Human substantia nigra neurons encode unexpected financial rewards

The brain's sensitivity to unexpected outcomes plays a fundamental role in an\ud organism's ability to adapt and learn new behaviors. Emerging research suggests that\ud midbrain dopaminergic neurons encode these unexpected outcomes. We used\ud microelectrode recordings during deep brain stimulation surgery to study neuronal activity in\ud the human substantia nigra (SN) while patients with Parkinson's disease engaged in a\ud probabilistic learning task motivated by virtual financial rewards. Based on a model of the ..

Polymeric Particulates to Improve Oral Bioavailability of Peptide Drugs

Oral administration remains the most convenient way of delivering drugs. Recent advances in biotechnology have produced highly potent new molecules such as peptides, proteins and nucleic acids. Due to their sensitivity to chemical and enzymatic hydrolysis as well as a poor cellular uptake, their oral bioavailability remains very low. Despite sophisticated new delivery systems, the development of a satisfactory oral formulation remains a challenge. Among the possible strategies to improve the absorption of drugs, micro- and nanoparticles represent an exciting approach to enhance the uptake and transport of orally administered molecules. Increasing attention has been paid to their potential use as carriers for peptide drugs for oral administration. This article reviews the most common manufacturing methods for polymeric particles and the physiology of particle absorption from the gastrointestinal (GI) tract. In a second part, the use of polymeric particulate systems to improve the oral absorption of insulin is discussed

¿Es la cartera de servicios un instrumento útil para la asignación de recursos farmacéuticos en atención primaria?

ObjetivoConocer si en ciertos equipos de atención primaria ha existido asociación entre el grado de cobertura en determinados servicios y el gasto en fármacos para las patologías incluidas en ellos.DiseñoEstudio descriptivo, retrospectivo.EmplazamientoAtención primaria. INSALUD. Área 1, Huesca.Mediciones y resultados principalesUsando los datos de coberturas de cartera de servicios de 1999 y de gasto en farmacia por subgrupos terapéuticos durante el período enero-octubre del mismo año se analizó:–El servicio de atención a pacientes crónicos: hipercolesterolemia, y se comparó con el gasto en el subgrupo B04A (hipolipemiantes/antiateromatosos).–El servicio de atención a pacientes crónicos: diabetes, y se comparó con el gasto en los subgrupos A10A (insulinas) y A10B (antidiabéticos orales).El gasto se expresó como gasto ajustado por 100 asegurados, usando para el ajuste los coeficientes del INSALUD (coeficiente activos, 0,732; coeficiente pensionistas, 0,268).La relación entre ambas variables se representó gráficamente por una nube de puntos.La existencia de asociación entre ellas se midió utilizando el coeficiente de correlación de Pearson.No se ha encontrado asociación estadísticamente significativa entre el resultado en coberturas y el gasto en farmacia en estos subgrupos.Hipercolesterolemia/hipolipemiantescoeficiente de Pearson, 0,334; IC del 95%, −0,115 a 0,669.Diabetes/antidiabéticos orales e insulinacoeficiente de Pearson < 0,1.ConclusionesExtraemos dos conclusiones:–Las diferencias en coberturas de los servicios analizados no tienen relación directa con el gasto en fármacos.–La cartera de servicios no resulta un buen método en la asignación de recursos para el consumo de fármacos.ObjectiveTo find whether in certain primary care teams an association exists between the level of coverage in determined services and expenditure on drugs for pathologies included in these services.DesignRetrospective descriptive study.SettingPrimary care, INSALUD, Area 1, Huesca.Measurements and main resultsUsing the data on coverage of the service portfolio in 1999 and pharmacy expenditure by therapeutic sub-groups during January-October of the same year, the following was analysed:–The service caring for chronic patients: Hypercholesterolaemia and comparison with expenditure in sub-group B04A (lipid-lowerers/ anti-atheroma drugs).–The service caring for chronic patients: Diabetes and comparison with expenditure in sub-groups A10A (insulin) and A10B (oral antidiabetic drugs).Expenditure was expressed as cost adjusted per 100 insured persons, using the INSALUD coefficients for the adjustment (active person coefficient: 0.732; pensioner coefficient: 0.268). The relationship between the two variables was represented graphically by a cloud of dots. Association between them was measured by Pearson's correlation coefficient. No statistically significant correlation was found between coverage and pharmacy expenditure in these sub-groups. Hypercholesterolaemia/lipidlowerers: Pearson's coefficient=0.334, 95% CI (−0.115 to 0.669). Diabetes/oral diabetic drugs and insulin: Pearson's coefficient < 0.1.ConclusionsThe differences in coverage of the services analysed bear no direct relationship to pharmacy expenditure. The portfolio of services is not a good method of allocation of pharmaceutical resources

Ribonucleotides and manganese ions improve non-homologous end joining by human Polμ

Human DNA polymerase mu (Polμ), a family X member involved in DNA repair, has both template-directed and terminal transferase (template-independent) activities. In addition to their ability to incorporate untemplated nucleotides, another similarity between Polµ and terminal deoxynucleotidyl transferase (TdT) is their promiscuity in using ribonucleotides (NTPs), whose physiological significance is presently unknown. As shown here, Polµ can use NTPs instead of deoxynucleotides (dNTPs) during non-homologous end joining (NHEJ) of non-complementary ends, a Polµ-specific task. Moreover, a physiological concentration of Mn 2+ ions did benefit Polµ-mediated NHEJ by improving the efficiency and accuracy of nucleotide insertion. Analysis of different mutations in the ‘steric gate’ of the active site indicated that Polµ is taking advantage of an open active site, valid for selecting alternative activating metal ions and nucleotides as substrates. This versatility would allow ad hoc selection of the most appropriate nucleotide/metal ion combination for individual NHEJ events to gain efficiency without a cost in terms of fidelity, thus widening the spectrum of available solutions to position a discontinuous template strand in proper register for connection

Experimental and theoretical cross sections for positron scattering from the pentane isomers

10 págs.; 8 figs.; 3 tabs.Isomerism is ubiquitous in chemistry, physics, and biology. In atomic and molecular physics, in particular, isomer effects are well known in electron-impact phenomena; however, very little is known for positron collisions. Here we report on a set of experimental and theoretical cross sections for low-energy positron scattering from the three structural isomers of pentane: normal-pentane, isopentane, and neopentane. Total cross sections for positron scattering from normal-pentane and isopentane were measured at the University of Trento at incident energies between 0.1 and 50 eV. Calculations of the total cross sections, integral cross sections for elastic scattering, positronium formation, and electronic excitations plus direct ionization, as well as elastic differential cross sections were computed for all three isomers between 1 and 1000 eV using the independent atom model with screening corrected additivity rule. No definitive evidence of a significant isomer effect in positron scattering from the pentane isomers appears to be present. ©2016 AIP Publishing LLCG.G. and F.B. would like to acknowledge the Spanish Ministerio de Economía y Productividad (Project No. FIS2012-31230) and the European Science Foundation (COST Action Grants Nos. MP1002–Nano-IBCT and MC1301-CELINA) for financial support. Finally, L.C. thanks the Japan Society for the Promotion of Science for his fellowship.Peer Reviewe

La apuesta por la excelencia en la formación práctica universitaria de futuros profesores

Las revisiones de las aportaciones científicas que se hacen a las reuniones y encuentros sobre la formación inicial del docente, en general, y sobre el prácticum, de un modo más particular, dan a conocer el enorme interés científico que este componente formativo despierta entre los investigadores y proporcionan una idea del volumen de la producción en este foco de indagación científica. El presente trabajo pretende ser una contribución en esta dirección, perfilando, primero, las principales áreas temáticas en las que se han centrado los estudios sobre el prácticum y desgranando, después, indicadores clave garantes de un prácticum de calidad

Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems

Current treatments for Parkinson’s disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly-targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients

Optimization of topical cidofovir penetration using microparticles.

Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol® and Precirol® lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween® 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p < 0.01) 14 days after the beginning of the treatment. Our results showed that Tween® 80 coated Compritol® and Precirol® LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo

Quantitative determination of the antitumor alkyl ether phospholipid edelfosine by reversed-phase liquid chromatography-electrospray mass spectrometry: application to cell uptake studies and characterization of drug delivery systems.

Edelfosine is a synthetic alkyl ether phospholipid that represents a promising class of antitumor agents. However, analytical methods to measure these type compounds are scarce. The lack of a reliable methodology to quantify edelfosine is a major problem in ongoing and scheduled preclinical and clinical trials with this drug. We evaluated the applicability of high-performance liquid chromatography–mass spectrometry to determine edelfosine in biological samples and polymeric delivery systems. Sample pre-treatment involved polymer precipitation or cell lysis with methanol. HPLC separation was performed on an Alltima RPC18 narrow-bore column and edelfosine quantification was done by electrospray ionization mass spectrometry (ESI-MS) using positive ion mode and selected ion monitoring. Assays were linear in the tested range of 0.3–10 μg/ml. The limit of quantification was 0.3 ng/sample in both matrices, namely biological samples and polymeric delivery systems. The interassay precision ranging from 0.79 to 1.49%, with relative errors of −6.7 and 12.8%. Mean extraction recovery was 95.6%. HPLC–ESI-MS is a reliable system for edelfosine analysis and quantification in samples from different sources, combining advantages of full automation (rapidity, ease of use, no need of extensive extraction procedures) with high analytical performance and throughput