Precios de los medicamentos: cómo se establecen y cuáles son sus sistemas de control / Drug prices: how they are established and existing price control systems

El precio es una de las principales barreras de acceso a los medicamentos. Por ello es importante conocer cómo se forman los precios y qué factores determinan su cuantía y también qué formas de intervención y regulación son las más adecuadas teniendo en cuenta sus efectos, tanto sobre el acceso, como sobre la innovación, la producción local y otros posibles objetivos de la política de medicamentos. El análisis económico ha desarrollado un conjunto de modelos de mercado que permiten explicar el comportamiento de los precios, aunque los mercados reales divergen sustancialmente de los modelos teóricos. La regulación de precios está justificada por los llamados "fallos de mercado"; la regulación de precios basada en el costo de producción, la modalidad de control de precios más tradicional, ha caído en desuso a favor de los sistemas de precios de referencia internacionales y por la fijación del precio basada en el valor.

Price is one of the main barriers of access to medicines. It is therefore important to understand how prices are formed and what factors determine the amount, as well as what interventions and regulations are the most appropriate considering their effects on access, innovation, local production and other potential objectives of drug policy. Economic analysis has developed a set of market models that can explain the behavior of prices, although actual markets diverge substantially from the theoretical models. Price regulation is justified by the so-called "market failures." Price regulation based on the cost of production, the most traditional form of price control, has fallen into disuse in favor of systems of international reference pricing and value-based pricing.

Prophylactic treatment with Bacopa monnieri leaf powder mitigates paraquat- induced oxidative perturbations and lethality in Drosophila melanogaster.

Environmental exposure to the oxidant-producing herbicide, paraquat (PQ) (1, 1’-dimethyl-4, 4’-bipyridinium dichloride) has long been implicated as a risk factor in Parkinson’s disease (PD). PQ-induced oxidative stress has been exploited as a model to screen putative neuroprotective compounds employing Drosophila. In the present study, we investigated the prophylactic efficacy of Bacopa monnieri (BM) against PQ-induced oxidative stress, mitochondrial dysfunctions and lethality. Exposure of adult male flies (Oregon K) to PQ alone (40 mM in 5% sucrose) resulted in 50% mortality at 48 h. Prophylaxis (7 days) with BM extract (0.1%) offered significant protection (40%) against PQ-induced mortality. Further, oxidative impairments and mitochondrial dysfunctions were monitored among Drosophila exposed to PQ (20, 40 mM) for 24 h. Significant induction of oxidative stress was observed in terms of enhanced malondialdehyde and hydroperoxide levels, and elevated activities of antioxidant enzymes (catalase and SOD). Mitochondrial dysfunctions included of significant reduction in the activities of succinate dehydrogenase (23%), complex I-III (26%), and complex II-III (30%) enzymes. Interestingly, prophylaxis with BM extract prevented the oxidative stress induction by PQ and restored the activity of ETC complexes, suggesting clearly its specific effect on the mitochondria. While the precise mechanism of action of BM needs further investigations, it may be related to its ability to enhance antioxidant defences and thus mitigate PQ-induced oxidative stress in Drosophila.

Formal TCA cycle description based on elementary actions.

Many databases propose their own structure and format to provide data describing biological processes. This heterogeneity contributes to the difficulty of large systematic and automatic functional comparisons. To overcome these problems, we have used the BioPsi formal description scheme which allows multi-level representations of biological process information. Applied to the description of the tricarboxylic acid cycle (TCA), we show that BioPsi allows the formal integration of functional information existing in current databases and make them available for further automated analysis. In addition such a formal TCA cycle process description leads to a more accurate biological process annotation which takes in account the biological context. This enables us to perform an automated comparison of the TCA cycles for seven different species based on processes rather than protein sequences. From current databases, BioPsi is able to unravel information that are already known by the biologists but are not available for automated analysis tools and simulation software, because of the lack of formal process descriptions. This use of the BioPsi description scheme to describe the TCA cycle was a key step of the MitoScop project that aims to describe and simulate mitochondrial metabolism in silico.

Molecular population genetics of the beta-esterase gene cluster of Drosophila melanogaster.

We have investigated nucleotide polymorphism at the beta-esterase gene cluster including the Est-6 gene and psiEst-6 putative pseudogene in four samples of Drosophila melanogaster derived from natural populations of southern Africa (Zimbabwe), Europe (Spain), North America (USA: California), and South America (Venezuela). A complex haplotype structure is revealed in both Est-6 and psiEst-6. Total nucleotide diversity is twice in psiEst-6 as in Est-6; diversity is higher in the African sample than in the non-African ones. Strong linkage disequilibrium occurs within the beta-esterase gene cluster in non-African samples, but not in the African one. Intragenic gene conversion events are detected within Est-6 and, to a much greater extent, within psiEst-6; intergenic gene conversion events are rare. Tests of neutrality with recombination are significant for the beta-esterase gene cluster in the non-African samples but not significant in the African one. We suggest that the demographic history (bottleneck and admixture of genetically differentiated populations) is the major factor shaping the pattern of nucleotide polymorphism in the beta-esterase gene cluster. However there are some 'footprints' of directional and balancing selection shaping specific distribution of nucleotide polymorphism within the cluster. Intergenic epistatic selection between Est-6 and psiEst-6 may play an important role in the evolution of the beta-esterase gene cluster preserving the putative pseudogene from degenerative destruction and reflecting possible functional interaction between the functional gene and the putative pseudogene. Est-6 and psiEst-6 may represent an indivisible intergenic complex ('intergene') in which each single component (Est-6 or psiEst-6) cannot separately carry out the full functional role.