Ionic liquids: A pharmaceutical perspective

In the last decades, ionic liquids (ILs) progressed from chemical curiosities to interesting biological compounds apprehending the attention of researchers of distinct areas, from chemistry to pharmacology. Initially, ILs were explored as materials for diverse applications due to the possibility of synthesize compounds with targeted chemical properties combined with selected physical properties. More recently, the emergence of ILs with biological activity revolutionized the scientific focus of these compounds and opened interesting perspectives regarding their pharmaceutical application. From the pharmaceutical point of view, an IL approach, in the design of novel active pharmaceutical ingredients (APIs), appears to be appropriate as it enables the chemical manipulation of the compounds with specific objectives related with the manufacturing process, the stability of the formulation, bioavailability and eventual adverse effects. Furthermore, even though crystallinity confers advantages during isolation, processing and storage of the drug, it is known that solid forms of APIs often suffer from low solubility and polymorphic conversion which can influence negatively the bioavailability of the drug and ultimately its therapeutic effect. On a distinct perspective, the possibility of engineering the properties of ILs by manipulating anion-cation combinations, in association with their solvent properties and in some cases water-miscibility, are considered promising characteristics regarding the applicability of ILs as solvents or carriers of pharmaceutical drugs. In this chapter it is intended to expose the pharmaceutical potential of ILs through the discussion of their utilization either as APIs or solvents/carriers of pharmaceutical drugs. The discussion will be centered on the benefits of the IL approach for the development of novel drug candidates considering not only physico-chemical aspects but also the pharmaceutical profile of the developed active pharmaceutical ingredients with IL properties. Considering the utilization of ILs as solvents of drugs or as part of drug delivery systems, it is anticipated that the discussion will be focused on the efficiency and toxicity of the systems and on their influence on the pharmacokinetics and pharmacodynamics of the vehiculated drugs. It is also planned to debate the motivations for the pharmaceutical usage of ILs as well as their peculiar properties that launched them in this context. Currently, the pharmaceutical utilization of ILs is one of the most relevant applications of these solvents, with impact on the safety and effectiveness of the involved processes and with benefits in terms of pharmaceutical formulations and pharmacological activity. It is our belief that this chapter is adequate for the book in project and can greatly enhance its acceptance and interest by readers in distinct research areas

Biofilms in drinking water: problems and solutions

The main goal of water companies is to deliver to each consumer microbiologically safe drinking water (DW), adequate in quantity and delivery pressure and acceptable in terms of taste, odour and appearance. Drinking water distribution systems (DWDS) are known to harbour biofilms, even in the continuous presence of a disinfectant. These biofilms are a source of planktonic bacteria, which will remain present when the water is delivered through a consumer’s tap. The presence of biofilms in DWDS constitutes one of the currently recognized hazards affecting the microbiological quality of the product and may lead to a number of unwanted effects on the organoleptic quality of the distributed water. Importantly, biofilms constitute a persistent reservoir of pathogenic microorganisms, which are responsible for several waterborne diseases. Antimicrobial products, particularly chlorine, have been the main weapons used to disinfect DW. Although this strategy is widespread, there are not yet standardized disinfection strategies with reliable efficacy in the control of biofilms. This review covers the advances in the knowledge of public health problems caused by the presence of biofilms in DWDS and the current strategies for DW disinfection and associated biofilms.This work was supported by the Operational Programme for Competitiveness Factors - COMPETE and by FCT - the Portuguese Foundation for Science and Technology through Project Bioresist - PTDC/EBB-EBI/105085/2008 (Manuel Simoes) and the post-doctoral grant SFRH/BPD/81982/2011 (Lucia C. Simoes)

Impacts of the Proposals For Tariff Reductions in Non-Agricultural Market Access (Nama)

O Estudo Visa Avaliar os Impactos de Propostas Alternativas de Redução da Proteção Tarifária de Bens Não-Agrícolas Sobre a Economia Brasileira Usando um Modelo de Equilíbrio Geral Computável. Foram Simulados os Impactos da Implementação de Cortes Tarifários de Acordo com Diferentes Coeficientes para a Fórmula Suíça. as Simulações Foram Realizadas com o Modelo Gtap e Todos os Choques Tarifários Foram Calculados a Partir de Informações da Base de Dados Macmap. Além de Analisar Resultados Macroeconômicos e Setoriais, Também foi Testada a Sensibilidade dos Resultados em Relação ao Aumento das Elasticidades de Armington e À Ocorrência de uma Simultânea Liberalização de Tarifas Sobre Bens Agrícolas.

Coaggregation between bacteria isolated from tap water: role of extracellular polymeric substances production and evidence of a bridging bacteria

Six dominant heterotrophic bacteria isolated from tap water coming from a drinking water distribution system in the North of Portugal were identified by 16S ribosomal DNA gene sequencing. Their coaggregation partnerships were determined immediately after dual bacteria mixture, 24 h and 48 h later, using the visual coaggregation assay. Interspecies interactions were also analysed by scanning electron microscopy (SEM) and epifluorescence microscopy using a DNA binding stain. Extracellular polymeric substances – EPS (proteins and polysaccharides) were assessed along time and correlated with the coaggregation properties. The bacteria isolated were Acinetobacter calcoaceticus, Burkholderia cepacia, Methylobacterium sp., Mycobacterium mucogenicum, Sphingomonas capsulata, Staphilococcus sp. Only A. calcoaceticus coaggregated with all the five other strains. The other bacteria had not the ability to coaggregate in the absence of A. calcoaceticus. Coaggregation after immediate bacteria association was higher for A. calcoaceticus/B. cepacia, being the only interaction that decreased coaggregation score along time (24 h and 48 h later). The other interactions maintained (A. calcoaceticus/Staphilococcus sp.) and increased (A. calcoaceticus/Methylobacterium sp., A. calcoaceticus/M. mucogenicum, A. calcoaceticus/S. capsulata) coaggregation scores along time. Microscopic analysis revealed a higher degree of interaction between species than the one obtained by the visual coaggregation assay. Coaggregation ability was not related with EPS production because the variation along time of the extracellular proteins and polysaccharides content seemed not to account for coaggregation phenomenon. Biofilm formation (single and mixed species) studies using an in vitro microplate assay are under running in order to ascertain the function of A. calcoaceticus as bridging bacteria in biofilm development and to correlate coaggregation results with biofilm formation ability

The effects of metabolite molecules produced by drinking water-isolated bacteria on their single and multispecies biofilms

The elucidation of the mechanisms by which diverse species survive and interact in drinking water (DW) biofilm communities may allow the identification of new biofilm control strategies. The purpose of the present study was to investigate the effects of metabolite molecules produced by bacteria isolated from DW on biofilm formation. Six opportunistic bacteria, viz. Acinetobacter calcoaceticus, Burkholderia cepacia, Methylobacterium sp., Mycobacterium mucogenicum, Sphingomonas capsulata and Staphylococcus sp. isolated from a drinking water distribution systems (DWDS) were used to form single and multispecies biofilms in the presence and absence of crude cell-free supernatants produced by the partner bacteria. Biofilms were characterized in terms of mass and metabolic activity. Additionally, several physiological aspects regulating interspecies interactions (sessile growth rates, antimicrobial activity of cell-free supernatants, and production of iron chelators) were studied to identify bacterial species with biocontrol potential in DWDS. Biofilms of Methylobacterium sp. had the highest growth rate and M. mucogenicum biofilms the lowest. Only B. cepacia was able to produce extracellular iron-chelating molecules. A. calcoaceticus, B. cepacia, Methylobacterium sp. and M. mucogenicum biofilms were strongly inhibited by crude cell-free supernatants from the other bacteria. The crude cell-free supernatants of M. mucogenicum and S. capsulata demonstrated a high potential for inhibiting the growth of counterpart biofilms. Multispecies biofilm formation was strongly inhibited in the absence of A. calcoaceticus. Only crude cell-free supernatants produced by B. cepacia and A. calcoaceticus had no inhibitory effects on multispecies biofilm formation, while metabolite molecules of M. mucogenicum showed the most significant biocontrol potential.The authors acknowledge the financial support provided by the Portuguese Foundation for Science and Technology (SFRH/BD/31661/2006 - Lucia C. Simoes)

Intergeneric coaggregation among drinking water bacteria: evidence of a role for acinetobacter calcoaceticus as a bridging bacterium

Intergeneric coaggregation of drinking water bacteria was tested. Acinetobacter calcoaceticus was found not only to autoaggregate but also to coaggregate with four of the five other isolates (Burkholderia cepacia, Methylobacterium sp., Mycobacterium mucogenicum, Sphingomonas capsulata, and Staphylococcus sp.). In its absence, no coaggregation was found. Interactions were lectin-saccharide mediated. The putative bridging function of A. calcoaceticus was evidenced by multispecies biofilm studies, through a strain exclusion process.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/31661/2006; SFRH/BPD/20582/2004

Adhesion potential of bacteria isolated from tap water to several materials using a modified microtiter-plate test

Autochthonous heterotrophic aerobic bacteria from drinking water were isolated, identified by growth on selective media, biochemical tests and 16S rDNA gene sequence. From 25 different isolated bacteria, 8 representative bacteria were selected in order to test their adhesion ability to four different support materials. The bacteria selected were Acinetobacter calcoaceticus, Burkholderia cepacia, Methylobacterium sp., Mycobacterium mucogenicum, Sphingomonas capsulata, Staphylococcus sp., Stenotrophomonas maltophilia and the materials used for adhesion were stainless steel ASI 316 (SS), polyethylene (PE), polyvinyl chloride (PVC) and polystyrene (PS). Strain variation on adherence ability was assessed by using two distinct strains of Sph. capsulata (sp. 1 and sp. 2) and S. maltophilia (sp.1 and sp. 2). The adhesion assays were performed during 2 h using a modified microtiter-plate test. The results obtained revealed that the bacteria adhered in a higher extent to PE (P < 0.05), with the exception of Methylobacterium sp. (higher colonization of SS) and Staphylococcus sp. (higher colonization of PS). Strong and moderate adherence were detected for A. calcoacticus and Staphylococcus sp. - adhered to the four materials used, while only Sph. capsulata sp. 1 was non-adherent to the tested materials. Furthermore, it is expected that some of the strong and moderately (A. calcoaceticus, Staphylococcus sp. and S. maltophilia sp. 1) adherent bacteria will play a determinant role in the primary colonization of the surfaces. The use of distinct S. maltophilia and Sph. capsulata strains showed the existence of varying ability of adherence for the distinct strains, demonstrating that no strain can effectively represent its species. This study provides information about a rapid and reliable methodology for bacteria adherence ability assessment and gives useful clues about the behaviour of drinking water autochthonous bacteria when exposed to potential adhesion surfaces.European Commission Research Project SAFER; Portuguese Foundation for Science and Technology (FCT