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[Acte. 1544-1551]

Quantification of 4 antidepressants and a metabolite by LC-MS for therapeutic drug monitoring.

A liquid chromatography method coupled to mass spectrometry was developed for the quantification of bupropion, its metabolite hydroxy-bupropion, moclobemide, reboxetine and trazodone in human plasma. The validation of the analytical procedure was assessed according to Société Française des Sciences et Techniques Pharmaceutiques and the latest Food and Drug Administration guidelines. The sample preparation was performed with 0.5mL of plasma extracted on a cation-exchange solid phase 96-well plate. The separation was achieved in 14min on a C18 XBridge column (2.1mm×100mm, 3.5μm) using a 50mM ammonium acetate pH 9/acetonitrile mobile phase in gradient mode. The compounds of interest were analysed in the single ion monitoring mode on a single quadrupole mass spectrometer working in positive electrospray ionisation mode. Two ions were selected per molecule to increase the number of identification points and to avoid as much as possible any false positives. Since selectivity is always a critical point for routine therapeutic drug monitoring, more than sixty common comedications for the psychiatric population were tested. For each analyte, the analytical procedure was validated to cover the common range of concentrations measured in plasma samples: 1-400ng/mL for reboxetine and bupropion, 2-2000ng/mL for hydroxy-bupropion, moclobemide, and trazodone. For all investigated compounds, reliable performance in terms of accuracy, precision, trueness, recovery, selectivity and stability was obtained. One year after its implementation in a routine process, this method demonstrated a high robustness with accurate values over the wide concentration range commonly observed among a psychiatric population.

Splicing and the evolution of proteins in mammals.

It is often supposed that a protein's rate of evolution and its amino acid content are determined by the function and anatomy of the protein. Here we examine an alternative possibility, namely that the requirement to specify in the unprocessed RNA, in the vicinity of intron-exon boundaries, information necessary for removal of introns (e.g., exonic splice enhancers) affects both amino acid usage and rates of protein evolution. We find that the majority of amino acids show skewed usage near intron-exon boundaries, and that differences in the trends for the 2-fold and 4-fold blocks of both arginine and leucine show this to be owing to effects mediated at the nucleotide level. More specifically, there is a robust relationship between the extent to which an amino acid is preferred/avoided near boundaries and its enrichment/paucity in splice enhancers. As might then be expected, the rate of evolution is lowest near intron-exon boundaries, at least in part owing to splice enhancers, such that domains flanking intron-exon junctions evolve on average at under half the rate of exon centres from the same gene. In contrast, the rate of evolution of intronless retrogenes is highest near the domains where intron-exon junctions previously resided. The proportion of sequence near intron-exon boundaries is one of the stronger predictors of a protein's rate of evolution in mammals yet described. We conclude that after intron insertion selection favours modification of amino acid content near intron-exon junctions, so as to enable efficient intron removal, these changes then being subject to strong purifying selection even if nonoptimal for protein function. Thus there exists a strong force operating on protein evolution in mammals that is not explained directly in terms of the biology of the protein.

The control of microtubule stability in vitro and in transfected cells by MAP1B and SCG10.

In neurons, the regulation of microtubules plays an important role for neurite outgrowth, axonal elongation, and growth cone steering. SCG10 family proteins are the only known neuronal proteins that have a strong destabilizing effect, are highly enriched in growth cones and are thought to play an important role during axonal elongation. MAP1B, a microtubule-stabilizing protein, is found in growth cones as well, therefore it was important to test their effect on microtubules in the presence of both proteins. We used recombinant proteins in microtubule assembly assays and in transfected COS-7 cells to analyze their combined effects in vitro and in living cells, respectively. Individually, both proteins showed their expected activities in microtubule stabilization and destruction respectively. In MAP1B/SCG10 double-transfected cells, MAP1B could not protect microtubules from SCG10-induced disassembly in most cells, in particular not in cells that contained high levels of SCG10. This suggests that SCG10 is more potent to destabilize microtubules than MAP1B to rescue them. In microtubule assembly assays, MAP1B promoted microtubule formation at a ratio of 1 MAP1B per 70 tubulin dimers while a ratio of 1 SCG10 per two tubulin dimers was needed to destroy microtubules. In addition to its known binding to tubulin dimers, SCG10 binds also to purified microtubules in growth cones of dorsal root ganglion neurons in culture. In conclusion, neuronal microtubules are regulated by antagonistic effects of MAP1B and SCG10 and a fine tuning of the balance of these proteins may be critical for the regulation of microtubule dynamics in growth cones.

Rabani Mauri in Ecclesiasticum commentarii : recens in lucem editi ([Reprod.])

Collection : French books before 1601 ; 67.7

FORMAÇÃO DE OPERADORES E TÉCNICOS DO SECTOR DAS PESCAS

O presente documento tem como objectivo apresentar a actuação do INDP na área de formação de operadores de pescas e técnicos ligados ao sector, bem como a metodologia adoptada e os principais resultados atingidos com a elaboração e execução do plano de formação referente ao ano de 2007 e 2008. Trata-se de uma apreciação quantitativa em termos de número de formandos e acções de formação que o INDP tem vindo a implementar no seio do sector das pescas em Cabo Verde. Pela análise realizada, com base na execução do último plano de formação ficou-se claro que, para além de os planos terem sidos elaborados com uma abrangência nacional e com objectivos claros visando atingir o maior número possível de operadores e técnicos ligados ao sector, nem sempre este objectivo é atingido, pois na prática a realidade é outra. Verificou-se uma fraca implementação do plano de formação em questão e isso poderá ser explicada pelos inúmeros constrangimentos abordados no corpo do documento, que tem vindo a perturbar o sucesso da actuação do INDP neste domínio. Pela comparação estabelecida entre as actividades projectadas e as realmente realizadas pode-se dizer que a execução do plano foi abaixo dos 50 %, o que poderá levar o INDP, a rever a sua estratégia de intervenção neste domínio.

Family physician involvement in cancer care follow-up: the experience of a cohort of patients with lung cancer.

PURPOSE There has been little research describing the involvement of family physicians in the follow up of patients with cancer especially during the primary treatment phase We undertook a prospective longitudinal study of patients with lung cancer to assess their family physician s involvement in their follow up at the different phases of cancer METHODS In 5 hospitals in the province of Quebec Canada patients with a recent diagnosis of lung cancer were surveyed every 3 to 6 months whether they had metastasis or not, for a maximum of 18 months to assess aspects of their family physician s involvement in cancer care RESULTS Of the 395 participating patients 92% had a regular family physician but only 60% had been referred to a specialist by him/her or a colleague for the diagnosis of their lung cancer A majority of patients identified the oncology team or oncologists as mainly responsible for their cancer care throughout their cancer journey except at the advanced phase where a majority attributed this role to their family physician At baseline only 16% of patients perceived a shared care pattern between their family physician and oncologists but this pro portion increased with cancer progression Most patients would have liked their family physician to be more involved in all aspects of cancer care CONCLUSIONS Although patients perceive that the oncology team is the main party responsible for the follow up of their lung cancer they also wish their family physicians to be involved Better communication and collaboration between family physicians and the oncology team are needed to facilitate shared care in cancer follow up

El fitoplancton superficial durante el crucero de evaluación hidroacústica de recursos pelágicos en el invierno 1998

Describe los volúmenes de plancton, la distribución, composición e indicadores del fitoplancton de superficie el Crucero de Evaluación Hidroacústica de Recursos Pelágicos 9808-09. Los volúmenes de plancton estuvieron en un rango de 0,01 a 23,3 mL/m3; el primero en la estación costera al norte de Pimentel y el otro al frente de Matarani, con un promedio de 1,16 mL/m3. Se apreció un elevado porcentaje (73%) con valores menores a 1,0 mL/m3. La comunidad planctónica fue muy variada, destacando diferentes organismos del zooplancton. En el fitoplancton resaltaron especies neríticas y de alta tasa de reproducción; diatomeas oceánicas predominaron a distancias mayores de 60 mn. Los dinoflagelados no abundaron pero se distribuyeron ampliamente con mayor riqueza de especies termófilas a distancias mayores de 30 mn.

Reliure de : ... @Prophetae priores. Josue. Judicum liber. Samuel. Regum II

[Bible. A.T. (hébreu). 1539-1544. 2]

Reliure de : Epistolarum ad Atticum, ad Brutum, ad Quintum fratrem, libri XX...

Numérisation partielle de reliure