1,720,954 research outputs found
An Alternative Pathway for the Synthesis of Glycerol Phenylbutyrate
Full text linkImpact Factor: 2.1Fil: Suchetti, Laura. Ministerio de Ciencia y Tecnología de la Provincia de Córdoba. Departamento de Química, Argentina.Fil: Foray, Gabriela. Ministerio de Ciencia y Tecnología de la Provincia de Córdoba. Departamento de Química, Argentina.Fil: Tempesti Tomas C. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica, Argentina.Fil: Tempesti Tomas C. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-Química de Córdoba, Argentina.Fil: Ferrayoli, Carlos. Ministerio de Ciencia y Tecnología de la Provincia de Córdoba. Departamento de Química, Argentina.Hyperammonemia is a life-threatening condition which can affect patients at any age. In pediatric patients, hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle deficiencies or organic acidemias. Glycerol phenylbutyrate (GPB) is an orphan drug used in the treatment of hyperammonemia. GPB is a triglyceride composed of three phenylbutyric acid (PBA) molecules esterified to a glycerol molecule, which is synthesized through the acyl chloride route using thionyl chloride as an acylating agent. In this work we have developed an alternative synthesis method to obtain GPB directly under ambient conditions and avoiding the use of chlorinated solvents. Moreover, the use of carbodiimides as coupling agents, instead of thionyl chloride, allowed the conversion to the GPB in higher yields and with higher purity, without the need for column purification. We present a methodology that allows the production of GPB in a simple, efficient and environmentally and human health friendly way.info:eu-repo/semantics/publishedVersionFil: Suchetti, Laura. Ministerio de Ciencia y Tecnología de la Provincia de Córdoba. Departamento de Química, Argentina.Fil: Foray, Gabriela. Ministerio de Ciencia y Tecnología de la Provincia de Córdoba. Departamento de Química, Argentina.Fil: Tempesti Tomas C. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica, Argentina.Fil: Tempesti Tomas C. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-Química de Córdoba, Argentina.Fil: Ferrayoli, Carlos. Ministerio de Ciencia y Tecnología de la Provincia de Córdoba. Departamento de Química, Argentina
Síntesis de derivados del ácido 4-fenilbutírico para el tratamiento de enfermedades poco frecuentes : medicamentos huérfanos
No full textTesis (Doctora en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2025Fil.: Suchetti, Laura. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Las enfermedades poco frecuentes (EPOF) constituyen un desafío sanitario global por su baja prevalencia, elevada complejidad diagnóstica, pronósticos graves y, en muchos casos, ausencia de tratamientos efectivos. Los medicamentos destinados a su manejo, denominados “medicamentos huérfanos”, presentan escaso interés comercial, alto costo y disponibilidad limitada. Entre ellos, el fenilbutirato de sodio (NaPB) y fenilbutirato de glicerol (GPB) son profármacos del ácido 4-fenilbutírico (4-PBA) empleados en el tratamiento de la hiperamonemia, patología incluida en el listado nacional de EPOF. En Argentina, el GPB no se produce localmente y su provisión depende de la importación a través del Régimen de Accesibilidad de Excepción a Medicamentos No Registrados (RAEM). En este contexto, la presente Tesis Doctoral se orienta en dos grandes ejes. Por un lado, aborda la síntesis y optimización de diferentes rutas de obtención de GPB, incluyendo tanto el método clásico con cloruro de tionilo como métodos alternativos basados en reactivos y condiciones compatibles con los principios de la Química Verde. Se estudian en detalle las condiciones de reacción, los rendimientos y la eficiencia de los procesos de purificación, así como la identificación y caracterización de impurezas asociadas a la síntesis. Asimismo, se desarrolla y valida un método de cromatografía líquida de alta resolución indicativo de estabilidad, apto para la valoración cuantitativa de GPB y para el control de sus impurezas de origen sintético. La validación incluye la evaluación de parámetros como especificidad, linealidad, exactitud, precisión, estabilidad de las soluciones, robustez y límites de detección, cumpliendo con los lineamientos internacionales. Finalmente, se realizan estudios de estabilidad a largo plazo y en condiciones aceleradas sobre tres lotes de producción de GPB, con el fin de establecer su comportamiento frente a distintos factores de degradación tales como temperatura y humedad. Por otro lado, aborda el diseño, síntesis y caracterización de nuevos derivados del 4-PBA obtenidos mediante esterificación con polioles derivados de azúcares. Estos compuestos se proponen como profármacos potenciales similares a GPB, buscando mejorar las propiedades fisicoquímicas y farmacocinéticas del principio activo. Se describen las metodologías de síntesis empleadas, el análisis de los rendimientos y purezas alcanzadas, así como la elucidación estructural detallada mediante técnicas de espectroscopia de resonancia magnética nuclear y de espectrometría de masas. Además, se discuten las implicancias de las modificaciones estructurales sobre la estabilidad química y el posible perfil de liberación del 4-PBA. En conjunto, los resultados obtenidos constituyen un aporte significativo al conocimiento de la síntesis, control de calidad y estabilidad del GPB, así como al desarrollo de nuevos derivados del 4-PBA con potencial interés farmacéutico. Este trabajo sienta bases sólidas para el escalado y eventual producción local de GPB.Rare diseases (RDs) represent a global health challenge due to their low prevalence, diagnostic complexity, severe prognoses, and, in many cases, the absence of effective treatments. The drugs used for their management, known as “orphan drugs,” are characterized by limited commercial interest, high cost, and restricted availability. Among them, sodium phenylbutyrate (NaPB) and glycerol phenylbutyrate (GPB) are prodrugs of 4-phenylbutyric acid (4-PBA), used in the treatment of hyperammonemia—a condition included in the national list of rare diseases. In Argentina, GPB is not produced locally, and its supply depends on importation through the Special Access Regime for Unregistered Medicines (RAEM). In this context, the present Doctoral Thesis is structured around two main axes. First, it addresses the synthesis and optimization of different routes for GPB production, including both the conventional method using thionyl chloride and alternative methods based on reagents and conditions aligned with the principles of Green Chemistry. Reaction conditions, yields, and purification efficiency were studied in detail, along with the identification and characterization of synthesis-related impurities. In addition, a stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated for the quantitative determination of GPB and for monitoring its synthetic impurities. Validation included the assessment of parameters such as specificity, linearity, accuracy, precision, solution stability, robustness, and detection limits, in compliance with international guidelines. Finally, long-term and accelerated stability studies were carried out on three production batches of GPB to evaluate its behaviour under various degradation factors such as temperature and humidity. The second axis focuses on the design, synthesis, and characterization of new 4-PBA derivatives obtained through esterification with sugar-derived polyols. These compounds are proposed as potential GPB-like prodrugs aimed at improving the physicochemical and pharmacokinetic properties of the active ingredient. The employed synthetic methodologies, achieved yields and purities, and detailed structural elucidation by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry are described. Furthermore, the implications of structural modifications on chemical stability and the potential release profile of 4-PBA are discussed. Overall, the results obtained represent a significant contribution to the knowledge of GPB synthesis, quality control, and stability, as well as to the development of new 4-PBA derivatives with potential pharmaceutical relevance. This work lays a solid foundation for the scaling up and potential local production of GPB, and for the exploration of new therapeutic alternatives for rare and other diseases.2027-11-30Fil.: Suchetti, Laura. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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