Cost of drugs manufactured by the University Hospital - role of the Central Pharmacy

The hospital pharmacy in large and advanced institutions has evolved from a simple storage and distribution unit into a highly specialized manipulation and dispensation center, responsible for the handling of hundreds of clinical requests, many of them unique and not obtainable from commercial companies. It was therefore quite natural that in many environments, a manufacturing service was gradually established, to cater to both conventional and extraordinary demands of the medical staff. That was the case of Hospital das Clinicas, where multiple categories of drugs are routinely produced inside the pharmacy. However, cost-containment imperatives dictate that such activities be reassessed in the light of their efficiency and essentiality. METHODS: In a prospective study, the output of the Manufacturing Service of the Central Pharmacy during a 12-month period was documented and classified into three types. Group I comprised drugs similar to commercially distributed products, Group II included exclusive formulations for routine consumption, and Group III dealt with special demands related to clinical investigations. RESULTS: Findings for the three categories indicated that these groups represented 34.4%, 45.3%, and 20.3% of total manufacture orders, respectively. Costs of production were assessed and compared with market prices for Group 1 preparations, indicating savings of 63.5%. When applied to the other groups, for which direct equivalent in market value did not exist, these results would suggest total yearly savings of over 5 100 000 US dollars. Even considering that these calculations leave out many components of cost, notably those concerning marketing and distribution, it might still be concluded that at least part of the savings achieved were real. CONCLUSIONS: The observed savings, allied with the convenience and reliability with which the Central Pharmacy performed its obligations, support the contention that internal manufacture of pharmaceutical formulations was a cost-effective alternative in the described setting.

Relatório de estágio no departamento central de investigação e acção penal

The means of obtaining evidence, the amount of evidence obtained, the number of defendants related to each criminal case and the gravity of the crimes for which the magistrates of the Department are holders of penal action, define its real importance to the Rule of Law. I have deeply studied the subject of the institution of hierarchical intervention required by the assistant and the application of an opening statement by the defendant, starting from a hypothetical case, provided when the query of an investigation with the subject of the crime of active corruption, where this institution was called as a reaction to the archiving dispatch delivered by the Public Ministry. I have study about the implementation of the institution of provisional suspension of the process, specifically in the scope of fiscal criminality, analyzing the effective satisfaction of the purposes of the sentences in two slopes: general prevention and special prevention. I went for my first time to a Central Court of Criminal Instruction, where I attended the measures of inquiry and instructive debate of a process that culminated with the prosecution and pronunciation of the defendants. In addition to this criminal experience, I have deepened and consolidated the academic knowledge with the study of various criminal cases from various fields in the scope of criminality investigated by the Department. I could therefore check the basis of procedural delays, regarding to our legal system, especially in this type of crime, raising issues that I analyzed and discussed, always in a critical and academic way. I had the opportunity to attend and witness a seminar in the Lisbon Directorate of Finance as well of entering the Centre for Judicial Studies to attend a conference on the International Anti-Corruption Day. Focus on the investigatory importance of the international judicial cooperation, through the various organs, with special interest to EUROJUST. I comprehended the organization and functioning of these communitarian organs and means of communication of procedural acts, in particular, the rogatory letters and european arrest warrants. This involvement is motivated by the moratorium factor of the investigations where rogatory letters are necessary for the acquisition of evidence or information relevant to the good continuation of the process. For this reason the judicial cooperation through the relevant communitarian organs, translates a streamlined response between the competent judicial authorities of the Member States, through the National Member that integrates EUROJUST. This report aims to highlight some of the difficulties and procedural issues that Public Prosecutors of DCIAP and criminal police bodies that assist them, face in combating violent and organized crime, of national and transnational nature, of particular complexity, according to the specifics of criminal types.

An experimental model for the transplantation of fetal central nervous system cells to the injured spinal cord in rats

INTRODUCTION: Traumatic spinal cord injury is one of the most disabling conditions occurring in man and thus stimulates a strong interest in its histopathological, biochemical, and functional changes, primarily as we search for preventive and therapeutic methods. PURPOSE: To develop an experimental model for transplantation of cells from the fetal rat central nervous system to the site of an injured spinal cord of an adult rat in which the transplanted cells survive and become integrated. This experimental model will facilitate investigations of factors that promote regeneration and functional recovery after spinal cord trauma. MATERIAL AND METHODS: Fifteen adult Wistar rats underwent laminectomy, and an spinal cord lesion was made with microdissection. Fetal spinal cord tissue was then transplanted to the site of the injury. The rats were monitored over a 48-hour period, and then their vertebral column was completely removed for histological analysis. RESULTS: In 60% of transplanted rats, the fetal tissue at the injured site remained viable in the site of the lesion.

Local Rainfall Variability - A Potential Bias for Bioecological Studies in the Central Amazon

Rainfall data registered betwe en 1910 and 1979 at Manaus confirm the existence of a dry season between June and November (monthly rainfall: 42-162mm) and a rainy season from December until May (monthly rainfall: 211-300mm). Annual precipitation amounted to 2105mm with about 75% of the rainfall recorded during the rainy season. Rainfall data collected over 12 months at eigth stations in the vicinity of and at Manaus are compared. Annual precipitation was lower in Inundation Regions (1150-2150mm) compared with Dryland Regions (2400-2550mm). Considerable differences are found in rainfall patterns (intensity, frequency and time of rainfall). This is also truefor neighbouring stations, even if data of a 11-year record period are compared. Thus, it is highly recommended that preciptation data for bioecological studies be collected at the study site.

Estudos Silviculturais de uma População Natural de COPAIFERA MULTIJUGA Hayne - Leguminosae, na Amazônia Central. 3. Distribuição Espacial da Regeneração Natural Pré-Existente

Mostra-se a distribuição espacial de. plântulas de Copaifera multijuga, Hayne de 12árvores matrizes. 0 potencial de regeneração em área não perturbada é variável em decorrência da maior ou menor produção de sementes pelas matrizes, da competição entre plântulas da espécie e destas com plântulas deoutras espécies, além da provável predaçãopor animais e da luta para sobreviver a baixos níveis de radiação solar. a distribuição das freqüências das plântulus sugere uma forma de J invertido. Nos dois inventários feitos, a altura das plântulas variou de 10cm até um máximo de 50cm, sendo a altura média para as 12 matrizes de. 20,66cm e 15,54cm no1° e 2° inventários, respectivavente. a diferença na variância das alturas das plântulas é significativa, na faixa de5%. As freqüências relativas esperadas, segundo a equação de Poisson, mostrou que a distribuição da regeneração de todas as matrizes é do tipo agregado. 0 número de plântulas /árvore matriz pode ser silviculturalmente útil para fins de plantios, desde quesejam feitos estudos de adaptabilidade das plântulas às condições deviveiro.

Os peixes de um lago de várzea da Amazônia Central (Lago Janauacá, Rio Solimões) e suas relações com os crustáceos ectoparasitas (Branchiura: Argulidae)

Durante um período de treze meses, de março de 1979 a março de 1980, excursões semanais foram realizadas ao Janauacá, um complexo de, l.agos de várzea da Amazônia Central. Miltrezentos e trinta e cinco peixesde cinco ordens, dezenove famílias e. oitenta espécies foram examinados, visando a determinar os índices naturais de infestação por crustáceos da subclasse Branchiura. Dos peixes examinados 11% estavam parasitados e apresentaram uma média de cinco crustáceos por peixe. Os maiores índices de infestação ocorreram nos Siluroides, 29% de prevalência e 18,5 de intensidade de infestação, seguidos pelos Characoides com 8,4% e 2,5. Os Perciformes apresentaram o terceiro maior índi.ce, 7,4% de. prevalência e 2,0 de intensidade de infestação. Os menores índices ocorreram nos Osteoglossiformes, 3,0% e 5,0 e nos Clupeiformes com 4,0% e 1,0. Durante o período de coletas, dezoito espécies de peixes não ocorreram parasitadas por branquiuras. Catorze espécies de branquiuros foram coletados no lago Janauacá. Alguns aspectos taxionómicos , biogeográficos e econômicos dos peixes são abordados

Vocalizations of primary forest frog species in the Central Amazon.

The calls of 18 species of Amazonian forest frogs were recorded in 3 localities: the Tapajos National Park near Itaituba, the Reserva Ducke near Manaus, and the INPA-WWF reserves near Manaus. Structural and time parameters and sonographs of these calls including previously undescribed vocalization by 10 species are presented. Unlike open habitat species, several forest frong species characteriscally demonstrated one on more of the following temporal parameters: very low call rates, sporadic intervals, infrequent nights of calling and synchronized chorusing. It is hypothesized that predation has influenced the evolution of vocal behaviour in Amazonian forest frogs.

Correlação entre a capacidade de troca de cátions e outras propriedades de três solos da Amazônia Central

Foi determinada a capacidade de troca de cations a pH natural do solo e a pH 7,0 ao longo do perfil de três solos da Amazônia Central e correlaeionou-se os valores de CTC encontrados com outras características intrínsecas de cada solo, tais como: matéria orgânica, superfície especifica teor e mlneralogia da fração argila, as quais causam varia cão na CTC do solo. As diferenças entre os valores de CTC obtidos foram decorrentes principalmente do teor de matéria orgânica e da mlneralogla da fração argila. A matéria orgânica do solo apresentou-se altamente correlacionada com a CTC determinada a pH 7,0 dos solos Latossolos Amarelo (r - 0,998) e Podzolico l/ermelho Amarelo (r = 0,974), principalmente pana os horizontes de superfície, enquanto que para o solo Glei Pouco Húmico foram encontradas correlações significativas apenas ao nível de 5%. Para a CTC à pH natural do solo, altas correlações também foram obtidas somente para Latossolo (r= 0,980) e Podzoílco (r = 0,984). A correlação entre a superfície específica e a CTC do solo apresentou-se altamente significativa para o Latossolo (r = 0,957) e Glei Pouco Húmico (r = 0,952), enquanto que para o Podzoílco (r + 0,873), a correlação foi significativa apenas ao nível de 5%. Foi observado ainda que a classe textural, o teor de matéria orgânica e principalmente a composição mlneralóglca conferiram maiores valores ae super fície especifica para o solo Glel Pouco Húmico.

Efeito da aplicação de calcário e micronutrientes em latossolo amarelo da Amazônia Central

O efeito de diferentes níveis de colagem na presença de micronutrientes, foram testados na cultuha da soja, em Latossolo Amarelo da Amazônia Central, sob três áreas com diferentes maneiras de preparo do solo: desmatamento seguido da queima de floresta primária; desmatamento seguido da retirada da floresta primária com aso de maquinas e desmatamento seguido da queima de vegetação de capoeira. As produções obtidas com as doses 1, 3 c 5 ton/ka, na ausência de micronutrientes, não diferiram estatísticamente da testemunha (0 ton/ha). No entanto, com a aplicação de 2 ton/calcário mais micronutrientes, o aumento de produção foi bastante pronunciado. 0s menores rendimentos foram obtidos no solo preparo com o uso de máquinas. A disponibilidade de nutrientes em Latossolo Amarelo, assim como o preparo de solo é discutido.

Aspectos fenológicos e ecológicos do "Araça-Boi" (Eugenia stipitata MCVAUGH) na Amazônia Central. I. Plantas juvenis

O "araça-boi" (Eugenia stipitata) é uma fruteira arbustiva nativa da Amazônia que está sendo introduzida ma agricultura moderna. Estudou-se sua fenologia na Amazônia Central em latossolo amarelo, álico, textura média, durante os primeiros 15 meses de produção. Quando juvenlí, floresce continuamente durante o ano, com quatro períodos de alta produção. Como muitas fruteiras, produz mais flores que frutos (somente 15% das flores produzem frutos que chegam à maturação). A taxa de autopolinização natural é reduzida, sugerindo que a espécie é alógama. Os polinizadores principais são as abelhas. O tempo entre floração e maturação dos frutos e de aproximadamente 34 dias.

Estudos silviculturais de uma população natural de Copaifera multijuga Hayne - Leguminosae, na Amazônia Central. IV. Interpretação de dados fenológicos em relação a elementos climáticos

O autor apresenta informações fenológicas mensais de 82 matrizes de Copaiba (Copaifera multljuga Hayne), obtidas na Reserva Florestal Adolfo Ducke no período de fevereiro de 1979 a dezembro de 1985. São mostradas as percentagens de ocorrência das fases de floração, frutificação e mudança foliar e uma análise de regressão múltipla das fenofases com sete variáveis do clima (temperatura máxima, temperatura minima e temperatura média, em C°; umidade relativa em %; precipitação total em milímetros; insolação total em horas e evaporação líquida total em milímetros. A plena floração ocorreu na estação de chuvas e a frutificação (frutos maduros) apresentou picos máximos no fim da estação chuvosa e inicio da estação seca, comportamento que. difere da maioria das espécies arbóreas tropicais. A espécie portou-se como perenifólia e a fase de folhas novas antecedeu a da floração.

Primate populations in continuous forest and forest fragments in Central Amazonia

Population densities of six primate species (Saguinus midas, Pithecia pithecia, Cebus apella, Chiropotes satanas, Alouatta seniculus and Ateles paniscus) were estimated in continuous forest and in isolated reserves (one of 100 ha and four of 10 ha). Saguinusdensities in the continuous forest were found to be low, probably due to the lack of edge habitat and second growth favoured by them; Pithecia, Cebus and Ateles populations are also low, possibly because of more widely distributed and/or less abundant food sources than is true for other Amazonian regions, although hunting in the past, particularly of Ateles may also be a contributing factor; and Chiropotes and Alouatta densities were found to be similar to those observed in other areas of Amazonas forests. Ateles and Chiropotes, which occupy ranges on the order of three km2 were excluded from the 100-ka reserve at the time of its isolation. Unfortunately populations were not known prior to isolation of this reserve but during isolation there remained four groups of Saguinus, two Pitheciagroups, one Cebus groups and five Alouatta groups. One Saguinus group disappeared two months later, and one year post-isolation the Cebus group also left the reserve. Single Alouatta groups survive in the isolated 10-ha reserves. Saguinus, present in the four 10-ha reserves following isolation, have disappeared from two of them. One 10-ha reserve retains a group of Pithecia.

Distribution of Atta (Hymenoptera - Formicidae) in "terra-firme" rain forest of Central Amazonia: density, species composition and preliminary results on effects of forest fragmentation

One hundred and fourteen hectares of a "terra-fiirme" rain forest 70 km north of Manaus, Amazonas, Brazil, were surveyed for leaf-cutting ant colonies (Atta spp). One half of this area was in isolated forest fragments (surrounded by pastures or second growth) of two sizes: 1 and 10 ha. The other half was in non-isolated fragments (connected to a large parch of forest) of the same sizes. Only two species occured in this forest: Atta sexdens sexdens L. and A. cepfhalotes L. The first was the most abundant species with a mean density of 0.35 colonies per ha. The mean density of A. cephalotes colonies was 0.03 per ha. The density of colonies was not significantly different between the isolated fragments and the continuous forest. Furthermore, the species composition did not change with isolation. However, pre-isolation data and long term monitoring are necessary to conclude that the isolation of a forest fragment has no effect upon Atta colonies. The non-uniform spatial distribution of Atta colonics within the "terra-firme" forest must be taken into account when selecting conservation areas in the Amazon, in order to preserve this important group of ants together with their native habitat.

Development of human central nervous system 3D in vitro models for preclinical research

Neurological disorders are a major concern in modern societies, with increasing prevalence mainly related with the higher life expectancy. Most of the current available therapeutic options can only control and ameliorate the patients’ symptoms, often be-coming refractory over time. Therapeutic breakthroughs and advances have been hampered by the lack of accurate central nervous system (CNS) models. The develop-ment of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of novel therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmentally, anatomically and physiologically) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity). The in vitro recapitulation of CNS phenotypic and functional features requires the implementation of advanced culture strategies that enable to mimic the in vivo struc-tural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. This thesis aimed at the development of novel human 3D in vitro CNS models by integrat-ing agitation-based culture systems and a wide array of characterization tools. Neural differentiation of hNSC as 3D neurospheres was explored in Chapter 2. Here, it was demonstrated that human midbrain-derived neural progenitor cells from fetal origin (hmNPC) can generate complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Chapter 3 focused on the development of cellular characterization assays for cell aggregates based on light-sheet fluorescence imaging systems, which resulted in increased spatial resolu-tion both for fixed samples or live imaging. The applicability of the developed human 3D cell model for preclinical research was explored in Chapter 4, evaluating the poten-tial of a viral vector candidate for gene therapy. The efficacy and safety of helper-dependent CAV-2 (hd-CAV-2) for gene delivery in human neurons was evaluated, demonstrating increased neuronal tropism, efficient transgene expression and minimal toxicity. The potential of human 3D in vitro CNS models to mimic brain functions was further addressed in Chapter 5. Exploring the use of 13C-labeled substrates and Nucle-ar Magnetic Resonance (NMR) spectroscopy tools, neural metabolic signatures were evaluated showing lineage-specific metabolic specialization and establishment of neu-ron-astrocytic shuttles upon differentiation. Chapter 6 focused on transferring the knowledge and strategies described in the previous chapters for the implementation of a scalable and robust process for the 3D differentiation of hNSC derived from human induced pluripotent stem cells (hiPSC). Here, software-controlled perfusion stirred-tank bioreactors were used as technological system to sustain cell aggregation and dif-ferentiation. The work developed in this thesis provides practical and versatile new in vitro ap-proaches to model the human brain. Furthermore, the culture strategies described herein can be further extended to other sources of neural phenotypes, including pa-tient-derived hiPSC. The combination of this 3D culture strategy with the implemented characterization methods represents a powerful complementary tool applicable in the drug discovery, toxicology and disease modeling.

INFLUÊNCIA DA DENSIDADE NA DUREZA JANKA EM OITO ESPÉCIES MADEIREIRAS DA AMAZÔNIA CENTRAL

O presente trabalho teve por objetivo estudar a relação da densidade básica com a resistência de madeiras tropicais, submetidas ao teste de dureza Janka nos extremos e faces nas condições verde e seca a 12% de conteúdo de umidade. Foram utilizadas 8 espécies florestais oriundas do Distrito Agropecuário da SUFRAMA, no Município de Manaus, AM. O experimento foi realizado no laboratório de Engenharia da Madeira do Departamento de Produtos Florestais do Instituto Nacional de Pesquisas da Amazônia - INPA, adotando-se os seguintes passos: a)realização dos ensaios de densidade básica e dureza Janka empregados pela norma COPANT; b)tratamento estatístico de regressão linear para avaliar o nível de influência da densidade na dureza da madeira. Os resultados obtidos revelam que a dureza da madeira expressa pela sua capacidade em oferecer maior ou menor resistência à penetração de uma semi-esfera, está estreitamente relacionada com a densidade.