Back to plants for drug discovery: from ethnomedicine to more conventional approaches

Over the last years, there is rekindling of interest in drug discovery from botanical resources. This thesis proposed two different approaches (from ethnomedicine to scholarly strategies) for drug discovery from medicinal plants, identifying the areas of knowledge involved and addressing the challenges encountered, with the aim of enhancing the chance of success of the overarching process. The first approach consists to review the literature to increase understanding of a plant of interest and generate strong hypotheses for future drug development research on this plant. Illustrating such an approach, we focused on Tithonia diversifolia (Hemsl.) A. Gray (TD). Knowledge about TD was collected from both online databases and non-electronic resources. Overall, a total of 1,804 reports have been collected. After subsequent duplicates removal and screening for relevant titles and abstracts, a total of 119 text articles were obtained and assessed for eligibility. Finally, 168 articles were selected, of which forty-nine were added after analyses of the reference lists of the included papers. We found that all parts of the plant are valued in several cultures for a wide scope of ailments ranging from topical issues \u2014wounds, skeleto-muscular disorders, abscesses, dermatological conditions, and stomach pains\u2014 to systemic disorders such as diabetes, malaria, fever, hepatitis and infectious diseases. Importantly, most of the ethnomedical claims of TD have been substantiated in several studies conducted in vitro and in vivo in animals. Sometimes, findings were conflicting and thanks to this review, we were able to assess the weight of evidence for each pharmacological effect of TD. The anti-inflammatory, antimalarial, antidiabetic, antioxidant and anticancer effects do stand out but there is also a stunning array of other relevant pharmacological effects. Chemically, a hundred of chemicals, mainly terpenoids and phenols, have been isolated from various TD extracts so far. Of these, some compounds including Tagitinin C have been linked to the pharmacology of TD. About the toxicological profile, we were able to conclude based on evidence that short-term oral administration of TD is relatively well-tolerated in animals when taken at doses less than 100 mg/kg. The second approach consists to screen the ethnomedical knowledge of indigenous people to select the best plant candidate to launch a drug discovery campaign. So, we carried out a 6-month cross-sectional questionnaire-based survey to explore the use of medicinal plants (MP) in People living with HIV (PLHIV) in the city of Dschang (West Region, Cameroon). Of the 247 HIV-infected respondents, 54.9% reported to use plants. MP users were then kindly invited to provide photographs and/or specimens of plants for botanical identification. A total of 70 MP, chiefly the herbs, were mentioned by informants (82.2% of total MP users, mean\ub1SEM: 2.2\ub10.2 MP/subject, min 1, max 11), of which forty-nine have been botanically identified. Commonly reported pathological conditions or symptoms treated with MP included malaria (n = 27, 18.4% of total citations), cough (n = 20, 13.6%) and abdominal pain (n = 16, 10.9%). The benefits of using MP reportedly ranged from moderate (n = 60, 57.7%) to complete (n = 35, 33.7%) relief, while only 8 subjects (7.7% of MP users) reported no change in their terms. Interestingly, 2 subjects (33.3 % of respondents) denounced fatigue and weight loss. We also observed that THPs were the main advisors of PLHIV on the use of MP. Thus, in the rest of our study, their knowledge and attitudes towards HIV/AIDS were surveyed aiming at understanding whether they may be an appropriate resource to assist in the scaling up of HIV prevention and treatment delivery services in Cameroon. 16 THPs were recruited by the chairperson of the Cooperative Society of Producers of Medicinal Plants of West Region based on their good reputation in traditional healing practice. Three of them acknowledged the use of MP to manage HIV diseases in their clients. All THPs who agreed to participate in the survey were also evaluated for their knowledge of HIV transmission, prevention and diagnosis. We found that their knowledge related to HIV was relatively low raising concern about their aptitude to effectively assist conventional health practitioners in fighting against HIV/AIDS. Resulting from literature mining and ethnomedical claims is the adoption of a relevant pharmacological testing system. In any case, the testing systems should represent the biological activities that best match the ethnomedical uses of the selected plant species. In addition, it is important to bear in mind that plant extracts are complex mixtures containing various components and, therefore, their overall activity results from interactions between their naturally occurring ingredients. It is with this background that we conducted a study of comparison of the effects of a whole extract of a particular strain of Cannabis sativa L. to that of cannabidiol (CBD). We knew cannabis is endowed with a potent anti-inflammatory effect attributable mainly to CBD, but also to its entourage. This mechanism by which other compounds occurring in cannabis may contribute to its clinical effects has been espoused as an \u201centourage effect\u201d. The concept of entourage effect was first introduced in 1998 by Ben-Shabat and Raphael Mechoulam but still, there was no hard evidence that the entourage effect is real. So, thanks to a collaboration with a pharmaceutical company, we grew a particular strain of cannabis deprived of THC and standardized in 5% CBD (CM5). Then, we tested the effects of an extract of CM5 in parallel to that of pure CBD at equimolar concentrations on neutrophil functions including oxidative metabolism, migration and production of proinflammatory cytokines. Results show that CM5 0.05-50 \u3bcg/mL and CBD 10-8-10-5 M inhibit the neutrophil functions including ROS production, cell migration, mRNA levels of proinflammatory cytokines (but at the protein level, only TNF-a was inhibited) to a comparable extent, indicating that CBD may be the main responsible of the anti-inflammatory effects of Cannabis. The effects of CBD and CM5 show however remarkable differences in terms of potency and efficacy, suggesting that beyond CBD, other components of cannabis may contribute to its biological effects. As a whole, such results support the use of cannabis and CBD to stem inflammation, however also warrant in-depth investigation of the underlying cellular and molecular mechanisms to better exploit their therapeutic potential

Obtaining bioactive compounds from Curcuma longa L. and Lippia alba M. by supercritical technology: global yilds, extraction kinetic, chemical composition, and usage of the starch residue

Orientador: Maria Angela de Almeida MeirelesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de AlimentosResumo: Os compostos bioativos têm sido alvo de estudos, devido aos seus benefícios comprovados como fonte primária na prevenção de doenças, através da ingestão de alimentos funcionais. Algumas espécies utilizadas como fonte destes compostos são encontradas na alimentação diária, compondo as especiarias e plantas aromáticas e corantes naturais. Dentre as diversas espécies conhecidas cita-se a cúrcuma (Curcuma longa L.) e a falsa melissa (Lippia alba M.), que apresentam atividades farmacológicas comprovadas como atividade anticâncer, antiinflamatória e anticolinasterase, utilizadas no tratamento de câncer e Alzheimer, respectivamente. O objetivo deste trabalho foi identificar os parâmetros de processo da extração com fluido supercrítico (SFE) para maximização do rendimento de extratos da Curcuma longa L. e Lippia alba M., e comparar a outras metodologias convencionais de extração como hidrodestilação (HD), soxhlet (SoE) e extração com solventes orgânicos a baixa pressão (LPSE). Para a avaliação dos processos foram utilizadas as taxas de extração, tempo de processo, rendimento global de extração e perfil fitoquímico dos extratos, propriedades funcionais como atividade antiproliferativa e antimicobacteriana. Os experimentos foram conduzidos numa unidade de Extração Supercrítica (SFE) com extrator de leito fixo com diâmetro de 2,74×10¿2 m e comprimento de 0,375 m. Para a cúrcuma os experimentos foram realizados a 30 ºC e 300 bar; a mistura de etanol e isopropanol, na proporção 1:1, foi usada como co-solvente. Foram estudados os efeitos da variação da geometria do leito, ou seja, da relação altura/diâmetro do leito (HB/DB), da extração acelerada com solvente e período estático, e extração fracionada. Os extratos foram analisados por CG-DIC, CCD e Espectrofotômetro-UV. Na razão HB/DB de 1,8 obteve-se o maior rendimento em curcuminóides; maiores rendimentos em curcuminóides também foram obtidos com o uso de 50% de co-solvente com período estático de 30 minutos. O maior rendimento obtido na extração supercrítica de falsa melissa foi de aproximadamente 7 % (massa), as extrações a baixa pressão e por Soxhlet obtiveram altos rendimentos (17 e 20%, respectivamente), porém muitas substâncias indesejáveis foram co-extraídas. Para a obtenção dos compostos de interesse da falsa melissa, as melhores condições da SFE foram 80 bar/ 45 ºC para a obtenção de carvona (80%, massa) e 120 bar/45 ºC para a obtenção de limoneno (17%, massa); para todas as metodologias testadas a extração supercrítica promoveu a melhor extração de carvona e a hidrodestilação a extração do limoneno. O amido residual do processo de extração de oleoresina de cúrcuma e gengibre, que podem ser utilizados como amidos especiais, foram observados quanto às suas características físico-químicas e comparados, com amidos comerciais. A fração volátil do extrato de cúrcuma apresentou atividade antiproliferativa seletiva para as células cancerosas de mama e ovário, pulmão, próstata e cólon. A atividade antimicobacteriana foi identificada em todos os extratos de cúrcuma, independente da concentração dos curcuminóidesAbstract: Bioactive compounds have been target of studies due to benefits proved as primary source to prevent diseases, through the intake of functional foods. Some species used as compounds bioactive source are presents in dairy foods, which are inside the category of spices, aromatic plants and natural colors. Among many species known, there are turmeric (Curcuma longa L.) and ¿falsa melissa¿ (Lippia alba M.), that have pharmacological activities as anticancer, anti-inflammatory and anticolinasterase activities used on cancer and Alzheimer treatments, respectively. The objective of this work was identify the process parameters of supercritical fluid extraction (SFE) for maximization of the extracts yield of Curcuma longa L. and Lippia alba M., and to compare to other conventional methodologies of extraction as hydrodistillation (HD), Soxhlet (SoE) and low pressure solvent extraction (LPSE) with organic solvents. As a methodology to evaluate the process, some process parameters were used as extraction rate, process time, global extraction yield and phytochemical profile of extracts, some functional properties as antiproliferative and antimycobacterial activities. The essays were conducted in the SFE Unity with fix bed extractor (2.74×10¿2 m of diameter and 0.375 m of length). The turmeric essays were made at 30 ºC and 300 bar; the mixture of ethanol and isopropyl alcohol was used (1:1) as cosolvent. The effects of the bed geometry were studied, in other words, the ratio of bed height / bed diameter (HB/DB); the accelerated solvent extraction and fractioned extraction as well as the effects of the static period were also studied. The extracts were analyzed using GC-FID, TLC and Spectrophotometer ¿ UV. The essay done with HB/DB =1.8 showed the largest yield in curcuminoids; using 50% of cosolvent and static period was also possible to obtain higher contents of curcuminoids. The maximum extract yield obtained for SFE from the ¿falsa melissa¿ was approximately 7% (mass), the LPSE and Soxhlet extraction had very high yields (17 and 20%, respectively), but many undesirable compounds were extracted. To obtain the target compounds of ¿falsa Melissa¿, the best conditions for SFE were 80 bar/45 ºC to obtain large amounts of carvona (80%, mass) and 120 bar/45 ºC to obtain large amounts of limonene (17%, mass); the highest yield in carvone was obtained by the SFE process while the largest yield in limonene was obtained in the hydrodistillation process. The residual starch from SFE process used to obtain turmeric and ginger oleoresins, which can be used as special starches, were observed with their chemical and physical characteristics and compared to industrial starches. The volatile fraction of turmeric extracts showed antiproliferative activity selective for cancers cells of breast and ovary, lung, prostate and colon. The antimycobacterial activity was identified among all turmeric extracts, independently of curcuminoids concentrationDoutoradoDoutor em Engenharia de Alimento

Kinetics and optimization of process for isolation of plant extracts with antibacterial activity

Cilj ove doktorske disertacije bio je ispitivanje kinetike izolacije ekstrakata sa jakim antibakterijskim delovanjem iz biljnog materijala primenom različitih postupaka ekstrakcije. Za izolaciju bioaktivnih supstanci korišćena je natkritična ekstrakcija sa ugljenik(IV)-oksidom, hidrodestilacija i ekstrakcija etanolom sa i bez primene ultrazvuka. Predmetom istraživanja ove doktorske disertacije obuhvaćena je analiza i optimizacija različitih procesa izolacije, kao i ispitivanje sadržaja aktivnih komponenti i/ili antibakterijskog dejstva dobijenih ekstrakta za primenu u farmaceutskoj i/ili prehrambenoj industriji. U eksperimentima je, kao sirovina, korišćeno odabrano začinsko i lekovito bilje (Rosmarinus officinalis, Salvia officinalis, Thymus vulgaris, Origanum vulgare, Eugenia caryophyllata, Laurus nobilis, Angelica archangelica, Echinacea angustifolia, Verbascum thapsus, Calendula officinalis i Aloe barbadensis Miller), lišaj Usnea barbata i odabrane mešavine biljnog materijala (karanfilić/origano i karanfilić/timijan). U disertaciji je posebno ispitana i analizirana kinetika procesa natkritične ekstrakcije. S tim u vezi, ispitivan je uticaj operativnih parametara (pritiska i temperature) i odgovarajućeg predtretmana biljnog materijala sa natkritičnim ugljenik(IV)-oksidom na kinetiku natkritične ekstrakcije, kao i uticaj prisustva pojedinih biljnih sirovina u smeši (njihovih glavnih komponenata) na povećanje moći rastvaranja natkritičnog ugljenik(IV)- oksida (kosolventski efekat), pa samim tim i na povećanje brzine ekstrakcije i smanjenje potrošnje natkritičnog fluida. U disertaciji su, takođe, prikazani rezultati ispitivanja kinetike ekstrakcije etanolom sa i bez primene ultrazvuka. Za simulaciju procesa natkritične ekstrakcije iz pojedinačnih biljnih sirovina i izabranih mešavina biljnog materijala korišćeni su postojeći matematički modeli zasnovani na diferencijalnom bilansu mase (Stamenic i sar., 2008; Zizovic i sar., 2005; Sovova i sar., 1994a) i na analogiji sa prenosom toplote (Bartle i sar., 1990; Hong i sar., 1990; Reverchon i sar., 1994 i 1993). Odgovarajući parametri dobijeni primenom navedenih matematičkih modela, zajedno sa podacima o hemijskom sastavu, korišćeni su za interpretaciju fenomena prenosa mase u čvrstoj fazi i u filmu natkritičnog ugljenik(IV)-oksida do kojih dolazi tokom procesa natkritične ekstrakcije iz pojedinih biljnih sirovina i izabranih mešavina biljnog materijala. Za modelovanje procesa ekstrakcija sa etanolom korišćeni su postojeći modeli izvedeni iz drugog Fikovog zakona u cilju određivanja koeficijenata difuzije ekstraktivnih materija u čvrstoj fazi (Crank, 1975; Treybal, 1968). Za rešavanje jednačina navedenih matematičkih modela korišćen je softverski paket Microsoft Fortran PowerStation 4.0. Za ispitivanje antibakterijskog delovanja biljnih ekstrakata i etarskih ulja korišćenа је modifikovanа mikrodiluciona ili makrodiluciona metoda u bujonu opisana i preporučena od strane CLSI (Clinical Laboratory Standards Institute, 2008, SAD), koja se u rutinskoj laboratorijskoj praksi koristi za ispitivanje antibakterijskog delovanja antibiotika, tj. za određivanje vrednosti MIC (minimalne inhibitorne koncentracije) antibiotika. Antibakterijsko delovanje biljnih ekstrakata ispitivano је na sojevima: Staphylococcus vrsta, uključujući sojeve Staphylococcus aureus koji su rezistentni na meticilin (MRSA), Enterococcus vrsta (uključujući vankomicin rezistentne enterokoke, VRE), Streptococcus, Bacillus i Geobacillus vrsta. Ispitan je uticaj pojedinih ekstrakta i na sojeve Gram-negativnih bakterija, Е.coli, Enterobacter cloacae i Sallmonela Enteritidis...This study was aimed to investigate kinetics of isolation of the extracts with strong antibacterial activity from plant material by using different extraction processes. The bioactive substances from plant matrial were isolated by supercritical carbon dioxide extraction, hydrodistillation and ethanol extraction with and without ultrasound. The scope of the present study was kinetic analysis and optimization of different extraction processes as well as content of active substance and/or antibacterial activity of isolated supercritical extracts for application in pharmaceutical and/or food industry. Selected herbs and spices (Rosmarinus officinalis, Salvia officinalis, Thymus vulgaris, Origanum vulgare, Eugenia caryophyllata, Laurus nobilis, Angelica archangelic), Echinacea angustifolia, Verbascum thapsu, Calendula officinalis, Aloe barbadensis Miller), lichen Usnea barbata and selected mixtures of plant materials (clove/oregano and clove/thymus) were used as raw material for experiments. In this study, supercritical carbon dioxide extraction kinetics was particularly analyzed. Therewith, influence of operating parameters (pressure and temperature) and pretreatment of the plant material with supercritical carbon dioxide on the supercritical extraction kinetics, influence of presence of particular plant material in the mixtures of plants (their main components) on the solubility power of supercritical carbon dioxide (co-solvent effect) and subsquently on increase of extraction rate and reduction of supercritical fluid consumption was investigated in this work as well. The results of investigation of the kinetics of ethanol extractions are also presented here. Mathematical models based on differential mass balance (Stamenic et al., 2008; Zizovic et al., 2005; Sovova et al., 1994a,b) and heat transfer analogy (Bartle et al., 1990; Hong et al., 1990; Reverchon et al., 1994, 1993) were used for simulation of process of supercritical carbon dioxide extraction from pure plants and chosen mixture of plants for evaluation of parameters that can be used for interpretation of the mass transfer phenomena in the solid and supercritical carbon dioxide phase. Mathematical models based on the Second Fick’s Law were used for simulation of ethanol extractions in order to evaluate coefficients of diffusion of extractible substances in solid phase (Crank, 1975; Treybal, 1968). Solution of the equations of above metioned mathematical models were solved using Microsoft Fortran PowerStation 4.0. For antibacterial susceptibility testing, modified broth microdilution оr macrodilution method was applied in accordance with the prescription of CLSI (Clinical Laboratory Standards Institute, 2008, USA and corresponding MIC (minimal inhibitory concentration) values were determined. Antibacterial effect of plant extracts on Staphylococcus species including meticillin-resistant Staphylococcus aureus (MRSA) bacterial strains as well as Enterococcus (including vancomycin resistant strains–VRE), Streptococcus, Bacillus and Geobacillus species was investigated. Antibacterial activity of extracts on the Gram-negative bacteria such as Е.coli, Enterobacter cloacae and Sallmonela Enteritidis was investigated as well..

Bioactive Compounds from Natural Products: Separation, Characterization and Applications

Dear colleagues, This Special Issue aims to publish new and innovative research that could demonstrate the therapeutic potential of natural health products, through relevant in vitro and/or in vivo biological activities, to prevent or alleviate degenerative diseases. The interaction of natural health products with human microbiota represents an essential aspect, because it could modulate the microbial pattern and alleviate more of a chronic disease’s effects in the case of type 2 diabetes, cardiovascular dysfunctions, neurodegenerative diseases, and inflammatory colon pathologies. Additionally, you are invited to send research based on the effect of different extracts or functional foods used in degenerative pathologies and interactions with human microbiota. We aim to identify new data on in vitro/in vivo research that could demonstrate the bioavailability of natural compounds and the relationship with antioxidant/antimicrobial capacity. Modulated microbiota aspects are expected to be published based on the interaction with natural compounds, natural sweeteners, or other molecules that influence the colon health status

Understanding the colloidal and aromatic stability of dry-hopped beer

This thesis documents investigations of flavour stability and sporadic haze formation. Historical data was collected to statistically assess process derivations impacting sporadic increases in turbidity. Spearman’s rank-order correlation coefficients did not find significant relationships between brewing, conditioning, and filtration/packaging on the increase of turbidity. Therefore, diagnostic studies were used to gradually eliminate potential sources of observed sporadic spikes in turbidity. Concentrations of high molecular weight β-glucans, total protein, and polyphenol were measured in low (≤ 5.0 EBC), high (≥ 5.0 EBC), and control (different brand, always ≤3.0 EBC) samples. Additionally, beer samples were digested with Ultraflo®Max, amyloglucosidase, and pepsin to digest β-glucans, residual starches/dextrins, and protein, respectively. The enzymatic digestion studies saw the greatest differences pre and post digestion by the addition of pepsin. The wet-chemical tests revealed that only β-glucan contents were elevated in high haze samples. Results indicated that mannoproteins were a culprit of turbidity. The use of LC-QTOF-MS and an assay for D-mannose, D-fructose, and D-glucose confirmed this supposition. Flavour-stability studies examined the solubility and extraction rate of hop terpenes into beer, the use of sensory analysis to trace the change in flavour/aroma over time, and an assay-development for the quantification of terpene concentrations in beer. As each hop variety contained different essential oil compositions, a linear extraction rate could not be determined. In addition to this, the chemistry of each hop terpene/terpenoid differs in chemical composition and are more/less soluble in different concentrations of ethanol. Overall, sensory and analytical data analyses did not find any strong relationships. However, the presence of β-myrcene could be linked to fresh beer less than 14 days old. Finally, the Vanillin assay was adapted to develop an assay to determine the concentration of terpenes/terpenoids in beer. Unfortunately, terpene concentrations in beer are too low to be detectable in the assay and the isolation/concentration methods were not successful. However, there is future potential to develop the assay by utilising methanol in place of ethanol and assessing one class of terpenes, such as monoterpene oxides, instead of multiple classes of terpenes. The combined results of this work provide more information to brewers, packaging technologists, and quality laboratories on how raw materials impact the quality of the final product, and therefore increasing the likelihood of consumers experiencing high quality, flavour stable products

Bio-Functional Natural Products in Edible Resources for Human Health and Beauty

Natural products remain important repositories of promising therapeutic candidates due to their rich chemical and biological diversity. The Special Issue on "Bio-functional Natural Products in Edible Resources for Human Health and Beauty" is intended to offer biological active natural products from edible resources as candidates and/or leads for pharmaceuticals, dietary supplements, functional foods, cosmetics, and food additives, etc. The research fields of this Special Issue include natural products chemistry, phytochemistry, pharmacognosy, food chemistry, bioorganic chemistry, chemical biology, molecular biology, molecular pharmacology, and other related research fields of bioactive natural products obtained from the edible resources. This eBook contains 12 Reviews and Articles focusing on these research areas. I hope that this eBook will be of benefit to outstanding professionals in these research areas

Advances in Phytochemistry, Textile and Renewable Energy Research for Industrial Growth

The International Conference on Phytochemistry, Textile, & Renewable Energy Technologies for Sustainable Development (ICPTRE 2020) was hosted by the World bank funded Africa Centre of Excellence in Phytochemicals, Textile and Renewable Energy (ACEII-PTRE) based at Moi University in conjunction with Donghua University, China and the Sino–Africa International Symposium on Textiles and Apparel (SAISTA). The theme of the conference was Advancing Science, Technology and Innovation for Industrial Growth. The research relationships between universities and industry have enabled the two entities to flourish and, in the past, have been credited for accelerated sustainable development and uplifting of millions out poverty. ICPTRE 2020 therefore provided a platform for academic researchers drawn from across the world to meet key industry professionals and actively share knowledge while advancing the role of research in industrial development, particularly, in the developing nations. The conference also provided exhibitors with an opportunity to interact with professionals and showcase their business, products, technologies and equipment. During the course of the conference, industrial exhibitions, research papers and presentations in the fields of phytochemistry, textiles, renewable energy, industry, science, technology, innovations and much more were presented

Anuário Científico – 2009 & 2010 Resumos de Artigos, Comunicações, Teses, Patentes, Livros e Monografias de Mestrado

O Conselho Técnico-Científico do Instituto Superior de Engenharia de Lisboa (ISEL), na senda da consolidação da divulgação do conhecimento e da ciência desenvolvidos pelo nosso corpo docente, propõe-se publicar mais uma edição do Anuário Científico, relativa à produção científica de 2009 e 2010. A investigação, enquanto vertente estratégica do Instituto Superior de Engenharia de Lisboa (ISEL), tem concorrido para o seu reconhecimento nacional e internacional como instituição de referência e de qualidade na área do ensino das engenharias. É também nesta vertente que o ISEL consubstancia a sua ligação à sociedade portuguesa e internacional através da transferência de tecnologia e de conhecimento, resultantes da sua atividade científica e pedagógica, contribuindo para o seu desenvolvimento e crescimento de forma sustentada. São parte integrante do Anuário Científico todos os conteúdos com afiliação ISEL resultantes de resumos de artigos publicados em livros, revistas e atas de congressos que os docentes do ISEL apresentaram em fóruns e congressos nacionais e internacionais, bem como teses e patentes. Desde 2002, ano da publicação da primeira edição, temos assistido a uma evolução crescente do número de publicações de conteúdos científicos, fruto do trabalho desenvolvido pelos docentes que se têm empenhado com afinco e perseverança. Contudo, nestes dois anos (2009 e 2010) constatou-se um decréscimo no número de publicações, principalmente em 2010. Uma das causas poderá estar diretamente relacionada com a redução do financiamento ao ensino superior uma vez que limita toda a investigação no âmbito da atividade de I&D e da produção científica. Na sequência da implementação do Processo de Bolonha em 2006, o ISEL promoveu a criação de cursos de Mestrado disponibilizando uma oferta educativa mais completa e diversificada aos seus alunos, mas também de outras instituições, dotando-os de competências inovadoras apropriadas ao mercado de trabalho que hoje se carateriza mais competitivo e dinâmico. Terminados os períodos escolar e de execução das monografias dos alunos, os resumos destas são igualmente parte integrante deste Anuário, no que concerne à conclusão dos Mestrados em 2009 e 2010.A fim de permitir uma maior acessibilidade à comunidade científica e à sociedade civil, o Anuário Científico será editado de ora avante em formato eletrónico. Excecionalmente esta edição contempla publicações referentes a dois anos – 2009 e 2010