: 154 crianças pertencem ao género masculino, 146 ao feminino; 140 crianças têm 3 anos de idade e 160 têm 4 anos; 92 crianças (30.6%) têm excesso de peso. Destas, 41 apresentam pré-obesidade (13.6%) e 51 obesidade (17.0%). Os alimentos mais consumidos pertencem ao grupo alimentar da carne, peixe e ovos. Conclusão: A prevalência de crianças com excesso de peso na amostra estudada é elevada. Verifica-se uma distorção na representatividade dos produtos consumidos, existindo um consumo exagerado de produtos do grupo da carne, peixe e ovos.Context: The prevalence of childhood obesity continues to increase worldwide. Its consequences are dramatic, and are associated with a higher probability of premature death and disability in adult life. This situation is so alarming that it is considered one of the greatest health challenges in the 21st century. Goals: To classify the nutritional status of preschool-age children attending selected kindergartens; To characterize the dietary habits of preschool-age children attending selected kindergartens. Methods: A non-experimental, descriptive and cross-sectional study developed in a health care centre of the Municipality of Sintra, within the scope of the School Health Programme. The sample consisted of 300 children. Results: 154 children were male, 146 were female; 140 children were 3 years old and 160 were 4 years old; 92 Children (30.6%) were overweight. Of these, 41 children were pre-obese (13.6%) and 51 were obese (17%). The most consumed foods belonged to the “meat, fish and eggs” food group. Conclusions: The prevalence of overweight children in the study sample was high. An imbalance was observed in the representation of the consumed products, due to an excessive consumption of products from the “meat, fish and eggs” food group.Introducción: La prevalencia de la obesidad infantil sigue aumentando en todo el mundo. Sus consecuencias son dramáticas, ya que se asocia a una mayor probabilidad de muerte prematura y discapacidad en la edad adulta. Esto se considera como uno de los mayores retos de la salud para el siglo XXI. Objetivos: Clasificar el estado nutricional de los niños de edad preescolar que acuden a los jardines de infancia selecionados; Caracterizar los hábitos alimentarios de los niños de edad preescolar que acuden a los jardines de infancia selecionados. Métodos: Estudio no experimental, descriptivo y transversal, desarrollado en un centro de salud de Sintra, en el programa de salud escolar. La muestra estuvo formada por 300 niños. Resultados: Se trata de 154 niños y 146 niñas; 140 niños tienen 3 años y 160 tienen 4 años; 92 niños (30,6%) tienen sobrepeso. De estos, 41 tienen preobesidad (13,6%) y 51 obesidad (17,0%). Los alimentos más consumidos pertenecen al grupo de las carnes, pescados y huevos. Conclusiones: La prevalencia de niños con sobrepeso en nuestra muestra es alta. Asimismo, se ha comprobado que existe una representación distorsionada en la rueda de los alimentos, pues hay un consumo excesivo de productos que pertenecen al grupo de las carnes, pescados y huevos

Are cellulose nanofibrils safe for biomedical applications?

Nanomedicine is based on the application of nanotechnologies into the medical field to advance and improve diagnostics, prevention and treatment of human disease. While its expansion has been enormous in the last years, its progress must go hand in hand with nanosafety, i.e., with the safety evaluation of nanomaterials in an early phase of its development or application into a product. Cellulose appears as a natural and readily available material, which fits within the supply-demand chain: ecological, abundant and low cost. Particularly, cellulose nanofibrils (CNF) show great mechanical strength and high water-uptake capability and have the ability to form translucent structures with high elasticity and selective permeability, which make them attractive e.g., as constituents of surgical dressings and membranes for bone regeneration. Bacterial nanocellulose is already being used, but CNF produced from plants are also finding potential to be applied in tissue engineering and regenerative medicine. However, CNF may bring more toxicological concerns than the bacterial type, due to impurities associated with the chemical and mechanical processes used to produce them or due to their different physicochemical properties that may underlie unforeseen biological effects. The main objective of this work was to evaluate the safety of two different CNFs, through the analysis of their cytotoxic, genotoxic and epigenetic effects in human osteoblasts. The CNFs were obtained from the same raw material – industrial bleached Eucalyptus globulus kraft pulp - by two different methods: TEMPO-mediated oxidation and enzymatic hydrolisis. The physicochemical properties of the CNF gels obtained, including fibrillation yield, degree of polymerization and size were evaluated. The CNF cytotoxicity was assessed by the MTT assay and the genotoxicity by the cytokinesis-block micronucleus assay; their epigenetic effects were evaluated through gene expression analysis of the DNA methytransferases genes, DNMT1 and DMNT3b, responsible for the cellular methylation pattern, using qRT-PCR. The results obtained for the several endpoints were integrated in order to contribute to the characterization of the potential toxic effects of these new CNF in an early phase of their lifecycle. This knowledge will be relevant to decide whether these CNF may be further developed for applications in the nanomedicine field, or shall be modified to give rise to safer CNF.ToxApp4NanoCELFI , 2018-2021 - PTDC/SAU-PUB/32587/2017; ToxOmics - Centro de Investigação em Toxicogenómica e Saúde Humana - UID/BIM/00009/2013N/

Shear Bond Strength Of Metallic Brackets Bonded With A New Orthodontic Composite

Aim: The aim of this study was to assess the shear bond strength of orthodontic brackets in different enamel surfaces using the Transbond Plus Color Change composite (TPCC-3M Unitek), and to analyze the Adhesive Remnant Index (ARI). Methods: Seventy-two human premolars were divided into six groups (n = 12), as follows: Group 1(control) - Transbond XT conventional; in Groups 2 to 6, TPCC was used under the following enamel treatment conditions: phosphoric acid and XT-primer; Transbond Plus Self-Etching Primer (TPSEP); phosphoric acid only; phosphoric acid, XT-primer and saliva; and TPSEP and saliva, respectively. Twenty-four hours after bonding, the brackets were debonded with an Instron machine at a crosshead speed of 0.5 mm/min, and ARI was evaluated by using a stereoscopic magnifying glass. Results: The mean shear strength values (MPa) for Groups 1 to 6 were 24.6, 18.7, 17.5, 19.7, 17.5 and 14.8, respectively. Data were submitted to ANOVA and Tukey’s test (? = 0.05). Group 1 had significantly higher shear bond strength values than Groups 3, 5, and 6 (p 0.05). No statistically significant differences (p > 0.05) were found between Groups 2, 3, 4, 5 and 6. Conclusions: Bracket bonding using TPCC showed adequate adhesion for clinical use, and the type of enamel preparation had no influence.8276-8

A potential method for comparing instrumental analysis of volatile organic compounds using standards calibrated for the gas phase

In this paper we report a method for the comparative analysis of volatile organic compounds (VOCs) at physiologically representative concentrations by different analytical methods Standard aqueous solutions of acetone, ethanol, methanol, 1-propanol, 2-propanol and acetaldehyde were prepared by adding a specific mass of compound to a known volume of water, calculated using published Henry's law constants for individual compounds. Headspace concentrations are thus known from established partitioning from dilute aqueous phase in accordance with Henry's law. Selected Ion Flow Tube Mass Spectrometry (SIFT-MS), Proton Transfer Reaction Mass Spectrometry (PTR-MS), and Gas Chromatography–Mass Spectrometry (GC–MS) coupled to thermal desorption have been used to study and evaluate the performance of the instruments in the analysis of these VOCs. These analytical techniques have been widely used in the identification and quantification of trace concentrations of VOCs in biological samples. Quantitative determination of VOC concentration was achieved and the performance of the instruments compared with one another. Calibration curves are given within the range 101–103 ppbv

Lack of Correlation between Periodontitis and Renal Dysfunction in Systemically Healthy Patients

Objectives: The aim of this study was to assess a suggested association between periodontitis and renal insufficiency by assaying kidney disease markers. Methods: Variables used to diagnose periodontitis were: (i) probing pocket depth (PPD), (ii) attachment loss (AL), (iii) bleeding on probing (BOP), (iv) plaque index (PI) and (v) extent and severity index. Blood and urine were collected from 60 apparently healthy non-smokers (men and women), consisting of a test group of 30 subjects with periodontitis (age 46±6 yrs) and a control group of 30 healthy subjects (age 43±5 yrs). Kidney function markers (urea, creatinine, uric acid and albumin contents) were measured in the serum and urine. Also, the glomerular filtration rate was estimated from creatinine clearance, from the abbreviated Modification of Diet in Renal Disease formula and from the albumin: creatinine ratio in a 24-h sample of urine. Results: It was found that the control group had a greater mean number of teeth than the test group and that the two groups also differed in PPD, AL, BOP and PI, all these variables being higher in the test group (P=0.006). For the extent and severity index of both PPD and AL, the test group had much higher medians of both extent and severity than the control group (P=0.001). With regard to kidney function, none of the markers revealed a significant difference between the control and test groups and all measured values fell within the reference intervals. Conclusions: It is proposed that severe periodontitis is not associated with any alteration in kidney function