1,720,976 research outputs found

    Determinação das curvas de absorção, perfis de dissolução e estabelecimento de correlação in vitro-in vivo por métodos in silico utilizando o GastroPlusTM e o DDDPlusTM

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    The use of computer programs to predict drug absorption in humans and to simulate dissolution profiles has become a valuable tool in the pharmaceutical area. The objective of this study was to use in silico methods through software GastroPlusTM and DDDPlusTM to simulate drug absorption curves and dissolution profiles, and to establish in vitro-in vivo correlations (IVIVCs). The work presented herein is divided into five chapters and includes the drugs ketoprofen, pyrimethamine, metronidazole, fluconazole, carvedilol and doxazosin. In Chapter 1, simulated plasma curves for ketoprofen matrix tablets are presented and IVIVC was established. The use of simulated intrinsic dissolution tests for pyrimethamine and metronidazole as a tool for biopharmaceutics classification is detailed in Chapter 2. In Chapter 3, simulation of plasma curves for fluconazole capsules with different dissolution profiles is demonstrated as a tool for biowaiver. IVIVC studies were also conducted for carvedilol immediate-release tablets from dissolution profiles in Chapter 4. Chapter 5 covers the application of simulated dissolution tests for development of doxazosin extended-release formulations. Simulation of plasma curves and IVIVC using the software GastroPlusTM as well as intrinsic dissolution tests and dissolution profiles using the software DDDPlusTM proved to be a tool of wide application in predicting biopharmaceutical characteristics of drugs and formulations, allowing the reduction of time and costs of experimental laboratory work.O uso de programas de computador para prever a absorção de fármacos em humanos e simular perfis de dissolução tem se tornado uma ferramenta bastante valiosa na área farmacêutica. O objetivo deste trabalho foi utilizar métodos in silico por meio dos programas de computador GastroPlusTM e DDDPlusTM para simular curvas de absorção de fármacos, perfis de dissolução e estabelecer correlações in vitro-in vivo (CIVIVs). O material aqui apresentado é constituído por cinco capítulos incluindo os fármacos cetoprofeno, pirimetamina, metronidazol, fluconazol, carvedilol e doxazosina. No capítulo 1 são apresentadas curvas plasmáticas simuladas para comprimidos matriciais de cetoprofeno, sendo estabelecida a CIVIV. A utilização de simulações de ensaios de dissolução intrínseca para os fármacos pirimetamina e metronidazol como uma ferramenta para classificação biofarmacêutica é detalhada no capítulo 2. No capítulo 3, a simulação de curvas plasmáticas a partir de cápsulas de fluconazol contendo diferentes perfis de dissolução é demonstrada como uma ferramenta para bioisenção. Estudos de CIVIV foram também realizados para comprimidos de liberação imediata de carvedilol a partir dos perfis de dissolução no capítulo 4. Já o capítulo 5 trata da aplicação de simulações de ensaios de dissolução para o desenvolvimento de formulações de liberação prolongada de doxazosina. As simulações das curvas plasmáticas, assim como a CIVIV, obtidas com o auxílio do programa GastroPlusTM, além dos ensaios de dissolução intrínsica e os perfis de dissolução obtidos por meio do uso do programa DDDPlusTM apresentaram-se como ferramentas de grande aplicação na previsão de características biofarmacêuticas sobre os fármacos e formulações, permitindo redução de tempo e custo com trabalho experimental em laboratório

    Vaping Additives Affect Lateral Organization and Functionality of Lung Surfactant Model Systems

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    Recent use of THC-based vapes has led to an outbreak of respiratory health issues. While the pathology is unresolved, common symptoms point to dysfunction of the lung surfactant (LS). This is a lipid-protein monofilm situated at the air-water interface in alveolar sacs, which acts to lower surface tension, preventing lung collapse during respiration. Inhaled substances that reach the alveoli will encounter LS. Certain vape additives have been identified as potential causative agents, these being tetrahydrocannabinol and cannabidiol, commonly found in THC products, as well as vitamin E and its derivative vitamin E acetate. The lipophilic nature of these additives may allow them to partition into the monofilm, wherein they could interact with lipids to disrupt proper function. The aim of this thesis was to use model surfactants to better understand the interactions between vaping additives and the primary lipid components of lung surfactant. These films were made up of phosphatidylcholines, phosphatidylglycerols, and cholesterol. Additionally, the clinical surfactant BLES was also used and compared to the model systems. BLES is used in surfactant replacement therapy, making it a good physiological counterpart to the simple model films studied. Surface activity of the films were measured using a Langmuir-Blodgett trough which allowed for compression and expansion of the films, mimicking respiration. Changes to the lateral organization of the films was conducted with Brewster angle microscopy. Visualization of BLES was also carried out with atomic force microscopy, which allowed for higher resolution images of the surfactant’s molecular architecture. Vape additives were found to destabilize domain formations in most systems, often accompanied by fluidization of the film. The effects on BLES provided a unique insight into the mechanistic action of additive induced surfactant dysfunction. Crucial multilayer structures that form on the surface of the film during compression were abolished in the presence of vitamin E acetate, reducing the surfactants ability to maintain a low surface tension. The Langmuir-Blodgett trough has demonstrated to be useful for studying in vitro interactions between lipids and vape additives. With further optimization, this method may be used to predict in vivo effects of vape additives

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Studies on antimicrobial and antioxidant properties of phosvitin hydrolysates produced by high hydrostatic pressure combined with enzymatic hydrolysis

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    Phosvitin (PV) is a metal binding protein in egg yolk with unique amino acid composition (more than 55% serine). Due to a high proportion of phosphorylated serine residues, PV shows metal chelating, antioxidant and antimicrobial activities. The use of PV, however, in nutra- or pharmaceutical application has been restricted mainly due to the formation of insoluble complexes with divalent metal ions in the gastrointestinal tract. The PV hydrolysates (PVH) that are hydrolyzed by proteases may solve the problem and increase their applications without compromising the PV’s functional properties. There are many attempts to produce the PVH. However, the yield of the PVH is low due to the PV’s negative charges causing the resistance to digestive enzymes. The present technology of the high hydrostatic pressure combined with enzymatic hydrolysis (HHP-EH) is a new method to increase the enzyme efficiency. The present study of the HHP-EH shows a higher degree of hydrolysis containing more peptides with Mw< 3 kDa compared to atmospheric pressure (AP). PV Hydrolysis with Alcalase (Alc) under HHP resulted in the highest degree of hydrolysis (31.3%). The PVH treated by Alc and Trypsin (Try) obtained from both HHP and AP treatments showed superior iron chelation capacity (69-73%). Alc-PVH produced by HHP-EH displayed significantly greater reducing power (3.5 μM Trolox equivalent/mg) than AP-PVH (1.3 μM Trolox equivalent/mg). In the second study, a combination of specific IgY (100 μg/mL) and PVH-Alc-HHP (1 mg/mL) as an anti-microbial agent was found to be the most efficient to control the foodborne Enterotoxigenic Escherichia coli (ETEC) K88 and K99 in vitro. The synergistic anti-microbial activities of IgY and PVH may support their potential application in feed supplementation to prevent microbial contamination and infectious diseases. In the third study, there is limited information available on the quantification of PV. The double antibody sandwich ELISA (DAS-ELISA) and biotinylated DAS-ELISA developed has a PV detection range of 5.6 – 90 µg/mL and 2.5 – 40 ng/mL, respectively. The biotinylated DAS-ELISA is a superior method for PV quantification regarding accuracy and sensitivity. This highly efficient PV detection method may recuperate the performance of the existing protein assay methods as well as facilitate future research on PV bioactivities and applications

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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