Epidemiology of Cytochrome P450-mediated Drug-Drug Interactions

Drug-drug interactions (DDIs) comprise an important cause of adverse drug reactions leading to excess hospitalizations. Drug metabolism is catalyzed by 75% by cytochrome P450 (CYP) enzymes and thus they are often involved in pharmacokinetic DDIs. In general, DDIs are studied in randomized controlled clinical trials in selected study populations. The overall aim of the present studies was to perform observational pharmacoepidemiological surveys on CYP-mediated DDIs in diseases important at the population level. The prevalence of co-administrations of four prodrugs (losartan, codeine, tramadol, and clopidogrel), three sulphonylureas (glibenclamide, glimepiride, and glipizide), or two statins (lovastatin and simvastatin) with well established agents altering CYP activity, as well as of statins with fibrates, was studied in Finland utilizing data from a university hospital medication database (inpatients) and the National Prescription Register of the Social Insurance Institution of Finland, Kela (outpatients). Clinical consequences of potential DDIs were estimated by reviewing laboratory data, and information from hospital care and cause-of-death registers. Concomitant use of study substrates with interacting medication was detected in up to one fifth of patients in both hospital and community settings. Potential CYP3A4 interactions in statin users did not manifest in clear adverse laboratory values but pharmacodynamic DDIs between statins and fibrates predisposed patients to muscular toxicity. Sulphonylurea DDIs with CYP2C9 inhibitors increased the risk of hypoglycaemia. CYP3A4 inhibitor use with clopidogrel was not associated with significant changes in mortality but non-fatal thrombosis and haemorrhage complications were seen less often in this group. Concomitant administration of atorvastatin with clopidogrel moderately attenuated the antithrombotic effect by clopidogrel. The overall mortality was increased in CYP3A4 inducer and clopidogrel co-users. Atorvastatin used concomitantly with prodrug clopidogrel seems to be beneficial in terms of total and LDL cholesterol concentrations, and overall mortality compared with clopidogrel use without interacting medication. In conclusion, CYP-mediated DDIs are a common and often unrecognized consequence of irrational drug prescribing.

Flow injection visible diffuse reflectance quantitative analysis of total sulfur in biodiesel, in plant leaves and in natural waters

Flow injection (FI) methodology, using diffuse reflectance in the visible region of the spectrum, for the analysis of total sulfur in the form of sulfate, precipitated in the form of barium sulfate, is presented. The method was applied to biodiesel, to plant leaves and to natural waters analysis. The analytical signal (S) correlates linearly with sulfate concentration (C) between 20 and 120 ppm, through the equation S=-1.138+0.0934 C (r = 0.9993). The experimentally observed limit of detection is about 10 ppm. The mean R.S.D. is about 3.0 %. Real samples containing sulfate were analyzed and the results obtained by the FI and by the reference batch turbidimetric method using the statistical Student's t-test and F-test were compared.

Use Of Systems Approach with Total Quality Management in Industrial Organizations

The objective of the work has been to study why systems thinking should be used in combination with TQM, what are the main benefits of the integration and how it could best be done. The work analyzes the development of systems thinking and TQM with time and the main differences between them. The work defines prerequisites for adopting a systems approach and the organizational factors which embody the development of an efficient learning organization. The work proposes a model based on combination of an interactive management model and redesign to be used for application of systems approach with TQM in practice. The results of the work indicate that there are clear differences between systems thinking and TQM which justify their combination. Systems approach provides an additional complementary perspective to quality management. TQM is focused on optimizing operations at the operational level while interactive management and redesign of organization are focused on optimization operations at the conceptual level providing a holistic system for value generation. The empirical study demonstrates the applicability of the proposed model in one case study company but its application is tenable and possible also beyond this particular company. System dynamic modeling and other systems based techniques like cognitive mapping are useful methods for increasing understanding and learning about the behavior of systems. The empirical study emphasizes the importance of using a proper early warning system.

Effect of Potato virus X on total phenol and alkaloid contents in Datura stramonium leaves

The present paper reports results of the effect of Potato virus X (PVX) on the contents of total phenols and alkaloids in leaves of Datura stramonium. A significant decrease in the contents of phenols and alkaloids was observed in leaves inoculated with PVX (X-I). However, there was an increase in the percentage of phenols in leaves rubbed with phosphate buffer (C1-I) and in leaves from the nodes immediately above, possibly induced by mechanical injury. Gas chromatography/mass spectroscopy revealed amounts of scopolamine in samples submitted to all treatments, except X-I, in which the amount of this alkaloid was low. High amounts of an unidentified compound (molecular ion m/z 302 and a prominent peak at m/z 129) were noted in extracts from leaves X-I, C1-I and leaves from the nodes immediately above the leaves inoculated with PVX. It is suggested that the synthesis and accumulation of the unidentified compound is a result of stress from mechanical injury and virus inoculation.

Equivalence and translation strategies in multilingual thesaurus construction

In the present dissertation, multilingual thesauri were approached as cultural products and the focus was twofold: On the empirical level the focus was placed on the translatability of certain British-English social science indexing terms into the Finnish language and culture at a concept, a term and an indexing term level. On the theoretical level the focus was placed on the aim of translation and on the concept of equivalence. In accordance with modern communicative and dynamic translation theories the interest was on the human dimension. The study is qualitative. In this study, equivalence was understood in a similar way to how dynamic, functional equivalence is commonly understood in translation studies. Translating was seen as a decision-making process, where a translator often has different kinds of possibilities to choose in order to fulfil the function of the translation. Accordingly, and as a starting point for the construction of the empirical part, the function of the source text was considered to be the same or similar to the function of the target text, that is, a functional thesaurus both in source and target context. Further, the study approached the challenges of multilingual thesaurus construction from the perspectives of semantics and pragmatics. In semantic analysis the focus was on what the words conventionally mean and in pragmatics on the ‘invisible’ meaning - or how we recognise what is meant even when it is not actually said (or written). Languages and ideas expressed by languages are created mainly in accordance with expressional needs of the surrounding culture and thesauri were considered to reflect several subcultures and consequently the discourses which represent them. The research material consisted of different kinds of potential discourses: dictionaries, database records, and thesauri, Finnish versus British social science researches, Finnish versus British indexers, simulated indexing tasks with five articles and Finnish versus British thesaurus constructors. In practice, the professional background of the two last mentioned groups was rather similar. It became even more clear that all the material types had their own characteristics, although naturally not entirely separate from each other. It is further noteworthy that the different types and origins of research material were not used to represent true comparison pairs, and that the aim of triangulation of methods and material was to gain a holistic view. The general research questions were: 1. Can differences be found between Finnish and British discourses regarding family roles as thesaurus terms, and if so, what kinds of differences and which are the implications for multilingual thesaurus construction? 2. What is the pragmatic indexing term equivalence? The first question studied how the same topic (family roles) was represented in different contexts and by different users, and further focused on how the possible differences were handled in multilingual thesaurus construction. The second question was based on findings of the previous one, and answered to the final question as to what kinds of factors should be considered when defining translation equivalence in multilingual thesaurus construction. The study used multiple cases and several data collection and analysis methods aiming at theoretical replication and complementarity. The empirical material and analysis consisted of focused interviews (with Finnish and British social scientists, thesaurus constructors and indexers), simulated indexing tasks with Finnish and British indexers, semantic component analysis of dictionary definitions and translations, coword analysis and datasets retrieved in databases, and discourse analysis of thesauri. As a terminological starting point a topic and case family roles was selected. The results were clear: 1) It was possible to identify different discourses. There also existed subdiscourses. For example within the group of social scientists the orientation to qualitative versus quantitative research had an impact on the way they reacted to the studied words and discourses, and indexers placed more emphasis on the information seekers whereas thesaurus constructors approached the construction problems from a more material based solution. The differences between the different specialist groups i.e. the social scientists, the indexers and the thesaurus constructors were often greater than between the different geo-cultural groups i.e. Finnish versus British. The differences occurred as a result of different translation aims, diverging expectations for multilingual thesauri and variety of practices. For multilingual thesaurus construction this means severe challenges. The clearly ambiguous concept of multilingual thesaurus as well as different construction and translation strategies should be considered more precisely in order to shed light on focus and equivalence types, which are clearly not self-evident. The research also revealed the close connection between the aims of multilingual thesauri and the pragmatic indexing term equivalence. 2) The pragmatic indexing term equivalence is very much context-depended. Although thesaurus term equivalence is defined and standardised in the field of library and information science (LIS), it is not understood in one established way and the current LIS tools are inadequate to provide enough analytical tools for both constructing and studying different kinds of multilingual thesauri as well as their indexing term equivalence. The tools provided in translation science were more practical and theoretical, and especially the division of different meanings of a word provided a useful tool in analysing the pragmatic equivalence, which often differs from the ideal model represented in thesaurus construction literature. The study thus showed that the variety of different discourses should be acknowledged, there is a need for operationalisation of new types of multilingual thesauri, and the factors influencing pragmatic indexing term equivalence should be discussed more precisely than is traditionally done.

Differentiation of Colletotrichum gloeosporioides isolates by using total proteins and esterase electrophoretic patterns and extracellular enzymes production

Isolates of Colletotrichum gloeosporioides (ISO-1, ISO-2, ISO-3, ISO-4, ISO-5 and ISO-6), the causal agent of anthracnose disease on mango fruits, were characterized by electrophoretic patterns of total proteins and esterase in polyacrylamida gel, and also, by production of extracellular enzymes on specific solid substrate. The electrophoretic analysis showed variation in number, intensity of coloration and position of the bands in the gel at each studied system tested. In contrast to the monomorphic behavior to total proteins, high esterase polymorfism was observed indicating difference among isolates. All isolates showed the activity of extracellular enzymes such as amylase, lipase, and protease with some variation among them. The proteolitic activity seemed to be more accentuated than the two other enzymes studied.

First-Line Chemotherapy with Anthracycline and Taxane Combination in Metastatic Breast Cancer. Detection of bone metastases with TRACP 5b

Background: In Finland, breast cancer (BC) is the most common cancer among women, and prostate cancer (PC) that among men. At the metastatic stage both cancers remain essentially incurable. The goals of therapy include palliation of symptoms, improvement or maintenance of quality of life (QoL), delay of disease progression, and prolongation of survival. Balancing between efficacy and toxicity is the major challenge. With increasing costs of new treatments, appropriate use of resources is paramount. When new treatment regimes are introduced into clinical practice a comprehensive assessment of clinical benefit, adverse effects and cost is necessary. Both BC and PC show a predilection to metastasize to bone. Bone metastases cause significant morbidity impairing the patients´ QoL. Diagnosis of bone metastases relies mainly on radiological methods, which however lack optimal sensitivity and specificity. New tools are needed for detection and follow-up of bone metastases. Aims: Anthracyclines and taxanes are effective chemotherapeutic agents in the treatment of metastatic breast cancer (MBC) with different mechanisms of action. Therefore, evaluation of the combination of anthracyclines with taxanes was a justifiable approach in the treatment of MBC patients. We assessed the efficacy, toxicity, cost of treatment and QoL of BC patients treated with first-line chemotherapy for metastatic disease with the combination epirubicin and docetaxel. We also evaluated the diagnostic potential of tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptides of type I collagen (ICTP) in the diagnosis of bone metastases in BC and TRACP 5b in PC patients. Results: The combination of epirubicin and docetaxel was effective in this phase II study, but required individual dose adjustment to avoid neutropenic infections, and the use of growth factors to maintain a feasible dose level. The response rate was 54 % (95 % CI 37-71) and the median overall survival (OS) was 26 months. Of the patients, 87 % were treated for infections. The treatment of adverse events required additional use of health resources mainly due to neutropenic infections, thereby raising direct treatment costs by 20 %. Despite adverse events, the global QoL was not significantly compromised during the treatment. Clinically evident acute cardiac toxicity was not observed. The combination of serum TRACP 5b and ICTP was at least equally sensitive and specific in detection of of bone metastases as commonly used total alkaline phosphatise (tALP) in BC patients. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC patients. Conclusions: Treatment with epirubicin and docetaxel showed high efficacy in first-line chemotherapy of MBC. The relatively high incidence of neutropenic infections requiring hospitalization increased the treatment costs. Despite adverse events, the global QoL of the patients was not significantly compromised. The combination of TRACP 5b and ICTP showed similar activity as tALP in detecting bone metastases in MBC. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC.

Importância das variáveis altura dominante e altura total em equaçõea hipsométricas e volumétricas

Este estudo foi conduzido, visando avaliar as seguintes hipóteses: a) equações hipsométricas devem ser obtidas por parcela, apenas em função do dap; e b) equações volumétricas devem ser locais, em função apenas do dap. Foram utilizados dados de quatro parcelas distribuídas ao acaso em um povoamento de eucalipto de 67,81 ha e de 50 parcelas distribuídas ao acaso em um povoamento de 121,3 ha, da mesma espécie. Em uma análise inicial, a fim de obter valores reais de altura total e de volume sólido, realizou-se uma cubagem rigorosa de todas as árvores das quatro parcelas. Foram utilizados, ainda, dados de 277 árvores cubadas rigorosamente nos povoamentos. Para avaliar a exatidão das estimativas e as hipóteses formuladas, empregou-se o procedimento estatístico proposto por Leite & Oliveira (2002). Com base nos resultados, as hipóteses a e b foram rejeitadas a 1% de probabilidade. Concluiu-se, portanto, que em um inventário florestal a variável Hd deve ser considerada e que as equações volumétricas devem ser regionais.

Imazapyr root exudation from eucalypt seedlings cultivated in nutritive solution

Imazapyr has been used in Brazilian eucalypt cultivation for the maintenance of clearings and coppicing control in areas undergoing stand reform. However, inquiries have been made as to the final fate of the molecule. Imazapyr root exudation in eucalypt plants was evaluated through a bioassay under greenhouse conditions, by applying different herbicide doses (0.000, 0.375, 0.750, 1.125, and 1.500 kg ha-1 a.i.) on Eucalyptus grandis seedlings derived from vegetative propagation, hydroponically cultivated in 2.500 ml vases. Forty-day-old seedlings of the same clone were used as bioindicators, transplanted to the vases two days after herbicide application. After a period of 13 days of coexistence, the sprayed plants were removed and discarded; ten days later, the visual symptoms of toxicity were evaluated and the total dry biomass (aerial part and roots) of the bioindicators were determined. The lowest herbicide dose (0.375 kg ha-1 a.i.) affected the total biomass and growth, being most evident in the aerial part, with larger I50 for root dry biomass. The E. grandis seedlings exuded imazapyr, and/or its metabolites, in concentrations capable of affecting the growth of plants of the same species.

Modelo de predição para o volume total de Quaruba (Vochysia inundata ducke) via análise de fatores e regressão

Neste trabalho propôs-se um método para a construção de um modelo de regressão para determinar o Volume de Madeira Total da espécie florestal (Vochysia inundata ducke) Quaruba, em função de suas características (Diâmetro à Altura do Peito (DAP), Idade e Altura). O modelo foi determinado utilizando-se a técnica estatística multivariada de Análise de Fatores com do Método das Componentes Principais via Rotação Ortogonal do Tipo Varimax para Extração dos Fatores, procurando contornar o problema da Multicolinearidade. Por fim desenvolveu-se um modelo de Regressão Linear Simples com base nos Escores Fatoriais. O modelo determinado apresentou-se de fácil interpretação e utilização, usando-se um fator e proporcionando um bom ajuste (R² = 96 %) aos dados e uma boa capacidade preditiva. Ele atendeu a todas as suposições teóricas para sua existência e utilização.

Modelagem da biomassa total e da lenha por unidade de área para bracatingais nativos

A bracatinga (Mimosa scabrella Benth.) é uma espécie pioneira nativa da Floresta Ombrófila Mista de rápido crescimento e cultivada, predominantemente, na forma de povoamentos puros ou consorciada com culturas agrícolas pelos pequenos e médios produtores da região metropolitana de Curitiba. O objetivo deste estudo foi selecionar equações estimativas da biomassa total e da lenha de bracatingais por unidade de área nas diferentes idades, disponibilizando, assim, uma ferramenta simples e de fácil aplicação durante o processo de comercialização dos povoamentos. Os dados são provenientes de 272 parcelas temporárias com idades variando de 3 a 18 anos. Foram testados 21 modelos tradicionais: 10 aritméticos e semilogarítmicos e 11 logarítmicos. Foram também desenvolvidas equações pelo processo Stepwise a partir de uma matriz de correlação. As equações ajustadas foram comparadas pelo Coeficiente de determinação ajustado (R²aj), Erro-padrão da estimativa percentual (Syx%), teste F e Distribuição gráfica de resíduos. Duas equações para cada caso foram selecionadas, sendo uma tradicional e a outra desenvolvida por Stepwise. Para a biomassa total, foram selecionadas a equação de Clutter e a equação aritmética desenvolvida por Stepwise; e para a biomassa da lenha, a equação da variável combinada, proposta por Spurr, e a equação aritmética de Stepwise. Por fim, realizou-se teste Qui-quadrado (x²) a partir de uma amostra de 17 parcelas extraídas da base de dados, em que as quatro equações selecionadas foram consideradas válidas para a estimativa da biomassa total e da lenha dos bracatingais da região metropolitana de Curitiba.

Distribuição espacial das frações granulométricas argila e areia total em um Latossolo Vermelho-Amarelo

Este trabalho teve como objetivo estudar a variabilidade espacial das frações granulométricas argila e areia total de um Latossolo Vermelho-Amarelo cultivado com eucalipto. Amostras de solo foram coletadas nas profundidades de 0-0,20 m e 0,20-0,40 m em uma malha amostral de 33 x 33 m, totalizando 94 pontos georreferenciados. Os dados foram submetidos à análise estatística descritiva, geoestatística e interpolação por krigagem e cokrigagem. Na cokrigagem, utilizaram-se valores da profundidade de 0-0,20 m para estimar valores de 0,20-0,40 m. Maior valor médio da fração argila foi encontrado na profundidade de 0,20-0,40 m e na areia total, na profundidade de 0-0,20 m. O modelo esférico ajustou-se aos dados nos métodos de krigagem e cokrigagem. Os maiores alcances de dependência espacial foram encontrados na profundidade de 0,20-0,40 m. Os erros médios encontrados nos dois métodos apresentaram valores próximos e negativos, indicando superestimação dos valores amostrais.

Validação do modelo ClimaBR em relação ao número de dias chuvosos e à precipitação total diária

Este trabalho foi realizado com o objetivo de validar o modelo ClimaBR no que se refere à geração de séries sintéticas de precipitação total diária em diferentes localidades brasileiras. Para tanto, foram geradas séries sintéticas de precipitação para 12 localidades, escolhidas de forma distribuída, para que todas as diferentes regiões de precipitação homogênea do País fossem contempladas. A partir das séries pluviométricas, disponíveis nas estações meteorológicas das localidades selecionadas, o ClimaBR foi utilizado para gerar as séries sintéticas de precipitação, sendo gerada uma série de 100 anos para cada localidade. A qualidade dos resultados foi analisada comparando-se o ajuste entre os valores observados e os gerados pelo ClimaBR, por meio de regressão linear simples e de outros indicadores estatísticos. Os resultados obtidos permitem afirmar que, de acordo com as condições consideradas no presente estudo, o modelo ClimaBR apresentou bom desempenho na geração de séries sintéticas de precipitação (número de dias chuvosos e precipitação total diária) para todas as localidades testadas.

Receptores GPS de três precisões e estação total na caracterização de cotas básicas para projetos rurais

O objetivo deste estudo foi comparar cotas de vértices de uma poligonal, considerando dados coletados por três diferentes receptores GPS, usando como testemunha uma estação total. Os dados foram obtidos em uma poligonal fechada, sendo posteriormente tratados pelo software Topograph. As cotas obtidas pelos três receptores foram confrontadas com aquelas calculadas a partir do levantamento com a estação total, mediante a aplicação do teste "t", constatando-se que as mesmas foram satisfatórias para o equipamento GPS Trimble® 4600 LS. Para o equipamento GPS Trimble® modelo PRO XR, as cotas não foram totalmente satisfatórias, mas possíveis de serem consideradas em anteprojetos. Para o equipamento GPS Garmin® de navegação 12 XS, as cotas mostraram-se inaceitáveis para a finalidade estudada.