La calidad de los medicamentos fabricados industrialmente en España entre 1850 y 1950. Revisión de los requerimientos de calidad establecidos para los medicamentos en la legislación oficial durante este período

Objetivo: Estudiar la evolución de los requerimientos de calidad establecidos en los expedientes de solicitud de autorización de los medicamentos fabricados industrialmente desde 1850 a 1950 y su relación con la calidad de los mismos, teniendo en cuenta la influencia del contexto político-social. Material y métodos: Análisis de la legislación publicada en España referente al Registro Farmacéutico desde 1850 hasta 1950, comparando las referencias a la calidad de cada documento con las de la legislación inmediatamente anterior destacando lo que representa un avance. Consulta de revistas y documentos no publicados. Discusión de la evolución de la calidad de los medicamentos relacionándola con el contexto político-social del país. Resultados y conclusiones: Hasta 1855 no se podía hablar de medicamentos sino de remedios secretos. La Ley de 28 de Noviembre de 1855 estableció la obligación de declarar los remedios a la Autoridad Sanitaria. Posteriormente el Real Decreto de 1919 estableció el Registro Farmacéutico y la asignación del nº de registro. El Real Decreto de 1924 lo actualizaba sin avanzar en la calidad. Siguió un estancamiento tanto en normativa como en calidad, debido a la guerra civil y al bloqueo internacional. La Ley de Bases de 1944 anunciaba una reforma que aún tardó en producirse. En resumen período largo y cambiante con bastantes avances en organización y pocos en exigencias de calidad. Los expedientes de registro son un elemento de referencia fundamental para conocer la calidad de un medicamento en un momento determinado.Objectives: The aim is to study the evolution of quality requirements in the application file for approval of drug products and their relationship with the quality of industrially manufactured drugs between 1850 and 1950, taking into account the influence of political and social context. Materials and methods: Analysis of the legislation published in Spain referring to pharmaceutical registration from 1850 to 1950, comparing the quality benchmarks to highlight the improvement. Search of information in journals and unpublished documents. Discussion on quality progress related to the socio-political context of the country. Results and conclusions: Until 1855 drugs did not exist as such, there were only secret remedies. The Law of November 28, 1855 established the obligation to declare the remedies to the Health Authority. Since then there was an evolution until the Royal Decree of 1919 established the official register of medicines and assigned a registration number to each medicine. The Royal Decree of 1924 updated the 1919 Decree but no advance was done referring to quality. Then a period of stagnation followed in both the rules of registration and the quality due to the civil war and the international blockade. A Law Reform was announced in 1944 but it took a long time to be done. Summarizing: It was a long period, with advances in organization and little progress in quality requirements in the pharmaceutical registration. When quality requirements increased, drug quality also did. Application files for registration are an essential reference to know the quality at some time

Crude and refined oils from Elaeis guineensis: Facile characterization by FTIR and thermal analysis techniques

From an industrial perspective, fast characterization of raw materials provides an important tool for preventing manufacturing problems and contributes to assure the quality of the final products. In this work, several fast, cheap, and simple methods (Fourier transform infrared spectroscopy (FTIR) and various thermoanalytical techniques) were used for screening and characterization of crude and refined palm oils and other palm-derived products. The FTIR spectra allowed for ready distinction between mesocarp-derived products and those obtained from the kernel. The same applied to high-temperature differential scanning calorimetry (DSC) and differential thermal analysis (DTA) thermograms and the low-temperature DSC curves, in which the peak values and the presence or absence of certain peaks also permitted to differentiate among the various oils and fractions. Correspondences of mesocarp-derived oils with olein and kernel-derived oils with stearin were confirmed by both analytical methods and from the crystallization study. The relationship between the triglyceride composition and the FTIR and thermal profiles of the various palm-derived products has potential to be utilized as a facile quality control method in mill plants and laboratories

La calidad de los medicamentos fabricados industrialmente en España entre 1944 y 1992. Revisión de los requerimientos de calidad establecidos en la legislación oficial durante este período

Objetivo: Estudiar la evolución de los requerimientos de calidad para la solicitud de autorización de los medicamentos y los avances en la calidad de los mismos en el periodo comprendido entre 1944 y 1992. Como objetivo secundario evidenciar la influencia en los requerimientos de calidad de circunstancias excepcionales acaecidas en la propia sociedad o en los medicamentos. Material y Métodos: Análisis de la legislación publicada en España referente al registro farmacéutico desde 1944 hasta 1992, extrayendo y comparando las referencias de calidad a fin de destacar lo que representa un avance. Consulta de revistas especializadas y documentos no publicados relacionados con la industria farmacéutica. Discusión de los avances en calidad relacionándolos con el contexto político-social del país. Resultados y conclusiones: Los primeros años de este período siguieron la tónica del final del período anterior, años comprendidos entre 1850-1950, y que fue analizado en un artículo publicado anteriormente, es decir muy pocos avances en calidad. Únicamente cabe destacar, en 1954, el establecimiento de la visita de inspección al laboratorio previa a la autorización del medicamento. El Decreto 2464/1963 representó el primer gran avance en las exigencias de calidad para el registro desde 1919. Entre 1963 y 1973 no se produjo ningún cambio significativo en el contenido de los expedientes de registro. Finalmente el Decreto 1416/1973 introdujo cambios importantes en la tramitación de los expedientes que pasaron a tener dos fases: la primera consistía en la revisión de la documentación y concluía con una autorización (denominada Conforme Sanitario) para elaborar un primer lote del medicamento, la segunda fase implicaba el análisis de dicho lote por el Centro Nacional de Farmacobiología y comportaba la autorización o denegación del registro solicitado. La adaptación de los Laboratorios a esta nueva normativa especialmente en lo que se refería al contenido técnico y presentación de los expedientes no fue fácil puesto que en dichos expedientes se evidenciaron deficiencias durante bastante tiempo. Durante los años finales de este período, en puertas de la entrada de España en la Comunidad Europea, la legislación intentaba recoger o al menos no contradecir la normativa europea vigente. La publicación de la Ley 25/90 del medicamento introdujo, desde el punto de vista general, el Concepto de Garantía para asegurar la calidad, eficacia y seguridad e incluyó la exigencia de los avales de un experto para las informaciones contenidas en los expedientes, iniciándose así un cambio en las responsabilidades: el experto toma sobre sí la responsabilidad de la revisión de la documentación. En resumen, periodo con muchos cambios en la calidad en el contexto mundial. En la legislación española, dos importantes Decretos en 1963 y 1973. En los años finales de este periodo la legislación española se empezó a preparar para la transposición de la normativa europea referente a los medicamentos debía que tener lugar en 1992.Aim: The aim is to study the evolution of quality requirements in the application file for approval of drug products and their relationship with the quality of industrially manufactured drugs between 1944 and 1992. As a secondary objective, demonstrate the influence on the quality requirements of exceptional circumstances that occurred in the society or on drugs Materials and Methods: The early years of this period continued the trend of the previous period with very little improvement in quality. Only in 1954 the establishment of the laboratory inspection prior to approval of the drug was an important change. Decreto 2464/1963, represented the first important advance in the quality requirements for registration since 1919. Between 1963 and 1973 there was no significant change in the content of the registration dossiers. Finally, Decreto 1416/1973 introduced new changes in the application process that happened to have two phases: first one, the review of the written information which concluded with an Authorisation (called Conforme Sanitario) to manufacture a first batch of the product. The second phase was the analysis of this batch. For the Laboratories was not easy to adapt to this new procedure and the registration documents remained deficient for a long time. During the final years of this period, just before the entrance of Spain in the European Community, all the new legislation attempted to collect or at least not contradict existing European legislation. The publication of Law 25/90 introduced, the concept of Quality Assurance to ensure the quality, efficiency and safety of drugs, and ordered the inclusion of an expert review for the information contained in the files. The responsibilities began to change: the expert takes upon himself the responsibility of reviewing the documentation. Summarizing: Period with many quality changes in the global context. Referring Spanish law, they were two important Decretos in 1963 and 1973. In the final years of this period the Spanish regulation began to prepare for implementation of the European legislation regarding drugs that should take place in 1992

Molecular and morphological characterization of the grapevine cultivars “Italia” in the Ica and Cañete valleys (Peru)

The denomination of “Uva de Italia” or “Italia” is commonly used by growers to refer to a group of varieties used from the colonial times to making a brandy of Pisco with muscat aroma. Previous work have demonstrated that Uva de Italia corresponds in fact to the variety Muscat of Alexandria, a widely spread variety around the world and in South America. However, the distinction between “Italia Dorada” and “Italia Rosada” is usually made, in allusion to the color variations observed in the berries. Our aim was to characterize 5 samples collected in vineyards from the valleys of Ica and Cañete. The genotypes were identified using 13 molecular markers of nuclear simple sequence repeat, and 23 morphological descriptors according to OIV. Our results showed that four genotypes were identified as Muscat of Alexandria while the other corresponded to variety well-known in Argentina as Moscatel Rosado or Uva Pastilla in Chile respectively. Moscatel Rosado showed functionally female flowers, with variable berries size and color in the range from greenish yellow through pink. This is the first identification of Moscatel Rosado as a variety present in the Peruvian vineyards and would allow its use in the pisco industry with distinctive aromatic characteristics. Keywords: Italia, Muscat of Alexandria, Moscatel Rosado, variety identification, parentage analysis, microsatellites, Pisco

Vibrational and thermal studies of essential oils derived from Cistus ladanifer and Erica arborea shrubs

Producción CientíficaEssential oils from the two most representative shrub species from the Iberian Peninsula (namely Cistus ladanifer L. and Erica arborea L.) have been characterized by Fourier transform infrared spectroscopy (FTIR) and thermoanalytical techniques (TG/DTG and DSC). Vibrational spectra have been compared with those of components of the plants, and with those of oils, gums and resins from other species. The different content in terpenoids of C. ladanifer oil (mainly mono- and sesquiterpenoids) and E. arborea oil (mainly triterpenoids) is reflected in the ATR-FTIR by the position of the bands at around 2873 cm−1, 1730 cm−1 and 1678 cm−1. As regards their thermal behavior, C. ladanifer-derived oil evinced higher thermal stability than that of obtained from E. arborea: the pyrolysis of the former was sensitized at 210°C, whereas for the later it occurred at 143°C. These temperatures are high enough to state that thermolabile constituents such as terpenoids are conserved in the hydrodistillation and that this extraction process ensures the recovery of the main constituents of both essential oils.Programa LIFE+ de la Unión Europea (Proyecto LIFE11 ENV/ ES/000535)Fundação para a Ciência e a Tecnologia (FCT) (Proyecto UID/QUI/UI0313/2013

Prediction of huge X-ray Faraday rotation at the Gd N_4,5 threshold

X-ray absorption spectra in a wide energy range around the 4d-4f excitation threshold of Gd were recorded by total electron yield from in-plane magnetized Gd metal films. Matching the experimental spectra to tabulated absorption data reveals unprecedented short light absorption lengths down to 3 nm. The associated real parts of the refractive index for circularly polarized light propagating parallel or antiparallel to the Gd magnetization, determined through the Kramers-Kronig transformation, correspond to a magneto-optical Faraday rotation of 0.7 degrees per atomic layer. This finding shall allow the study of magnetic structure and magnetization dynamics of lanthanide elements in nanosize systems and dilute alloys.Comment: 4 pages, 2 figures, final version resubmitted to Phys. Rev. B, Brief Reports. Minor change

Hybrid materials based on polyethylene and MCM-41 microparticles functionalized with silanes: catalytic aspects of in situ polymerization, crystalline features and mechanical properties

New nanocomposites based on polyethylene have been prepared by in situ polymerization of ethylene in presence of mesoporous MCM-41. The polymerization reactions were performed using a zirconocene catalyst either under homogenous conditions or supported onto mesoporous MCM-41 particles, which are synthesized and decorated post-synthesis with two silanes before polymerization in order to promote an enhanced interfacial adhesion. The existence of polyethylene chains able to crystallize within the mesoporous channels in the resulting nanocomposites is figured out from the small endothermic process, located at around 80 C, on heating calorimetric experiments, in addition to the main melting endotherm. These results indicate that polyethylene macrochains can grow up during polymerization either outside or inside the MCM-41 channels, these keeping their regular hexagonal arrangements. Mechanical response is observed to be dependent on the content in mesoporous MCM-41 and on the crystalline features of polyethylene. Accordingly, stiffness increases and deformability decreases in the nanocomposites as much as MCM-41 content is enlarged and polyethylene amount within channels is raised. Ultimate mechanical performance improves with MCM-41 incorporation without varying the final processing temperature

Brain aging and Parkinson's disease: new therapeutic approaches using drugs delivery systems

ABSTRACT The etiology and pathogenesis of Parkinson’s disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alphasynuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed

Asteroseismology of red giants & galactic archaeology

Red-giant stars are low- to intermediate-mass ($M \lesssim 10$~M$_{\odot}$) stars that have exhausted hydrogen in the core. These extended, cool and hence red stars are key targets for stellar evolution studies as well as galactic studies for several reasons: a) many stars go through a red-giant phase; b) red giants are intrinsically bright; c) large stellar internal structure changes as well as changes in surface chemical abundances take place over relatively short time; d) red-giant stars exhibit global intrinsic oscillations. Due to their large number and intrinsic brightness it is possible to observe many of these stars up to large distances. Furthermore, the global intrinsic oscillations provide a means to discern red-giant stars in the pre-helium core burning from the ones in the helium core burning phase and provide an estimate of stellar ages, a key ingredient for galactic studies. In this lecture I will first discuss some physical phenomena that play a role in red-giant stars and several phases of red-giant evolution. Then, I will provide some details about asteroseismology -- the study of the internal structure of stars through their intrinsic oscillations -- of red-giant stars. I will conclude by discussing galactic archaeology -- the study of the formation and evolution of the Milky Way by reconstructing its past from its current constituents -- and the role red-giant stars can play in that.Comment: Lecture presented at the IVth Azores International Advanced School in Space Sciences on "Asteroseismology and Exoplanets: Listening to the Stars and Searching for New Worlds" (arXiv:1709.00645), which took place in Horta, Azores Islands, Portugal in July 201

New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification

Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of 18F-DOPA and 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, 18F-DOPA and 11C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of 11C-DTBZ PET. A symmetric reduction in striatal 11C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet