Manejo farmacoterapéutico del paciente hospitalizado con enfermedad de Parkinson

236 p.

Diseño de un vector no viral basado en nanopartículas lipídicas para el tratamiento de la hepatitis C mediante ARN de interferencia

199 p.

Obtenção de álcool alílico (PROP-2-EN-1-OL) a partir da glicerina derivada do biodiesel de óleo de mamona

In this work, biodiesel was produced from castor oil that was a byproduct glycerin. The molar ratio between oil and alcohol, as well as the use of (KOH) catalyst to provide the chemical reaction is based on literature. The best results were obtained using 1 mol of castor oil (260g) to 3 moles of methyl alcohol (138g), using 1.0% KOH as catalyst at a temperature of 260 ° C and shaken at 120 rpm. The oil used was commercially available, the process involves the reaction of transesterification of a vegetable oil with methyl alcohol. The product of this reaction is an ester, biodiesel being the main product and the glycerin by-product which has undergone treatment for use as raw material for the production of allyl alcohol. The great advantage of the use of glycerin to obtain allyl alcohol is that its use eliminates the large amount of waste of the biodiesel and various forms of insult to the environment. The reactions for the formation of allyl alcohol was conducted from formic acid and glycerin in a ratio 1/1, at a temperature of 260oC in a heater blanket, being sprayed by a spiral condenser for a period of 2 hours and the product obtained contains mostly the allylic alcohol .. The monitoring of reactions was performed by UV-Visible Spectrophotometer: FTIR Fourier transform, the analysis showed that these changes occur spectrometer indicating the formation of the product allylic alcohol (prop-2-en-1-ol) in the presence of water, This alcohol was appointed Alcohol GL. The absorption bands confirms that the reaction was observed in (υ C = C) 1470 -1600 cm -1 and (υ CO), 3610-3670 attributed to C = C groups and OH respectively. The thermal analysis was carried out in a thermogravimetric analyzer SDT Q600, where the mass and temperature are displayed against time, that allows checking the approximate rate of heating. The innovative methodology developed in the laboratory (LABTAM, UFRN), was able to treat the glycerine produced by transesterification of castor oil and used as raw material for production of allyl alcohol, with a yield of 80%, of alcohol, the same is of great importance in the manufacture of polymers, pharmaceuticals, organic compounds, herbicides, pesticides and other chemicals

Efeito dos nutrientes (nitrogênio e fósforo) sobre o desenvolvimento da Gracilaria birdiae: crescimento e possível uso como biofiltro

Marine shrimp farming has grown exponentially during the last years in Brazil. In spite of the promising economical situation, this activity is facing an increasing criticism due to its environmental impact. Thus, the necessity of alternatives to mitigate environmental degradation caused by this activity. An alternative that is being studied is the policulture that is the integrated culture of two or more organisms, normally one of them a filtering organism. Among filtering organisms, macroalgae are very practicable because they are efficient in the removal of the exceeding nutrients of the water and do not leave residues in the water. Besides, the integrated culture with macroalgae allows the economical exploration of the seaweed (for the manufacture of jelly and jam, for the dairy industry, pharmaceuticals, etc.) along with possibility of a sustainable aquaculture. In the present experiment, the development of the seaweed Gracilaria birdiae, the influence and tolerance of this species to the environmental parameters, and its absorption efficiency in relation with the three kinds of macronutrients (NH4+, NO3- and PO4-3) found in the effluents of marine shrimp farming was studied. The experiment was divided in two parts: a laboratorial part and one part carried under natural conditions. The water used in the laboratory trial was collected in the shrimp ponds of Tecnarão farm and distributed in aquaria containing 20 g of G. birdiae. In the field trial, 0.5 kg of G. birdiae was inserted in PVC cages cultivated in the farm. The results of the study showed a modest growth of G. birdiae, probably due to its low tolerance to highly eutrophicated environments. However, the removal of nutrients was very expressive. Ammonia was reduced in approximately 34 %. Ortho-phosphate showed a reduction of 93.5 %. The capacity of biofiltration of the NO3- by the macro algae was of 100 %, showing that G. birdiae is a seaweed-filtered with a high level of removal for this nutrient under laboratorial conditions. In spite of the low growth of the macro algae in the experiment, the results in relation to the removal of nutrients of the water was encouraging, suggesting that this species can be an efficient biofilter and thus, a strong candidate to be used in a sustainable aquaculture

Avaliação ecotoxicológica de fármacos psicotrópicos e suas possíveis interações com nanomateriais usando embriões de peixe-zebra

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2016.

Assessment of the Occurrence and Potential Risks of Antibiotics and their Metabolites in South Florida Waters Using Liquid Chromatography Tandem Mass Spectrometry

An automated on-line SPE-LC-MS/MS method was developed for the quantitation of multiple classes of antibiotics in environmental waters. High sensitivity in the low ng/L range was accomplished by using large volume injections with 10-mL of sample. Positive confirmation of analytes was achieved using two selected reaction monitoring (SRM) transitions per antibiotic and quantitation was performed using an internal standard approach. Samples were extracted using online solid phase extraction, then using column switching technique; extracted samples were immediately passed through liquid chromatography and analyzed by tandem mass spectrometry. The total run time per each sample was 20 min. The statistically calculated method detection limits for various environmental samples were between 1.2 and 63 ng/L. Furthermore, the method was validated in terms of precision, accuracy and linearity. The developed analytical methodology was used to measure the occurrence of antibiotics in reclaimed waters (n=56), surface waters (n=53), ground waters (n=8) and drinking waters (n=54) collected from different parts of South Florida. In reclaimed waters, the most frequently detected antibiotics were nalidixic acid, erythromycin, clarithromycin, azithromycin trimethoprim, sulfamethoxazole and ofloxacin (19.3-604.9 ng/L). Detection of antibiotics in reclaimed waters indicates that they can’t be completely removed by conventional wastewater treatment process. Furthermore, the average mass loads of antibiotics released into the local environment through reclaimed water were estimated as 0.248 Kg/day. Among the surface waters samples, Miami River (reaching up to 580 ng/L) and Black Creek canal (up to 124 ng/L) showed highest concentrations of antibiotics. No traces of antibiotics were found in ground waters. On the other hand, erythromycin (monitored as anhydro erythromycin) was detected in 82% of the drinking water samples (n.d-66 ng/L). The developed approach is suitable for both research and monitoring applications. Major metabolites of antibiotics in reclaimed wates were identified and quantified using high resolution benchtop Q-Exactive orbitrap mass spectrometer. A phase I metabolite of erythromycin was tentatively identified in full scan based on accurate mass measurement. Using extracted ion chromatogram (XIC), high resolution data-dependent MS/MS spectra and metabolic profiling software the metabolite was identified as desmethyl anhydro erythromycin with molecular formula C36H63NO12 and m/z 702.4423. The molar concentration of the metabolite to erythromycin was in the order of 13 %. To my knowledge, this is the first known report on this metabolite in reclaimed water. Another compound acetyl-sulfamethoxazole, a phase II metabolite of sulfamethoxazole was also identified in reclaimed water and mole fraction of the metabolite represent 36 %, of the cumulative sulfamethoxazole concentration. The results were illustrating the importance to include metabolites also in the routine analysis to obtain a mass balance for better understanding of the occurrence, fate and distribution of antibiotics in the environment. Finally, all the antibiotics detected in reclaimed and surface waters were investigated to assess the potential risk to the aquatic organisms. The surface water antibiotic concentrations that represented the real time exposure conditions revealed that the macrolide antibiotics, erythromycin, clarithromycin and tylosin along with quinolone antibiotic, ciprofloxacin were suspected to induce high toxicity to aquatic biota. Preliminary results showing that, among the antibiotic groups tested, macrolides posed the highest ecological threat, and therefore, they may need to be further evaluated with, long-term exposure studies considering bioaccumulation factors and more number of species selected. Overall, the occurrence of antibiotics in aquatic environment is posing an ecological health concern.

Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens

The aim is tassess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%). A 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily (‘condensed’ regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily (‘conservative’ regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naïve patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in (‘condensed’ vs. ‘conservative’) 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for ‘condensed’ vs. ‘conservative’; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/‘condensed’ vs. high-dose/‘conservative’ and 84.9% vs. 73.6% (P = 0.030) for low-dose/‘conservative’ vs. low-dose/‘condensed’. Initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group.

Immobilized Microalgae for Nutrient Recovery from Source Separated Urine

Shortages in supply of nutrients and freshwater for a growing human population are critical global issues. Traditional centralized sewage treatment can prevent eutrophication and provide sanitation, but is neither efficient nor sustainable in terms of water and resources. Source separation of household wastes, combined with decentralized resource recovery, presents a novel approach to solve these issues. Urine contains within 1 % of household waste water up to 80 % of the nitrogen (N) and 50 % of the phosphorus (P). Since microalgae are efficient at nutrient uptake, growing these organisms in urine might be a promising technology to concomitantly clean urine and produce valuable biomass containing the major plant nutrients. While state-of-the-art suspension systems for algal cultivation have mayor shortcomings in their application, immobilized cultivation on Porous Substrate Photobioreactors (PSBRs) might be a feasible alternative. The aim of this study was to develop a robust process for nutrient recovery from minimally diluted human urine using microalgae on PSBRs. The green alga Desmodesmus abundans strain CCAC 3496 was chosen for its good growth, after screening 96 algal strains derived from urine-specific isolations and culture collections. Treatment of urine, 1:1 diluted with tap water and without addition of nutrients, was performed at a light intensity of 600 μmol photons m-2 s-1 with 2.5 % CO2 and at pH 6.5. A growth rate of 7.2 g dry weight m-² day-1 and removal efficiencies for N and P of 13.1 % and 94.1 %, respectively, were determined. Pre-treatment of urine with activated carbon was found to eliminate possible detrimental effects of pharmaceuticals. These results provide a basis for further development of the technology at pilot-scale. If found to be safe in terms human and environmental health, the biomass produced from three persons could provide the P for annual production of 31 kg wheat grain and 16 kg soybean, covering the caloric demand in food for almost one month of the year for such a household. In combination with other technologies, PSBRs could thus be applied in a decentralized resource recovery system, contributing to locally close the link between sanitation and food production.

2013 survey of Iowa groundwater and evaluation of public well vulnerability classifications for contaminants of emerging concern (2015)

Studies in Iowa have long documented the vulnerability of wells with less than 50 feet (15 meters) of confining materials above the source aquifer to contamination from nitrate and various pesticides. Recent studies in Wisconsin have documented the occurrence of viruses in untreated groundwater, even in wells considered to have little vulnerability to contamination from near-surface activities. In addition, sensitive methods have become available for analyses of pharmaceuticals and pesticides. This study represents the first comprehensive examination of contaminants of emerging concern in Iowa’s groundwater conducted to date, and one of the first conducted in the United States. Raw groundwater samples were collected from 66 public supply wells during the spring of 2013, when the state was recovering from drought conditions. Samples were analyzed for 206 chemical and biological parameters; including 20 general water-quality parameters and major ions, 19 metals, 5 nutrients, 10 virus groups, 3 species of pathogenic bacteria, 5 microbial indicators, 108 pharmaceuticals, 35 pesticides and pesticide degradates, and tritium. The wells chosen for this study represent a diverse range of ages, depths, confining material thicknesses, pumping rates, and land use settings. The most commonly detected contaminant group was pesticide compounds, which were present in 41% of the samples. As many as 6 pesticide compounds were found together in a sample, most of which were chloroacetanilide degradates. While none of the measured concentrations of pesticide compounds exceeded current benchmark levels, several of these compounds are listed on the U.S. Environmental Protection Agency’s Contaminant Candidate List and could be subject to drinking water standards in the future. Despite heavy use in the past decade, glyphosate was not detected, and its metabolite, aminomethylphosphonic acid, was only detected in two of 60 wells tested (3%) at the detection limit of 0.02 μg/L. Pharmaceutical compounds were detected in 35% of 63 samples. Of the 14 pharmaceuticals detected, six had reported concentrations above the method reporting limit, with the maximum reported concentration of 826 ng/L for acetaminophen. Diphenhydramine was the only pharmaceutical to have two detections above the reporting limit, at 24.5 and 145 ng/L. Eight pharmaceuticals had confirmed detections at concentrations below the method reporting limit. Caffeine was the most frequently detected pharmaceutical compound (25%), followed by the caffeine metabolite, 1,7-dimethylxanthine (16%). Microorganisms were detected in 21% of the wells using quantitative polymerase chain reaction methodologies. The most frequently detected microorganism was the pepper mild mottle virus (PMMV), a plant pathogen found in human waste. PMMV was detected in 17% of samples at concentrations ranging from 0.4 to 6.38 gene copies per liter. GII norovirus, human polyomavirus, bovine polyomavirus, and Campylobacter were also detected, while adenovirus, enterovirus, GI norovirus, swine hepatitis E, Salmonella, and enterohemmorhagic E. coli were not detected. No correlations were found between viruses or pathogenic bacteria and microbial indicators. Wells with less than 50 feet (15 meters) of confining material were shown to have greater incidence of surface-related contaminants; however, significant relationships (p<0.05) between confining layer thickness and contaminants were only found for nitrate and herbicides.

Revisión del uso de los medicamentos biosimilares vs. biológicos: implicaciones para la salud en Colombia.

Este documento tiene como objetivo describir las implicaciones para la salud con el uso de medicamentos biosimilares en comparación con los medicamentos biológicos en Colombia. Así mismo, describir el contexto normativo acerca del uso de medicamentos biosimilares, las recomendaciones y lineamientos sobre seguridad y efectividad del uso de medicamentos Biosimilares y Biológicos, partiendo de sus diferencias biomoleculares. Para esto, se desarrolló una revisión documental electrónica y manual de la literatura en bases de datos, revistas y libros limitada a términos MeSH. La selección de los artículos incluyo documentos completos publicados en revistas indexadas de los últimos 10 años, en español e inglés; la información recolectada se organizó para la construcción del presente documento. Concluyendo, se encontró que las patentes de muchos medicamentos biológicos han vencido o están próximas a caducar y varios biosimilares están desarrollándose y comercializándose incluso en países sin regulaciones estrictas. Los biosimilares nunca podrán ser iguales al original por su complejidad molecular, por ello debemos integrarlos a los sistemas de farmacovigilancia mejorando trazabilidad e identificando su origen mientras se establecen denominaciones comunes distinguibles. La evidencia actual sugiere que la regulación de medicamentos biosimilares debe ser evaluada y armonizada en todo el mundo.

Mercadeo farmacéutico de productos bajo prescripción: efectos de las estrategias Direct-to-Consumer-Advertising en el comportamiento de los consumidores y de prescripción de los médicos

Este proyecto se origina en el interés de analizar las estrategias actuales de promoción de productos farmacéuticos, en el marco del debate sobre el efecto persuasivo o informativo que la publicidad directa tiene sobre los consumidores. El objetivo es determinar el efecto de las estrategias de promoción directa para consumidores (Direct to Consumer Advertising [DTCA]) sobre el comportamiento de compra de pacientes y las prescripciones que formulan los médicos en el mercado de productos bajo receta en Estados Unidos. Para tal fin se propuso realizar una monografía que incluyera una revisión de literatura de carácter argumentativo, consultando información de nivel secundario en bases de datos científicas cuyos contenidos obedecieran a criterios metodológicos determinados por la naturaleza argumentativa del estudio. Adicionalmente, se analizó el debate sobre estos anuncios a la luz de dos estudios realizados a pacientes con cáncer de seno, próstata y colon, liderados por el Pennsylvania Cancer Registry con los productos biofarmacéuticos Avodart® y Flomax®. Finalmente, la investigación se fundamentó en la relación del mercado farmacéutico en Estados Unidos con cada uno de los agentes que interactúan en él; consumidores, médicos prescriptores y empresas farmacéuticas, así como el valor que estos comparten través de dichas interacciones. Se concluye que el comportamiento de compra de los consumidores está determinado por la naturaleza de la patología que padecen y el comportamiento de los profesionales que prescriben a sus pacientes se ve influenciado por los anuncios DTCA.

Remoção de ibuprofeno de águas por oxidação catalítica

A ocorrência e destino de fármacos no ambiente aquático tem vindo a ser reconhecido como um problema emergente em química ambiental. Alguns compostos são resistentes à degradação nas estações de tratamento de águas residuais, ETARs, enquanto que outros, ainda que sofram degradação parcial, continuam a ser lançados nos meios aquáticos em quantidades apreciáveis. O Ibuprofeno, IB, um dos anti­ inflamatórios mais consumidos por todo o mundo, é um dos fármacos mais detectados no meio hídrico. Apesar dos sistemas de tratamento convencionais utilizados nas ETARs removerem até 90% do IB das águas residuais, é frequente o efluente descarregado conter ainda quantidades significativas deste poluente. A presença destes compostos no ambiente deve ser avaliada dado que possuem actividade biológica, mesmo a baixas concentrações. Os processos avançados de oxidação com peróxido de hidrogénio, na presença de catalisadores heterogéneos, permitem melhorar significativamente a remoção deste tipo de compostos em águas. Assim, foi objectivo deste trabalho o estudo da utilização de peróxido de hidrogénio como agente oxidante na remoção de IB em soluções aquosas, na presença de complexo de acetilacetonato de Ni (II) disperso em PDMS ou encapsulado em zeólitos NaY. Para o doseamento do fármaco em solução foi necessário desenvolver um método analítico consistindo de separação cromatográfica por HPLC e detecção e quantificação por UV-Vis. Não houve necessidade de recorrer a um passo de pré­ concentração de amostras por extracção em fase sólida (SPE) devido ao facto das concentrações de IB medidas ao longo do trabalho se terem sempre encontrado acima do LOQ (811 g L-1) do método analítico por injecção directa. Deste estudo pode concluir-se que o catalisador que apresentou melhor actividade catalítica e consequentemente maior remoção do IB em solução, foi o complexo de acetilacetonato de Ni (II), disperso em PDMS. Foi avaliada a influência, na conversão do IB, de diferentes parâmetros como a concentração inicial de peróxido de hidrogénio adicionada, quantidade de catalisador utilizada na mistura reaccional e temperatura. Os resultados permitiram concluir que os aumentos destes parâmetros conduzem a um aumento da actividade catalítica da reacção. A estabilidade catalítica do acetilacetonato de Ni (II)/PDMS, foi avaliada em ensaios consecutivos com a mesma amostra e nas mesmas condições, tendo-se observado que, após 8 utilizações, o catalisador perde ligeiramente a actividade (cerca de 11% do seu valor inicial). ABSTRACT: The presence and fate of pharmaceuticals in the aquatic environment is an emergent issue in environmental chemistry. Some compounds are poorly removed in wastewater treatment plants (WWTPs) while others, in spite of being partially removed, are still present in the WWTPs effluents and discharged in the receiving water bodies. Ibuprofen, IB, a non-steroid anti-inflammatory drug, is one of the most used and also one of the most frequently detected pharmaceutical contaminants in aquifers worldwide. Its removal by conventional wastewater treatment processes used in most WWTPs is usually high (up to 90% of incoming IB may be removed), but duet the high loads present in the influents, still significant amounts of IB usually leave the WWTPs in the treated effluents. The presence of these compounds in the environment must be evaluated considering that they may have some biological activity even at low concentrations. Advanced oxidation processes using hydrogen peroxide, in the presence of heterogeneous catalysts, provide a significantly improved removal of this type of substances from waters. Therefore, it was the aim of this work to study the use of hydrogen peroxide as an oxidizing agent in the removal of IB from aqueous solutions, in the presence of the catalyst nickel (II) acetylacetonate dispersed in PDMS or encapsulated in the NaY zeolite. For the quantification of the pharmaceutical in aqueous solution it was necessary to develop an analytical methodology based in chromatographic separation by HPLC and with UV-Vis detection and quantification. There was no need for a pre­concentration step of the samples by solid phase extraction (SPE) as the IB concentrations measured were always above the limit of quantification (811 bL1 of) the analytical method. The results from this study have shown that the catalyst which presented the best catalytic activity and the highest IB removal in solution was nickel (II) acetylacetonate dispersed in PDMS.

Nanocomposites based on poly(caprolactone)-chitosan electrospun nanofibers and metallic oxide nanoparticles. Their potential use to adsorption and photocatalytic degradation of organic contaminants

Pollution of water bodies is one of the most common environmental problems today. Organic pollutants are one of the main drawbacks in this natural resource, among which the following stand out long-lived dyes, pharmaceuticals, and pesticides. This research aims at obtaining nanocomposites based on polycaprolactone-chitosan (PCL-CS) electrospun nanofibers (NFs) containing TiO2 nanoparticles (NPs) for the adsorption and photocatalytic degradation of organic pollutants, using Rhodamine B as a model. The fabricated hybrid materials were characterized by FT-IR, TGA, DSC, SEM, TEM, tensile properties, and the contact angle of water drops. The photoactivity of the NFs was investigated using a batch-type system by following UV-Vis absorbance and fluorescence of rhodamine B (RhB). For this purpose, TiO2NPs were successfully ex-situ incorporated into the polymer matrix promoting good mechanical properties and higher hydrophilicity of the material. The results showed that CS in the NFs increased the absorption and degradation of RhB by the TiO2NPs. CS attracted the pollutant molecules to the active sites vicinity of TiO2NPs, favoring initial adsorption and degradation. In other words, a bait-hook-and-destroy effect was evidenced. It also was demonstrated that the sensitization of TiO2 by organic dyes (e.g., perylene derivative) considerably improves the photocatalytic activity under visible radiation, allowing the use of low amounts of TiO2. (≈0.05 g/1 g of fiber). Hence, the current study is expected to contribute with an environmentally friendly green alternative solution.