Clinically significant drug interactions with agents specific for migraine attacks

The drugs which provide specific relief from migraine attacks, the ergopeptides (ergotamine and dihydroergotamine) and the various 'triptans' (notably sumatriptan), are often prescribed for persons already taking various migraine preventative agents, and sometimes drugs for other indications. As a result, migraine-specific drugs may become involved in drug-drug interactions. The migraine-specific drugs all act as agonists at certain subclasses of serotonin (5-hydroxytryptamine; 5-MT) receptor, particularly those of the 5-HT1D subtype, and produce vasoconstriction through these receptor-mediated mechanisms. The oral bioavailabilities of these drugs, particularly those of the ergopeptides, are often incomplete, due to extensive presystemic metabolism. As a result, if migraine-specific agents are coadministered with drugs with vasoconstrictive properties, or with drugs which inhibit the metabolism of the migraine-specific agents, there is a risk of interactions occurring which produce manifestations of excessive vasoconstriction. This can also occur through pharmacodynamic mechanisms, as when ergopeptides or triptans are coadministered with methysergide or propranolol (although a pharmacokinetic element may apply in relation to the latter interaction), or if one migraine-specific agent is used shortly after another. When egopeptide metabolism is inhibited by the presence of macrolide antibacterials, particularly troleandomycin and erythromycin, the resultant interaction can produce ergotism, sometimes leading to gangrene. Similar pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably apply to combination of the ergopeptides with HIV protease inhibitors (indinavir and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise circulating triptan concentrations, although this does not yet seem to have led to reported clinical problems. Caffeine may cause increased plasma ergotamine concentrations through an as yet inadequately defined pharmacokinetic interaction. However, a direct antimigraine effect of caffeine may contribute to the claimed increased efficacy of ergotamine-caffeine combinations in relieving migraine attacks. Serotonin syndromes have been reported as probable pharmacodynamic consequences of the use of ergots or triptans in persons taking serotonin reuptake inhibitors. There have been two reports of involuntary movement disorders when sumatriptan has been used by patients already taking loxapine. Nearly all the clinically important interactions between the ergopeptide antimigraine agents and currently marketed drugs are likely to have already come to notice. In contrast, new interactions involving the triptans are likely to be recognised as additional members of this family of drugs, with their different patterns of metabolism and pharmacokinetics, are marketed.

Laboratory evaluation of two native fishes from tropical North Queensland as biological control agents of subterranean Aedes aegypti

The ability of 2 freshwater fishes, eastern rainbow fish Melanotaenia splendida splendida and fly-specked hardyhead Craterocephalus stercusmuscarum stercusmuscarum. native to North Queensland to prey on immature Aedes aegypti was evaluated under laboratory conditions. The predation efficiency of the 2 species was compared to the exotic guppy, Poecilia reticulata, which is commonly used as a biological control agent of mosquito larvae. Of the 3 fish species tested, M. s. splendida was shown to be the most promising agent for the biological control of Ae. aegypti that breed in wells. Melanotaenia s. splendida consumed significantly greater numbers of immature Ae. aegypti than P. reticulata, irrespective of developmental stage or light conditions. Unlike C. s. stercusmuscarum, M, s. splendida could be handled, transported, and kept in captivity for extended periods with negligible mortality. However, M. s. splendida was also an efficient predator of Litoria caerulea tadpoles, a species of native frog found in wells during the dry season. This result may limit the usefulness of M. s. splendida as a biological control agent of well-breeding Ae. aegypti and suggests that predacious copepods, Mesocyclops spp., are more suitable. However, the use of M. s. splendida as a mosquito control agent in containers that are unlikely to support frog populations (e.g., aquaculture tanks and drinking troughs) should be given serious consideration.

Agents as multi-threaded logical objects

In this paper we describe a distributed object oriented logic programming language in which an object is a collection of threads deductively accessing and updating a shared logic program. The key features of the language, such as static and dynamic object methods and multiple inheritance, are illustrated through a series of small examples. We show how we can implement object servers, allowing remote spawning of objects, which we can use as staging posts for mobile agents. We give as an example an information gathering mobile agent that can be queried about the information it has so far gathered whilst it is gathering new information. Finally we define a class of co-operative reasoning agents that can do resource bounded inference for full first order predicate logic, handling multiple queries and information updates concurrently. We believe that the combination of the concurrent OO and the LP programming paradigms produces a powerful tool for quickly implementing rational multi-agent applications on the internet.

Exotic vs endemic biocontrol agents: Would the real stratiolaelaps miles (Berlese) (Acari : Mesostigmata : Laelapidae), please stand up?

The ability of introduced organisms to invade undisturbed native habitats is a major concern in conservation biology and has resulted in a re-evaluation of the introduction of exotic biocontrol agents, especially of generalist predators. One such agent is Stratiolaelaps miles (Berlese), a predatory mite described from Italy, known from throughout the Holarctic, and apparently accidentally introduced to other areas of the world, including Australia. Initial investigations revealed that putative S. miles could be found in both disturbed and relatively pristine habitats in Queensland, Australia. However, analysis of the mitochondrial DNA of five populations showed most to be highly divergent genetically. Subsequent morphological analysis established two species groups: the lamington-group from cool-temperate to subtropical rainforests in Eastern Australia and the more eurytopic miles-group with a cosmopolitan distribution. We describe two new species from each of these complexes (Stratiolaelaps womersleyi, Stratiolaelaps lamington; Stratiolaelaps marilyn, Stratiolaelaps lorna, respectively), and resurrect Stratiolaelaps scimitus (Womersley), a species which often appears to have been confused with S. miles. Additionally, the large genetic distances among morphologically homogenous species in the miles-group suggest that the apparently cosmopolitan S. miles may be composed of a suite of cryptic species of potentially varying utility in biological control. (C) 2002 Elsevier Science (USA). All rights reserved.

Evaluation of potential biocontrol agents against Claviceps africana in vitro and in vivo

Undiluted culture filtrates of two commercial products of Trichoderma spp., Trichopel and Trichoflow, and two isolates of Penicillium citrinum completely inhibited the conidial germination of macroconidia of Claviceps africana , the cause of ergot or sugary disease of sorghum (Sorghum bicolor) in vitro . Similarly, Pseudomonas aeruginosa and Burkholderia cepacia completely inhibited macroconidial germination, with the former being more effective at high dilutions. In contrast, these bacterial isolates failed to inhibit infection in vivo in glasshouse tests with ergot-inoculated sorghum, but all fungal biocontrol agents (including an isolate of Epicoccum nigrum) reduced the severity of disease (percentage of infected spikelets per panicle), in some cases completely inhibiting the development of ergot. In a second glasshouse trial, optimum control was achieved when the biocontrol agents were applied 3-7 days before inoculation with conidia of C. africana .

Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group

Background: There is ample evidence of important symptomatic efficacy of tumour necrosis factor alpha (TNFalpha) inhibition in ankylosing spondylitis (AS). Moreover, studies suggest that anti-TNF could be considered as the first disease controlling antirheumatic treatment (DC-ART) for AS. Objective: To determine precisely which patients with AS are most likely to benefit from anti-TNFalpha treatment because of the cost and possible long term side effects of such treatment. Methods: Assessment in Ankylosing Spondylitis (ASAS) members were asked to use a Delphi technique to name the characteristics of patients with AS for whom they would start DC-ART, in three different clinical presentations (isolated axial involvement, peripheral arthritis, enthesitis). Results: Among the 62 invited ASAS members, more than 50% actively participated in the four phases of definition according to the Delphi technique. For each of the three clinical presentations, a combination of five to six domains was proposed, with an evaluation instrument and a cut off point defining a minimum level of activity for each domain. Conclusion: This study provides a profile for a patient with AS for considering initiation of biological agents that reflects the opinion of the ASAS members, using a Delphi exercise. Further studies are required to assess their relevance and their consistency with clinical practice.

Plano de implementa????o do projeto de desenvolvimento de capacidade de governan??a

Desde a d??cada de 1990, o Governo Federal brasileiro vem implementando uma agenda ambiciosa de reformas do Estado, centradas na redu????o da pobreza e na melhoria da efici??ncia dos servi??os p??blicos. As principais prioridades, conforme previstas no Plano Plurianual (PPA) para o per??odo 2003-2007, s??o as seguintes: inclus??o social e redu????o da desigualdade; crescimento econ??mico com gera????o de emprego; distribui????o de renda e respeito ao meio ambiente; promo????o e amplia????o dos direitos de cidadania; e fortalecimento da democracia. No in??cio de 2006, o Governo criou a Pol??tica Nacional de Desenvolvimento de Pessoal (Decreto 5.707), com o objetivo de melhorar e aumentar a efici??ncia e a efic??cia na presta????o de servi??os p??blicos. No marco dessa pol??tica recente, as escolas de administra????o p??blica desempenham um papel fundamental na identifica????o das compet??ncias que precisam ser desenvolvidas nas institui????es do governo, bem como na implementa????o de pol??ticas de capacita????o para os servidores p??blicos, diretamente e/ou em parceria com escolas de governo nos n??veis federal, estadual ou local. O Canad?? tamb??m est?? criando uma estrutura para levantar as compet??ncias necess??rias para os servidores p??blicos e desenvolv??-las como um componente da Renova????o do Servi??o P??blico em todo o governo. Como institui????es l??deres no desenvolvimento de compet??ncias de servidores p??blicos, a Canada School of Public Service (CSPS) e a Escola Nacional de Administra????o P??blica (ENAP) firmaram uma parceria para implementar o Projeto de Desenvolvimento de Capacidade de Governan??a no Brasil. A finalidade do Projeto ?? melhorar a capacidade de servidores p??blicos federais, estaduais e municipais do Brasil para desenvolver e implementar programas de capacita????o e gerenciar pol??ticas p??blicas descentralizadas. Espera-se que essa parceria e o resultante compartilhamento de experi??ncias em capacita????o para governan??a efetiva contribuam para a redu????o da pobreza e das desigualdades no Brasil, por meio do desenvolvimento de compet??ncias de servidores na presta????o de servi??os p??blicos eficazes e eficientes, voltados para o cidad??o. O Projeto re??ne, al??m das duas principais Escolas de Governo no Canad?? e no Brasil, seis Escolas Brasileiras de Administra????o P??blica regionais e duas renomadas Institui????es Acad??micas Canadenses ??? a Queen???s University e a Western Ontario University. O Minist??rio do Desenvolvimento Social e Combate ?? Fome (MDS) e tr??s Secretarias Especiais do Governo Federal ??? Ra??a (SEPPIR), Direitos Humanos (SEDH) e Pol??ticas para as Mulheres (SPM) ??? tamb??m se envolver??o nas atividades de compartilhamento de conhecimentos com o Human Resources and Skills Development Canada (HRSDC) e a Canada Public Service Agency (CPSA). A CIDA fornecer?? CND$1.700.000 por meio do Programa Brasil-Canad?? de Interc??mbio de Conhecimentos para a Promo????o da Equidade (PIPE). A contribui????o da ENAP ser?? de CND$1.069.707 em esp??cie. A CSPS contribuir?? com cursos, al??m de conhecimentos e suporte t??cnicos, avaliados em CND$1.000.000. Aproveitando a parceria entre a CSPS e a ENAP, que resultou na transfer??ncia e na adapta????o bem sucedidas de cursos e metodologias canadenses, o novo projeto extrapola o n??cleo do servi??o p??blico em Bras??lia, alcan??ando escolas de governo em regi??es brasileiras em situa????o de desvantagem. ?? semelhan??a do papel da CSPS no primeiro projeto, a ENAP fortalecer?? a capacidade das escolas parceiras regionais para capacitar servidores p??blicos envolvidos na presta????o de servi??os aos brasileiros. O interc??mbio estruturado entre Minist??rios dos Governos canadense e brasileiro tamb??m aplicar?? a aprendizagem mais diretamente a quest??es de pol??ticas e programas sociais do Brasil. O desafio assumido neste Projeto ?? a adapta????o de conhecimentos e aprendizagem, com vistas a melhorar a implementa????o de pol??ticas e programas sociais. Para tanto, a CSPS e a ENAP introduzir??o novos cursos nos curr??culos das escolas parceiras e incorporar??o novos m??todos e tecnologias de aprendizagem como, por exemplo, comunidades de pr??tica virtuais e um componente de tutoria (mentoring) envolvendo o Human Resources and Skills Development Canada e o Minist??rio do Desenvolvimento Social e Combate ?? Fome do Brasil. Seis institui????es da Rede Nacional de Escolas de Governo do Brasil e do Programa de Parceria da ENAP foram selecionadas e convidadas a se unir ?? CSPS e ?? ENAP nesse novo Projeto: a Universidade Federal do Par?? (UFPA), de Bel??m (estado do Par?? ??? regi??o Norte); a Funda????o Joaquim Nabuco (FUNDAJ), de Recife (Pernambuco ??? Nordeste); a Universidade Corporativa do Servi??o P??blico / Secretaria de Administra????o do Estado da Bahia (UCS/SAEB), Salvador (Bahia ??? Nordeste); a Escola de Governo do Mato Grosso do Sul (ESCOLAGOV), Campo Grande (estado do Mato Grosso do Sul ??? Centro-Oeste); a Escola Nacional de Ci??ncias Estat??sticas / Instituto Brasileiro de Geografia e Estat??stica (ENCE/IBGE), Rio de Janeiro (estado do Rio de Janeiro ??? Sudeste); e o Instituto Municipal de Administra????o P??blica (IMAP) de Curitiba (Paran?? ??? Sul). Essas escolas de refer??ncia foram escolhidas segundo sua capacidade de trabalhar como p??los de pr??ticas inovadoras em pol??ticas p??blicas e disseminar os benef??cios do Projeto para outras escolas em suas regi??es, por meio da Rede Nacional coordenada pela ENAP. O objetivo dessa parceria ?? fortalecer as escolas de governo locais, para que estas desenvolvam, por meio de eventos de aprendizagem, compet??ncias em servidores p??blicos, a fim de aumentar a capacidade do governo na implementa????o e gest??o de pol??ticas p??blicas. O Plano de Implementa????o do Projeto (PIP) descreve o trabalho a ser realizado por essas institui????es nos pr??ximos 30 meses, ao tempo em que serve de guia para os Parceiros do Projeto no que se refere ??s a????es e aos recursos necess??rios para a obten????o dos resultados acordados. Na medida em que o Projeto estiver em andamento e os parceiros iniciarem um interc??mbio produtivo de conhecimentos, o Plano de Trabalho Anual ser?? atualizado e revisto por meio de reuni??es anuais de avalia????o e encontros do Comit?? Diretor do Projeto, com vistas a assegurar que os resultados descritos no PIP sejam alcan??ados com sucesso

Fatores intervenientes na implementação de ações estratégicas para a promoção do selo de indicação geográfica das panelas de barro de goiabeiras

Visando a proteção da propriedade industrial advinda de uma região demarcada, surgiu a Indicação Geográfica (IG). O registro da IG é conferido aos produtos ou serviços característicos de seu local de origem, apresentando qualidades únicas em função dos recursos naturais. Além disso, a IG é responsável por distinguir estes produtos em relação aos disponíveis no mercado. Neste contexto, entidades como Sebrae, MAPA e INPI, têm promovido ações estratégicas com o objetivo de apoiar a proteção do saber fazer e consequentemente, os produtos tradicionais das regiões. Tais entidades são responsáveis por promover a sustentabilidade do processo juntos aos produtores, assim como disseminar o selo para os consumidores. Assim, iniciativas como esta precisam ser apoiadas a fim de entregar resultados significativos para o desenvolvimento das regiões e seus respectivos produtos com o selo de IG. O Plano de Apoio à Gestão da Indicação Geográfica desenvolvido pelo Sebrae/ES tem três pilares: melhoria do processo de produção, promoção do produto e a sustentabilidade do processo. A presente pesquisa, baseando-se nas teorias sobre estratégia e implementação de estratégias, analisa os fatores intervenientes que contribuem para o sucesso da implementação do Plano de Apoio à Gestão da indicação geográfica das Panelas de Barro de Goiabeiras, bairro do município de Vitória, capital do Espírito Santo. A pesquisa é um estudo de caso de natureza qualitativa, exploratória e descritiva ex-post-facto. Os dados foram coletados nos documentos (plano de ação do Sebrae/ES, Livro dos Saberes e relatórios desenvolvidos por consultores especializados) e por meio de entrevistas com seis agentes de políticas públicas e cinco paneleiras, envolvidos na elaboração e implementação do plano de ação. Para a análise dos dados, adotou-se a metodologia de análise de conteúdo com index definido a posteriori. Do Plano de Apoio à Gestão da IG das Paneleiras de Goiabeiras, foram agrupadas três ações estratégicas buscando identificar em que medida os fatores intervenientes afetaram a implementação de cada ação estudada: Ação1: fortalecimento dos aspectos culturais do produto, Ação 2: fortalecimento dos aspectos sociais do produto e Ação 3: fortalecimento dos aspectos econômicos associados à diferenciação por IG. Os resultados mostraram que na Ação 1 o fator interveniente liderança superou as expectativas na implementação das estratégias. Já os aspectos políticos, o acompanhamento de resultados e a estrutura organizacional desenvolveram as ações conforme o planejado, enquanto os fatores intervenientes cultura e clareza nas estratégias apresentaram oportunidades de melhorias. Na Ação 2 somente os fatores intervenientes recursos, cultura e clareza nas estratégias apresentaram-se de acordo com o proposto, enquanto a liderança e a estrutura organizacional mostraram-se como pontos de oportunidades de melhoria. Por fim, na Ação 3 nenhum fator interveniente foi destaque como uma oportunidade de melhoria. A estrutura organizacional e os aspectos políticos apresentaram-se de acordo, enquanto os recursos e a liderança superaram as expectativas.

Towards an uncertain future? The strengthening of Japan's autonomy in Asia-Pacific

Recently, Japan has been increasing tensions with China regarding the Pinnacle Senkaku/Diaoyu islands. Due to the Chinese military development, Japan has been working on its political and military strengthening in Asia. This essay presents two possible scenarios for Japan.

Multi-level governance and social cohesion in the European Union: the assessment of local agents, a study case inside Galicia

Implementing multi-level governance has been a key priority in EU cohesion policy. This study assesses the perceived achievements and shortcomings in implementing European Social Fund by analyzing the deficits and weaknesses as well as the poor participation of local agents who are in direct contact with the beneficiaries in order to design and implement this fund, which is the main financial instrument of EU social policy.

Biochemical and morpho-anatomical analyses of strawberry vitroplants hyperhydric tissues affected by BA and gelling agents

In vitro propagation has become an effective practice for large-scale production of strawberry plants. The objective of this study was to evaluate the hyperhydricity and the multiplication capacity of two strawberry varieties (Fragaria x ananassa Duch. 'Dover' and 'Burkley') propagated in vitro. Plants maintained in MS medium supplemented with 1.0 mg L-1 BA were individualized and transferred to the same medium solidified with Agar (6.5 g L-1) or Phytagel® (2.5 g L-1) and BA at different concentrations (0; 0.5; 1.0; 2.0 and 3.0 mg L-1). Biochemical and anatomical analyses were carried out, as well as the analysis of the morphological hyperhydricity characteristics. The analysis of data showed: a) the increase in cytokinin concentration increased hyperhydricity frequency in both varieties; b) at concentrations up to 2.0 mg L-1 BA, the replacement of Agar by Phytagel® induced a higher formation of hyperhydric shoots; and c) the addition of BA induced oxidative stress, which is characterized by increased antioxidant activity and lipid peroxidation, as well as alterations at the cellular level, such as malformation of stomata and epidermal cells. In conclusion, the culture medium containing 0.5 mg L-1 BA solidified with Agar provided lower hyperhydricity percentages in association with higher rates of shoot proliferation in strawberry.

(Virtual) Agents for running electricity markets

This paper describes a multi-agent based simulation (MABS) framework to construct an artificial electric power market populated with learning agents. The artificial market, named TEMMAS (The Electricity Market Multi-Agent Simulator), explores the integration of two design constructs: (i) the specification of the environmental physical market properties and (ii) the specification of the decision-making (deliberative) and reactive agents. TEMMAS is materialized in an experimental setup involving distinct power generator companies that operate in the market and search for the trading strategies that best exploit their generating units' resources. The experimental results show a coherent market behavior that emerges from the overall simulated environment.

Genotoxicity biomarkers: application in histopathology laboratories

Most cancers results from man-made and natural environmental exposures (such as tobacco smoke; chemical pollutants in air, water, food, drugs; radon; and infectious agents) acting in concert with both genetic and acquired characteristics. It has been estimated that without these environmental factors, cancer incidence would be dramatically reduced, by as much as 80%-90%. The modulation of environmental factors by host susceptibility was rarely evaluated. However, within the past few years, the interaction between environmental factors and host susceptibility factors has become a very active area of research. Molecular biology as a tool for use in epidemiological studies has significant potential in strengthening the identification of cancers associated with environmental exposures related to lifestyle, occupation, or ambient pollution. In molecular epidemiology, laboratory methods are employed to document the molecular basis and preclinical effects of environmental carcinogenesis. Molecular epidemiology has become a major field of research and considerable progress has been made in validation and application of biomarkers and its greatest contribution has been the insights provided into interindividual variation in human cancer risk and the complex interactions between environmental factors and host susceptibility factors, both inherited and acquired, in the multistage process of carcinogenesis.