Biopharmaceutics classification system: importance and inclusion in biowaiver guidance

O tratamento farmacológico é essencial frente a várias patologias e é fundamental que a política de medicamentos tenha por objetivo oferecer à população tratamento seguro, eficaz e de preço acessível. Uma forma de alcançar esse objetivo é por meio da bioisenção, definida como a substituição de estudos de bioequivalência in vivo por estudos in vitro. Para bioisentar novos medicamentos sob a forma farmacêutica sólida oral de liberação imediata são utilizados dados de permeabilidade intestinal e solubilidade do fármaco, bem como sua dissolução a partir da forma farmacêutica. O Sistema de Classificação Biofarmacêutica (SCB) é um esquema científico que divide os fármacos em classes de acordo com a solubilidade e permeabilidade e vem sendo utilizado como critério para bioisenção em diversas legislações. O presente artigo faz uma avaliação da aplicação da bioisenção, abordando os conceitos gerais e parâmetros utilizados pelo SCB, fazendo um relato histórico da aplicação da bioisenção, das exigências pertinentes às legislações vigentes, dos benefícios e riscos inerentes a uma tomada de decisão sobre bioisenção baseada neste critério. Os resultados revelaram que a utilização do SCB como critério amplia enormemente as possibilidades de bioisenção, contribuindo para o maior acesso da população em geral a medicamentos com garantida eficácia, segurança e menor custo.Pharmacological therapy is essential in many diseases treatment and it is important that the medicine policy is intended to offering safe and effective treatment with affordable price to the population. One way to achieve this is through biowaiver, defined as the replacement of in vivo bioequivalence studies by in vitro studies. For biowaiver of new immediate release solid oral dosage forms, data such as intestinal permeability and solubility of the drug are required, as well as the product dissolution. The Biopharmaceutics Classification System (BCS) is a scientific scheme that divides drugs according to their solubility and permeability and has been used by various guides as a criterion for biowaiver. This paper evaluates biowaiver application, addressing the general concepts and parameters used by BCS, making a historical account of its use, the requirements pertaining to the current legislation, the benefits and risks associated with this decision. The results revealed that the use of BCS as a biowaiver criterion greatly expands the therapeutics options, contributing to greater therapy access of the general population with drug efficacy and safety guaranteed associated to low cost

Identification and expression analysis of microRNAs and targets in the biofuel crop sugarcane

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are small regulatory RNAs, some of which are conserved in diverse plant genomes. Therefore, computational identification and further experimental validation of miRNAs from non-model organisms is both feasible and instrumental for addressing miRNA-based gene regulation and evolution. Sugarcane (<it>Saccharum spp</it>.) is an important biofuel crop with publicly available expressed sequence tag and genomic survey sequence databases, but little is known about miRNAs and their targets in this highly polyploid species.</p> <p>Results</p> <p>In this study, we have computationally identified 19 distinct sugarcane miRNA precursors, of which several are highly similar with their sorghum homologs at both nucleotide and secondary structure levels. The accumulation pattern of mature miRNAs varies in organs/tissues from the commercial sugarcane hybrid as well as in its corresponding founder species <it>S. officinarum </it>and <it>S. spontaneum</it>. Using sugarcane <it>MIR827 </it>as a query, we found a novel <it>MIR827 </it>precursor in the sorghum genome. Based on our computational tool, a total of 46 potential targets were identified for the 19 sugarcane miRNAs. Several targets for highly conserved miRNAs are transcription factors that play important roles in plant development. Conversely, target genes of lineage-specific miRNAs seem to play roles in diverse physiological processes, such as <it>SsCBP1</it>. <it>SsCBP1 </it>was experimentally confirmed to be a target for the monocot-specific miR528. Our findings support the notion that the regulation of <it>SsCBP1 </it>by miR528 is shared at least within graminaceous monocots, and this miRNA-based post-transcriptional regulation evolved exclusively within the monocots lineage after the divergence from eudicots.</p> <p>Conclusions</p> <p>Using publicly available nucleotide databases, 19 sugarcane miRNA precursors and one new sorghum miRNA precursor were identified and classified into 14 families. Comparative analyses between sugarcane and sorghum suggest that these two species retain homologous miRNAs and targets in their genomes. Such conservation may help to clarify specific aspects of miRNA regulation and evolution in the polyploid sugarcane. Finally, our dataset provides a framework for future studies on sugarcane RNAi-dependent regulatory mechanisms.</p

Heteropoly acid catalysts in upgrading of biorenewables: Synthesis of para-menthenic fragrance compounds from α-pinene oxide

© 2018 Elsevier B.V. The isomerization of α-pinene oxide in the presence of Cs2.5H0.5PW12O40 (CsPW) heteropolysalt as solid acid catalyst is reported. The reactions were performed in various solvents, which allowed to obtain trans-carveol, trans-sobrerol and pinol in 60–80% yield each, which exceed the yields reported so far. The CsPW catalyst could be recovered and reused without loss of its activity and selectivity

The phases of deuterium at extreme densities

We consider deuterium compressed to higher than atomic, but lower than nuclear densities. At such densities deuterium is a superconducting quantum liquid. Generically, two superconducting phases compete, a "ferromagnetic" and a "nematic" one. We provide a power counting argument suggesting that the dominant interactions in the deuteron liquid are perturbative (but screened) Coulomb interactions. At very high densities the ground state is determined by very small nuclear interaction effects that probably favor the ferromagnetic phase. At lower densities the symmetry of the theory is effectively enhanced to SU(3), and the quantum liquid enters a novel phase, neither ferromagnetic nor nematic. Our results can serve as a starting point for investigations of the phase dynamics of deuteron liquids, as well as exploration of the stability and dynamics of the rich variety of topological objects that may occur in phases of the deuteron quantum liquid, which range from Alice strings to spin skyrmions to Z_2 vortices.Comment: 9 pages, 6 figures; v2: fixed typo

Fake News: propagación y comunidades, ¿Cuál es su relación?

El presente estudio investiga el creciente papel de las fake news en las comunidades digitales y el posible impacto resultado de su rápida propagación. Para ello, se usó la metodología netnográfica, junto con la observación lurking. Esta última se usó para preservar la integridad de los participantes. La recopilación de datos se enfocó en dos grupos políticos de ideologías similares con libre acceso en WhatsApp. Dichos datos permitieron una comprensión más detallada sobre la influencia de las fake news en la toma de decisiones, además de las posibles razones de su fácil y rápida propagación por internet

Transcriptome analysis of the oil-rich seed of the bioenergy crop Jatropha curcas L

<p>Abstract</p> <p>Background</p> <p>To date, oil-rich plants are the main source of biodiesel products. Because concerns have been voiced about the impact of oil-crop cultivation on the price of food commodities, the interest in oil plants not used for food production and amenable to cultivation on non-agricultural land has soared. As a non-food, drought-resistant and oil-rich crop, <it>Jatropha curcas </it>L. fulfils many of the requirements for biofuel production.</p> <p>Results</p> <p>We have generated 13,249 expressed sequence tags (ESTs) from developing and germinating <it>Jatropha </it>seeds. This strategy allowed us to detect most known genes related to lipid synthesis and degradation. We have also identified ESTs coding for proteins that may be involved in the toxicity of <it>Jatropha </it>seeds. Another unexpected finding is the high number of ESTs containing transposable element-related sequences in the developing seed library (800) when contrasted with those found in the germinating seed library (80).</p> <p>Conclusions</p> <p>The sequences generated in this work represent a considerable increase in the number of sequences deposited in public databases. These results can be used to produce genetically improved varieties of <it>Jatropha </it>with increased oil yields, different oil compositions and better agronomic characteristics.</p