Diseño y Desarrollo de Nuevas Entidades Químicas de Interés Farmacéutico. Design and Development of New Chemical Entities of Pharmaceutical Interest.

Este proyecto de investigación se basa fundamentalmente en diversas actividades concernientes a la investigación y desarrollo de nuevos fármacos. Estos estudios se llevan a cabo sobre nuevos derivados de las siguientes drogas líderes utilizadas en el tratamiento del SIDA: zidovudina (AZT), lamivudina (3TC), didanosina (ddI) y un tipo particular de Inhibidores No Nucleosídicos de la Transcriptasa Reversa (INNTR) conocidos como "diarilpirimidinas" (DAPYs). Se plantean para el presente proyecto los siguientes objetivos específicos:1. Diseño racional y síntesis de nuevos compuestos,2. Evaluación de actividades biológicas y citotoxicidad,3. Estudio de las propiedades fisicoquímicas de interés biológico y farmacéutico,4. Estudios farmacocinéticos y biofarmacéuticos.De esta manera, se ha considerado un estudio integrador, tendiente a conocer y entender el posible comportamiento en el organismo de nuevas entidades químicas de interés farmacéutico (NEQF). Así, nuestra hipótesis de trabajo se sustenta en que la variación de las propiedades fisicoquímicas y farmacocinéticas de las drogas actualmente en uso o en etapas de experimentación, podrá incidir favorablemente en la farmacoterapia del SIDA.Cabe destacar que la aplicación de diversos métodos computacionales, constituye una herramienta muy importante que se utilizada para cada uno de los objetivos planteados ya que brinda información complementaria y una ayuda invalorable para el diseño racional de drogas.Así, se diseñarán, prepararán y caracterizarán NEQF, estudiando en detalle sus propiedades moleculares. Se espera que la información generada represente una contribución para el desarrollo de nuevas opciones terapéuticas efectivas frente al agente causativo del SIDA, enfermedad para la cuál la opción de una terapia efectiva está lejos de ser la ideal.Como el proyecto se desarrolla dentro de un ámbito académico, las actividades previstas permitirán a los becarios y tesistas: 1) ampliar y profundizar los conocimientos teóricos relacionados con los temas de estudio; 2) desarrollar su capacidad creativa; 3) posibilitar el trabajo multidisciplinario. Es decir, se formarán recursos humanos altamente capacitados en el diseño y desarrollo de NEQF, finalizando las tesis doctorales en ejecución e incorporando nuevos jóvenes farmacéuticos.A partir de los resultados que se logren en el campo científico y académico, se espera contribuir a la promoción del conocimiento en el área del diseño y del desarrollo de Compuestos Farmacéuticos Activos. Es de nuestro especial interés que los resultados lleven a un posicionamiento del grupo en el área de la Química Medicinal, de la Bioorgánica y de la Biofarmacia.Con relación a la importancia del proyecto, cabe destacar que la Química Medicinal es una disciplina poco desarrollada en nuestro país, por lo tanto contribuirá no sólo a la generación de conocimiento en el área, sino también a la formación de recursos humanos. Cabe destacar la participación de jóvenes farmacéuticos que son los beneficiarios de dicho proceso de formación. Por otra parte, el desarrollo de NEQF conlleva en sí mismo un impacto social y económico importante, y redunda en beneficio de la salud de la población. Teniendo en cuenta la realidad actual, y considerando que la solución final para el tratamiento del SIDA aún no se ha alcanzado, optimizar la actividad/efectividad de fármacos conocidos y estudiar nuevas moléculas que actúen sobre diversas dianas biológicas constituye una esperanza para el tratamiento eficaz de esta enfermedad. Finalmente, teniendo en cuenta que la finalidad del proyecto es desarrollar nuevos agentes anti VIH con potencial aplicación clínica, es de esperar poder interaccionar con la industria farmacéutica y transferir los resultados a la misma.

Electroquímica de sustancias de interés en los sistemas agroalimentario y de sanidad animal. Desarrollo de biosensores electroquímicos. Aplicaciones analíticas.Electrochemistry of substances of interest in agroalimentary and animal health systems. Development of electrochemical biosensors. Analytical applications.

Se estudiarán los mecanismos de reacción electroquímica de las micotoxinas (metabolitos tóxicos generados por hongos) citrinina (CIT), patulina (PAT) y moniliformina (MON), de los antioxidantes naturales alfa, beta, gama y delta tocoferoles, de los flavonoides fisetina (FIS), morina (MOR), luteolina (LUT), rutina (RUT), buteina (BUT), naringenina (NAR) y miricetina (MIR) y de las hormonas esteroides estradiol (EDIOL), estrona (EONA) y estriol (ETRIOL). Por otra parte, se implementarán técnicas electroanalíticas para la detección y cuantificación de estos sustratos en muestras de matrices naturales que los contengan. Se realizará el diseño y caracterización de biosensores enzimáticos a partir de peroxidasas y/o fosfatasa alcalina para la determinación de la micotoxina CIT y de los flavonoides y, por otro, de inmunosensores para las micotoxinas ocratoxina A (OTA) y PAT y hormonas. Para el anclaje de enzimas y/o anticuerpos, se estudiarán las propiedades de electrodos modificados por monocapas autoensambladas, nanotubos de carbono y partículas magnéticas. Se usarán las técnicas de voltamperometría cíclica, de onda cuadrada y de redisolución con acumulación adsortiva, espectroscopías de impedancia electroquímica, electrólisis a potencial controlado, uv-vis e IR, microbalanza de cristal de cuarzo y microscopías de alta resolución (SEM, TEM, AFM). La importancia de este proyecto apunta a la obtención de nuevos datos electroquímicos de los sustratos indicados y conocimientos relacionados con la aplicación de electrodos modificados en la preparación de biosensores y en el desarrollo de técnicas alternativas para la determinación de los analitos mencionados precedentemente. Electrochemical reaction mechanisms of mycotoxins (toxic metabolites generated by fungi) citrinin (CIT), Patulin (PAT) and moniliformin (MON), natural antioxidants alpha, beta, gamma and delta tocopherols, flavonoids fisetin (FIS), morin (MOR), luteolin (LUT), rutin (RUT), butein (BUT), naringenin (NAR), miricetin (MIR) and steroid hormones estradiol (EDIOL), estrone (EONA) and estriole (ETRIOL) will be explored. On the other hand, electroanalytical techniques for the detection and quantification of these substrates in samples of natural matrices will be implemented. The design and characterization of enzymatic biosensors from peroxidases and/or from alkaline phosphatase for the determination of CIT and flavonoids, and also of inmunosensors for ochratoxin A (OTA) and PAT and hormones will be performed. For the anchor of enzymes and/or antibody, properties of electrodes modified by self assembled monolayers, carbon nanotubes and magnetic particles will be explored. Cyclic, square wave and adsorptive stripping voltammetries, electrochemical impedance spectroscopy, controlled potential electrolysis, uv-vis and IR, quartz crystal microbalance and high-resolution microcopies (SEM, TEM, AFM) will be used. The importance of this project is aimed at obtaining new electrochemical data for the indicated substrates and knowledge on the application of modified electrodes in preparation of biosensors and in the development of alternative techniques for the determination of the above-mentioned analytes.

A comparative study of the physical, chemical and microbiological status of soils, as influenced by conventional and reduced tillage

Historically, shifts to reduced and no-tillage management for production of crops were fostered by needs to decrease soil erosion and loss of organic matter, reduce fuel and labour costs and conserve soil water, as compared with conventional fallow tillage management. Recent interest in maintaining soil quality has been stimulated by a renewed awareness of the importance of soil condition to both the sustainability of agricultural production systems and environmental quality (Doran and Parkin, 1996). The aim of this project was to determine the impact on the physical, chemical and microbiological status of the soil of conventional and reduced tillage. It has been suggested that the reduced soil disturbance associated with the tine cultivator improves soil structure, increases nutrient content in the top 10cm of soil, increases microbial activity and improves physical characteristics. From this study it was determined that the environmental benefits linked to reduced tillage in literature, did not develop in the first two years of this programmes implementation. The results of this study determined that soil nutrients did not increase in concentration in the top 10 cm of soil under reduced cultivation. The only exception was exchangeable potassium. As potassium is not a mobile nutrient its movement is dependent on soil disturbance, therefore under reduced cultivation its concentration was allowed to accumulate in the upper horizon of the soil profile. Microbial activity was greater in the conventionally tilled treatments, as determined by total aerobic bacterial numbers. This could be due to the increased rates of soil aeration in this treatment. Numbers of aerobic bacteria were greater in the conventional tillage treatments at both incubation temperatures of 22 and 32° C. The physical characteristics of the soil determined, indicate that below the depth of soil cultivation, cone penetration resistance increases. Therefore the reduced cultivation treatments would be more prone to soil compaction, higher in the soil profile.

Cardiac Surgery Costs According to the Preoperative Risk in the Brazilian Public Health System

AbstractBackground:Heart surgery has developed with increasing patient complexity.Objective:To assess the use of resources and real costs stratified by risk factors of patients submitted to surgical cardiac procedures and to compare them with the values reimbursed by the Brazilian Unified Health System (SUS).Method:All cardiac surgery procedures performed between January and July 2013 in a tertiary referral center were analyzed. Demographic and clinical data allowed the calculation of the value reimbursed by the Brazilian SUS. Patients were stratified as low, intermediate and high-risk categories according to the EuroSCORE. Clinical outcomes, use of resources and costs (real costs versus SUS) were compared between established risk groups.Results:Postoperative mortality rates of low, intermediate and high-risk EuroSCORE risk strata showed a significant linear positive correlation (EuroSCORE: 3.8%, 10%, and 25%; p < 0.0001), as well as occurrence of any postoperative complication EuroSCORE: 13.7%, 20.7%, and 30.8%, respectively; p = 0.006). Accordingly, length-of-stay increased from 20.9 days to 24.8 and 29.2 days (p < 0.001). The real cost was parallel to increased resource use according to EuroSCORE risk strata (R$ 27.116,00 ± R$ 13.928,00 versus R$ 34.854,00 ± R$ 27.814,00 versus R$ 43.234,00 ± R$ 26.009,00, respectively; p < 0.001). SUS reimbursement also increased (R$ 14.306,00 ± R$ 4.571,00 versus R$ 16.217,00 ± R$ 7.298,00 versus R$ 19.548,00 ± R$935,00; p < 0.001). However, as the EuroSCORE increased, there was significant difference (p < 0.0001) between the real cost increasing slope and the SUS reimbursement elevation per EuroSCORE risk strata.Conclusion:Higher EuroSCORE was related to higher postoperative mortality, complications, length of stay, and costs. Although SUS reimbursement increased according to risk, it was not proportional to real costs.

Acute Coronary Syndrome Treatment Costs from the Perspective of the Supplementary Health System

AbstractBackground:Acute coronary syndrome (ACS) is defined as a “group of clinical symptoms compatible with acute myocardial ischemia”, representing the leading cause of death worldwide, with a high clinical and financial impact. In this sense, the development of economic studies assessing the costs related to the treatment of ACS should be considered.Objective:To evaluate costs and length of hospital stay between groups of patients treated for ACS undergoing angioplasty with or without stent implantation (stent+ / stent-), coronary artery bypass surgery (CABG) and treated only clinically (Clinical) from the perspective of the Brazilian Supplementary Health System (SHS).Methods:A retrospective analysis of medical claims of beneficiaries of health plans was performed considering hospitalization costs and length of hospital stay for management of patients undergoing different types of treatment for ACS, between Jan/2010 and Jun/2012.Results:The average costs per patient were R$ 18,261.77, R$ 30,611.07, R$ 37,454.94 and R$ 40,883.37 in the following groups: Clinical, stent-, stent+ and CABG, respectively. The average costs per day of hospitalization were R$ 1,987.03, R$ 4,024.72, R$ 6,033.40 and R$ 2,663.82, respectively. The average results for length of stay were 9.19 days, 7.61 days, 6.19 days and 15.20 days in these same groups. The differences were significant between all groups except Clinical and stent- and between stent + and CABG groups for cost analysis.Conclusion:Hospitalization costs of SCA are high in the Brazilian SHS, being significantly higher when interventional procedures are required.

Verkehrswertermittlung von Industrieimmobilien unter besonderer Betrachtung des Bodenwertes

Setting: There exists very little supportive valuation literature for the valuation of industrial properties and the present state of research is capable of improvement. Objective: A critical examination of the procedure for the determination of the market value of industrial properties in accordance with § 194 Building Code will be made on the basis of the relevant valuation literature. Based on using standard valuation practices there should be a ground value derived for an industrial estate. Conclusion: When valuing industrial properties economic use is crucial, therefore the income approach is applied in order to attain the market value of the property. Difficulties which may arise include customary approaches for rent, property management costs and interest rates. Based on a Germany-wide cross-comparison with other automobile-producing properties a plausible range for the derivation of the groundvalue was determined. At the time of submission, the determination of the ground value by the expert Committee was unfinished.

Old Akkadian inscriptions in Chicago Natural History Museum; texts of legal and business interest / Ignace J. Gelb, Professor of Assyriology, The Oriential Institute, The University of Chicago.

v.44:no.2(1955)

Illustrations of British mycology, containing figures and descriptions of the funguses of interest and novelty indigenous to Britain. By Mrs. T.J. Hussey ...

ser. 2

Illustrations of British mycology, containing figures and descriptions of the funguses of interest and novelty indigenous to Britain. By Mrs. T.J. Hussey ...

ser. 1

The optimal behaviour of firms facing stochastic costs

This paper aims at assessing the optimal behavior of a firm facing stochastic costs of production. In an imperfectly competitive setting, we evaluate to what extent a firm may decide to locate part of its production in other markets different from which it is actually settled. This decision is taken in a stochastic environment. Portfolio theory is used to derive the optimal solution for the intertemporal profit maximization problem. In such a framework, splitting production between different locations may be optimal when a firm is able to charge different prices in the different local markets.

Interest rate determination in the interbank market

The purpose of this paper is to study the determinants of equilibrium in the market for daily funds. We use the EONIA panel database which includes daily information on the lending rates applied by contributing commercial banks. The data clearly shows an increase in both the time series volatility and the cross section dispersion of rates towards the end of the reserve maintenance period. These increases are highly correlated. With respect to quantities, we find that the volume of trade as well as the use of the standing facilities are also larger at the end of the maintenance period. Our theoretical model shows how the operational framework of monetary policy causes a reduction in the elasticity of the supply of funds by banks throughout the reserve maintenance period. This reduction in the elasticity together with market segmentation and heterogeneity are able to generate distributions for the interest rates and quantities traded with the same properties as in the data.

Credit markets and the propagation of monetary policy shocks

This paper analyzes the propagation of monetary policy shocks through the creation of credit in an economy. Models of the monetary transmission mechanism typically feature responses which last for a few quarters contrary to what the empirical evidence suggests. To propagate the impact of monetary shocks over time, these models introduce adjustment costs by which agents find it optimal to change their decisions slowly. This paper presents another explanation that does not rely on any sort of adjustment costs or stickiness. In our economy, agents own assets and make occupational choices. Banks intermediate between agents demanding and supplying assets. Our interpretation is based on the way banks create credit and how the monetary authority affects the process of financial intermediation through its monetary policy. As the central bank lowers the interest rate by buying government bonds in exchange for reserves, high productive entrepreneurs are able to borrow more resources from low productivity agents. We show that this movement of capital among agents sets in motion a response of the economy that resembles an expansionary phase of the cycle.

Search and bargaining in large markets with homogeneous traders

We study pair-wise decentralized trade in dynamic markets with homogeneous, non-atomic, buyers and sellers that wish to exchange one unit. Pairs of traders are randomly matched and bargaining a price under rules that offer the freedom to quit the match at any time. Market equilbria, prices and trades over time, are characterized. The asymptotic behavior of prices and trades as frictions (search costs and impatience) vanish, and the conditions for (non) convergence to walrasian prices are explored. As a side product of independent interest, we present a self-contained theory of non-cooperative bargaining with two-sided, time-varying, outside options.