Class of 2012 Abstract / Specific Aims: To evaluate the in vitro throat deposition and respirable mass of the QVAR® pressurized metered-dose inhaler (pMDI) alone or coupled to an accessory device, such as the AeroChamber Valved Holding ChamberTM or various nonconventional accessory devices. Methods: The performance of the AeroChamber and nonconventional accessory devices, including a toilet paper roll, paper towel roll, rolled paper, plastic bottle spacer, plastic bottle reverse-flow holding chamber, and nebulizer reservoir tubing, were compared to no accessory device. Throat deposition and respirable mass were evaluated using a United States Pharmacopeia (USP) inlet ("throat") coupled to instrumentation for particle size analysis. Each configuration was tested with three actuations and repeated in quadruplicate. The amount of drug deposition was quantified using high-performance liquid chromatography. The data were analyzed using multiple independent t-tests assuming unequal variances. An a priori α-threshold of 0.05 was used with a Bonferroni corrected α of 0.007. Main Results: Compared to the pMDI alone, all of the accessory devices had significantly lower throat deposition (p < 0.001) and significantly higher respirable fraction (p < 0.001). Differences in respirable mass were not significant for any accessory device (p ≥ 0.049), except the paper towel roll and the nebulizer reservoir tubing (p < 0.001). Conclusions: Under these testing circumstances, nonconventional accessory devices, such as the toilet paper roll, rolled paper, plastic bottle spacer, and plastic bottle reverse-flow holding chamber, effectively reduce throat deposition and maintain respirable mass compared to a QVAR pMDI alone. Therefore, they may be suitable alternatives to commercial spacers.

Recent years have seen the establishment of several radionuclides as medicinal products in particular in the setting of theranostics and PET. [177Lu]Lutetium Chloride or [64Cu]Copper Chloride have received marketing authorization as radionuclide precursor, [68Ga]Gallium Chloride has received regulatory approval in the form of different 68Ge/68Ga generators. This is a formal requirement by the EU directive 2001/83, even though for some of these radionuclide precursors no licensed kit is available that can be combined to obtain a final radiopharmaceuticals, as it is the case for Technetium-99m. In view of several highly promising, especially metallic radionuclides for theranostic applications in a wider sense, the strict regulatory environment poses the risk of slowing down development, in particular for radionuclide producers that want to provide innovative radionuclides for clinical research purposes, which is the basis for their further establishment. In this paper we address the regulatory framework for novel radionuclides within the EU, the current challenges in particular related to clinical translation and potential options to support translational development within Europe and worldwide.

Le but de cette thèse est d’étudier comment, suite à la conquête de l’Amérique, les Européens se sont approprié des plantes médicinales d’origine mexicaine, caribéenne, andine, ou amazonienne. L’usage fréquent que les praticiens européens du XVIIIe siècle font de substances telles que le quinquina, l'ipécacuanha, le bois de gaïac ou encore le chocolat, révèle l’ampleur du phénomène, mais en masque la complexité. L’emploi d’un remède originaire d’Amérique en Europe implique en effet de nombreux processus. Le prélèvement et la mise en culture des végétaux, la transmission des savoirs indigènes et leur traduction par les allogènes, la commercialisation des drogues à travers l'Atlantique, les expériences réalisées sur les remèdes et les expéditions organisées en Amérique entre le XVIe et le XVIIIe siècle sont ainsi au cœur de cette recherche. Plus qu’un « apport » de l’Amérique à l’Europe, ce phénomène d’appropriation doit être appréhendé comme une modalité du fait colonial. Objet naturel, et en même temps savoir naturaliste et médical, la plante médicinale devient à la suite de la conquête de l’Amérique un enjeu politique. Elle suscite, en 1570, l’une des premières expéditions scientifiques de l’histoire, et inspire à la monarchie espagnole divers projets de monopole au milieu du XVIIIe siècle. De l’autre côté de l’Atlantique, elle est au cœur des conflits opposant l’« Indien » à l’Espagnol, lorsque le second interdit au premier d’utiliser des plantes abortives ou hallucinogènes, et lorsque le premier refuse de transmettre ses savoirs pharmacologiques au second. / The aim of this dissertation is to study how, in the aftermath of the Conquest of America, Europeans have appropriated medicinal plants from Mexican, Caribbean, Andean, or Amazonian origin. 18th century European practitioners frequently used substances such as Peruvian bark, ipecacuanha, gaiacum wood, or chocolate – which reveals the extent of the phenomena, yet masks its complexity. Using an American remedy in Europe indeed implied many processes. Crucial to this research are: the sampling and growing of plants; the transmission of indigenous knowledge and its translation by allogenous; the drug trade across the Atlantic; experiences carried out on remedies; and expeditions conducted in America between the 16th and the 18th centuries. More than a “contribution” of America to Europe, this phenomenon of appropriation must be understood as a modality of colonialism. As natural object, and at the same time as naturalistic and medical knowledge, medicinal plants took on a political stake after the Conquest of America. For instance, while in 1570 they had been the target of one of the first scientific expeditions in history, in the middle of the 18th century they also led the Spanish crown to undertake various monopolistic projects. On the other side of the Atlantic, it was at the heart of conflicts between the “Indian” and the Spaniard, when the latter forbade the former from using abortive or hallucinogenic plants, and when the former refused to transmit his pharmacological knowledge to the latter.

Submitted by Alexandre Sousa (alexandre.sousa@incqs.fiocruz.br) on 2015-04-10T14:28:00Z No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) / Approved for entry into archive by Alexandre Sousa (alexandre.sousa@incqs.fiocruz.br) on 2015-04-10T14:28:16Z (GMT) No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) / Approved for entry into archive by Alexandre Sousa (alexandre.sousa@incqs.fiocruz.br) on 2015-04-10T14:28:30Z (GMT) No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) / Made available in DSpace on 2015-04-10T14:28:30Z (GMT). No. of bitstreams: 1 Dissertacao_Nataly.PDF: 1054218 bytes, checksum: 3c023839345bc1fb63d761be1a4ad97d (MD5) Previous issue date: 2015 / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde / O sistema público de saúde no Brasil ainda não supre completamente as necessidades básicas de saúde da população. Considerando a necessidade de ampliar o atendimento à saúde da população e disponibilizar opções de medicina tradicional e práticas complementares, o governo brasileiro criou políticas e programas de saúde pública para incentivar o uso de plantas medicinais e medicamentos fitoterápicos. Assim, plantas medicinais reconhecidamente eficazes vêm sendo utilizadas no atendimento das necessidades básicas de saúde da população para a cura de uma variedade doenças e sintomas. Grande parte da população brasileira utiliza plantas medicinais, incluindo pacientes de faixas etárias e grupos de risco diversos, e que muitas vezes residem em locais em precárias condições de saneamento básico. Portanto, as plantas medicinais devem ser produtos de qualidade garantida, para que seu uso seja seguro e não possua riscos à saúde dos consumidores. Neste estudo, 15 amostras de plantas medicinais das espécies Baccharis trimera, Bauhinia forficata e Tabebuia avellanedae, de lotes diferentes e de 4 marcas, compradas na cidade do Rio de Janeiro, foram avaliadas quanto à qualidade microbiológica. A análise consistiu na quantificação dos microrganismos viáveis e na pesquisa de patógenos presentes nas amostras. A escolha dos limites de contaminação microbiana e dos patógenos a serem pesquisados foi realizada com base nas possíveis formas de preparo e uso de plantas medicinais. Foi realizada a quantificação de bactérias aeróbias, bactérias Gram-negativas bile tolerantes e bolores e leveduras viáveis, e a pesquisa dos outros patógenos Escherichia coli, espécies de Salmonella, espécies de Shigella, Pseudomonas aeruginosa, Staphylococcus aureus e Candida albicans. As plantas medicinais analisadas apresentavam contaminação bacteriana e fúngica variável, onde 93,3% possuía carga de contaminação microbiana acima dos limites de contaminação permitidos para bactérias aeróbias e bolores e leveduras. Adicionalmente, foi identificada a contaminação pelos patógenos S. aureus, P. aeruginosa, E. coli e bactérias Gram negativasbile tolerantes em 20%, 20%, 46,6% e 100% das amostras, respectivamente. Nenhuma das amostras de plantas medicinais apresentou qualidade sanitária suficiente para ser aprovada para o uso (100% de reprovação), constituindo um problema para a saúde pública, visto que um produto terapêutico contaminado é disponibilizado para uma população que já se encontra enferma, e demonstrando a necessidade de um melhor controle e regulamentação para estes produtos. / The public health system in Brazil does not yet supplies completely the population basic needs for health. Considering the necessity to expand the health care and to provide traditional and complementary medicine options, the brazilian government created public health politics and programs to encourage the use of medicinal plants and phytotherapic drugs. Thus, medicinal plants admittedly effective have been used for the care of the population’s basic needs, to heal a variety of diseases and symptoms. A large portion of the brazilian population use medicinal plants, including a diversity of age and risk group patients, whose many times resides in places with precarious sanitary conditions. Therefore, medicinal plants need to be assured quality products, to be used safely and not bring risks to the user’s health. In this study, 15 medicinal plants samples of Baccharis trimera, Bauhinia forficata and Tabebuia avellanedae species, all from different batches from 4 brands, bought in the city of Rio de Janeiro, were evaluated about their microbiological contamination. The assay consisted in the quantification of viable microorganisms and in the search of pathogens present in the samples. The choosing of the microbiologic contamination limits and the pathogens to be searched was made based on the possible preparation methods and use of medicinal plants. Quantification of viable aerobic bacteria, bile tolerant Gram negative bacteria and yeasts and molds, and search of the others pathogens Escherichia coli, Salmonella species, Shigella species, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans were executed. The medicinal plants samples analyzed had variable bacterial and fungal contamination, where 93,3% had microbial contamination load above the allowed contamination limits for aerobical bacteria and yeasts and molds. Additionally, contamination by S. aureus, P. aeruginosa, E. coli, and bile tolerant Gram negative bacteria were identified in 20%, 20%, 46,6% and 100% of samples, respectively. No samples of medicinal plants had enough sanitary quality to be approved to use (100% disapproval), constituting a public health problem, since a highly contaminated therapeutic product is made available to a population who already is diseased, showing the need of better control and regulation to these products.

Cette étude traite des savoirs et pratiques naturalistes relatifs à la flore aromatique et médicinale de la Corse et de leur mise en patrimoine. La pharmacopée traditionnelle et les croyances qui y sont associées sont étudiées dans un but de conservation et de valorisation puis mises en regard avec les pratiques actuelles d’utilisation de la flore (production d’huiles essentielles et de produits dérivés) afin d’étudier le processus de patrimonialisation des savoirs. Ce travail vise à contribuer à la conservation et à la valorisation d’un patrimoine associant le biologique et le culturel ainsi qu’à une meilleure compréhension de la relation de la société corse au végétal au cours du temps. Il s’inscrit également de manière plus générale, dans une perspective d’étude de l’espace insulaire comme lieu de compréhension de la conservation de la diversité culturelle et biologique. / This study deals with naturalist knowledge and practical experience about aromatic and medicinal flora from Corsica and their entering the heritage. Traditional pharmacopeia and the beliefs which are connected to it, are studied with the intention of conservation and promotion. Then they are compared with the present use of flora/the plants (production of essential oils and by-products) in order to examine the heritage recognition of that knowledge. That work is aimed at contributing to the conservation and promotion of a legacy combining both the organic and cultural aspects as well as a better understanding of the interest of the Corsican society in the knowledge of plants in the course of time. More generally it also follows a prospect to study how Corsica is outstanding to understand the conservation of cultural and organic diversity.

La médecine et la pharmacopée traditionnelles ouest-africaine constituent encore aujourd'hui, l'unique moyen de prise en charge des maladies pour des milliers de personnes vivant en zone rurale et même en zone urbaine. Cette réalité est souvent présentée comme découlant uniquement de la faiblesse du système allopathique de santé, cependant, elle peut être le fruit d'un choix socioculturel. En effet, les conceptions traditionnelles des maladies, c’est-à-dire la distinction entre maladies naturelles et maladies provoquées influencent encore le choix thérapeutique dans les communautés africaines surtout en zone rurale. Pendant longtemps, ce retour à la médecine et à la pharmacopée traditionnelle s'est fait sans la mise en place des mesures d'encadrement et d'accompagnement nécessaires. Ce qui engendre d’énormes risques sanitaires. De plus, la multiplication des bio-prospections sans contrôle des États a conduit à une forte croissance des appropriations illicites des savoirs tradimédicaux. Cet état des faits a fait émerger au sein des institutions internationales compétentes de nouvelles questions : celles des droits des communautés locales et autochtones sur leurs ressources et leurs savoirs tradimédicaux associés, et la nécessité de la construction d'un système équitable d'exploitation des ressources et des savoirs médicaux traditionnels à des fins de recherches et de développement. Les États burkinabè et ghanéen ont, pour pallier ces difficultés, adopté des législations encadrant les pratiques traditionnelles de soins ainsi que la production et la mise sur leurs marchés nationaux de médicaments traditionnels et néo traditionnels / Traditional medicine and pharmacopeia are still nowadays for thousands of people in West Africa, the unique healthcare solution. If this fact is often considered as arising solely from the weakness of the allopathic health system, it could also be a result of socio-cultural choices. Indeed, people especially in rural areas are strongly influenced by traditional vision and beliefs about diseases’ origins, which could have natural or induced causes in this traditional conception. For a long time, this resort to traditional medicine was done without the supervision and support of the appropriate measures and regulations. This has generated high public healthcare risks. Moreover, the multiplication of bioprospection’s without states control has led to a sharp increase in illicit appropriation of traditional medicine knowledge for the purposes of pharmaceutical innovation. This has created new issues in the South, especially about local populations’ intellectual property on their traditional knowledge. Highlighting these facts has raised new concerns within the competent international and regional institutions: the need of protection for local and indigenous communities’ rights over their genetic resources and associated tradimedical knowledge, and the need of building a fair system of exploitation of resources and medical indigenous knowledge for purposes of research and development. The Burkinabe and Ghanaian states have, in order to overcome these issues, adopted legislations to regulate traditional care practices as well as the production and placement on their national markets of traditional and neo-traditional medicines