The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses

Territorio, fiscalidad y actividad militar en la formación de un espacio fronterizo. La consolidación de Tortosa como límite extremo del al-Andalus omeya

This work focuses on analysing the changes in the territorial control of Tortosa during the Umayyad period through three main lines of approach: the administrative organisation of its domains, the implementation of efficient tax policies and tribute collection mechanisms, and military activity regarding fortress construction and troop mobilisation. In this way, this text presents a critical analysis of written and archaeological sources in order to undertake a historical interpretation of the process under study within this territory.El objetivo principal de este trabajo es el de analizar los cambios en el control territorial andalusí de la circunscripción de Tortosa durante el período omeya mediante el estudio de tres ejes principales: la organización administrativa de sus dominios; la implementación de una fiscalidad eficiente con sus correspondientes mecanismos recaudatorios; y, finalmente, la actividad militar en la frontera a través de la construcción de fortificaciones y los contingentes allí movilizados. Para ello, se ha realizado un análisis crítico de las fuentes escritas y arqueológicas de las que se dispone para este territorio

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor

Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease

Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue-specific protein expression patterns. Global transcriptome analyses have suggested that >90% of human multiexon genes are alternatively spliced. Alterations in the splicing process cause missplicing events that lead to genetic diseases and pathologies, including various neurological disorders, cancers, and muscular dystrophies. In recent decades, research has helped to elucidate the mechanisms regulating alternative splicing and, in some cases, to reveal how dysregulation of these mechanisms leads to disease. The resulting knowledge has enabled the design of novel therapeutic strategies for correction of splicing-derived pathologies. In this review, we focus primarily on therapeutic approaches targeting splicing, and we highlight nanotechnology-based gene delivery applications that address the challenges and barriers facing nucleic acid-based therapeutics.Fil: Suñé Pou, Marc. Universidad de Barcelona; EspañaFil: Limeres, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Moreno Castro, Cristina. Institute of Parasitology and Biomedicine “López-Neyra"; EspañaFil: Hernández Munain, Cristina. Institute of Parasitology and Biomedicine “López-Neyra"; EspañaFil: Suñé Negre, Josep M.. Universidad de Barcelona; EspañaFil: Cuestas, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Suñé, Carlos. Institute of Parasitology and Biomedicine “López-Neyra"; Españ

Clinical evaluation of a new artificial saliva in spray form for patients with dry mouth

Objectives: To determine the efficacy of a new saliva substitute in spray form, for patients with dry mouth. Study design: Thirty-seven patients with dry mouth were selected (16 males and 21 females), with an age of over 60 years and meeting the following inclusion criteria: xerostomia and hyposialia confirmed by sialometry (resting whole saliva / stimulated whole saliva). A new artificial saliva in spray format was applied, with evaluation of the degree of improvement (VAS scale), frequency of application, time to improvement in minutes, duration in minutes, and assessment of organoleptic properties. Results: Twenty of the 37 patients showed almost immediate improvement after application. The mean number of applications/day was 3.89, with a mean duration of effect of 15.3 min. (65% > 15 min.). The flavor was rated as pleasant by 18 patients. Conclusions: Application of the spray is simple and effective, affording immediate relief, and with reasonable acceptance among patients with dry mouth

Aportaciones a la tecnología del vidrio para inyectables : dimensiones y fuerza de ruptura de las ampollas

Tesi de Llicenciatura per a la obtenció del Grau de Farmàcia. Facultat de Farmàcia. Universitat de Barcelona. Director: Josep Cemeli Pons, José María Suñé Arbussà. 1984

Aportación al estudio de las ampollas de fácil ruptura de uso farmacéutico: ensayo de fuerza de ruptura

[spa] Se realiza un amplio estudio experimental con el fin de mejorar el ensayo de control de calidad de la fácil ruptura de las ampollas de uso farmacéutico que presentan esta característica, aplicando una nueva metodología e instrumentación. Esta nueva técnica de ensayo, ya propuesta en la tesina de grado, se perfecciona estudiando las variables inherentes al método que puedan influir en la obtención de los valores de fuerza de ruptura, determinándose las condiciones óptimas de ensayo que lo hagan fácilmente reproducible y objetivo proponiéndose una normativa definitiva que lo estandariza. Con el fin de demostrar la mejora que comporta la metodología original que se propone, se comparan los resultados obtenidos con los que se hallan utilizando el método de Simoncini, que es el más empleado por la industria farmacéutica y los fabricantes de ampollas. Por otro lado, se profundiza en el estudio de aquellas variables inherentes a la ampolla de fácil ruptura que, en principio, pudieran influir sobre su correcta o incorrecta apertura, considerando sobre los distintos sistemas de fácil ruptura existentes en el mercado. Se utiliza para la realización de los ensayos un dinamómetro electrónico J.J. Lloyd Instruments al que se acoplan dos mordazas, una superior y otra inferior, de diseño propio (totalmente original) y fabricados en acero. Empleando ampollas procedentes de 6 fabricantes distintos se ensayan series de 100 ampollas por lote, realizándose las siguientes observaciones: fuerza de ruptura (N), tipo de rotura y estado final de la ampolla. Consta el trabajo de 7 grandes apartados experimentales, en cada uno de los cuales se realiza el estudio estadístico pertinente y correspondientes representaciones gráficas obtenidas en el registrador grafico que se dispone acoplado al dinamómetro electrónico que se emplea

Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease

Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue-specific protein expression patterns. Global transcriptome analyses have suggested that >90% of human multiexon genes are alternatively spliced. Alterations in the splicing process cause missplicing events that lead to genetic diseases and pathologies, including various neurological disorders, cancers, and muscular dystrophies. In recent decades, research has helped to elucidate the mechanisms regulating alternative splicing and, in some cases, to reveal how dysregulation of these mechanisms leads to disease. The resulting knowledge has enabled the design of novel therapeutic strategies for correction of splicing-derived pathologies. In this review, we focus primarily on therapeutic approaches targeting splicing, and we highlight nanotechnology-based gene delivery applications that address the challenges and barriers facing nucleic acid-based therapeutics

Gene Control during Transcription Elongation

Peer Reviewe

Targeting Splicing in the Treatment of Human Disease

The tightly regulated process of precursor messenger RNA (pre-mRNA) alternative splicing (AS) is a key mechanism in the regulation of gene expression. Defects in this regulatory process affect cellular functions and are the cause of many human diseases. Recent advances in our understanding of splicing regulation have led to the development of new tools for manipulating splicing for therapeutic purposes. Several tools, including antisense oligonucleotides and trans-splicing, have been developed to target and alter splicing to correct misregulated gene expression or to modulate transcript isoform levels. At present, deregulated AS is recognized as an important area for therapeutic intervention. Here, we summarize the major hallmarks of the splicing process, the clinical implications that arise from alterations in this process, and the current tools that can be used to deliver, target, and correct deficiencies of this key pre-mRNA processing event. Keywords: alternative splicing, precursor messenger RNA, therapy, genetic diseas