Medications, youth therapeutic cultures and performance consumptions: a sociological approach

This article analyses performance consumptions among young people. The theme is explored along two main axes. The first concerns the social heterogeneity in this field, considered on two levels: the different purposes for those investments - cognitive/mental and physical performance; and the different social contexts - university and work - where performance practices and dispositions may be fostered. The second axis explores the roles of pharmacological and natural consumptions, and their interrelationship, in the dissemination of these practices. The empirical data for this analysis were drawn from an ongoing research project on performance consumptions among young people (aged 18-29 years) in Portugal, including both university students and young workers without university education. The results correspond to the stage of extensive research, for which a questionnaire was organised at a national level, using non-proportional quota sampling. On the one hand, they show that (a) there is a hierarchy of acceptance of consumptions according to their purposes, with cognitive/mental performance showing higher acceptance and (b) both pharmaceuticals and natural products are consumed for every type of performance investment. On the other, the comparison between students and workers introduces a certain heterogeneity in this general backdrop, both in terms of the purposes for their consumptions and their opting for natural or pharmacological resources. These threads of heterogeneity will prompt a discussion of the dynamics of pharmaceuticalisation within the field of performance, in particular how therapeutic cultures may be changing in terms of the way individuals relate to medications, expanding their uses in social life.

Professional exposure to fungal pathogens: an update to exposure conditions and exposure measurement

In many occupational settings an exposure to fungi occurs. Fungal exposure may occur for instance in the form of dermatocytes, yeasts or mold. Associated to the fungi themselves an exposure to cell wall components like ß(1 ? 3)-D-glucans, to mycotoxins or to microbial volatile compounds can occur. Health hazards may differ across species because fungi may produce different allergens and mycotoxins, and some species can infect humans. Occupational settings are often characterized by special exposure conditions with respect to duration, frequency and especially to the level of exposure resulting at least sometimes to high or very high fungal exposure. Because of these special conditions occupational settings are suitable for epidemiologic studies. However, the knowledge about occupational exposure to fungi and associated compounds like mycotoxins is still fragmentary and not well disseminated. An indication for a high fungal exposure is for instance the handling of dry natural products like grain, hay or herbal plants with a high specific surface and the tendency to release dust during handling. The fungal components often form the determinative part of such dusts and might be a vehicle to respiratory airways. The authors will present results of exposure measurements of occupational settings and exposure conditions which are only rarely investigated.

Biosynthesis and mode of action of ribosomally synthesized and post-translationally modified antimicrobial peptides

One of the greatest sources of biologically active compounds is natural products. Often these compounds serve as platforms for the design and development of novel drugs and therapeutics. The overwhelming amount of genomic information acquired in recent years has revealed that ribosomally synthesized and post-translationally modified natural products are much more widespread than originally anticipated. Identified in nearly all forms of life, these natural products display incredible structural diversity and possess a wide range of biological functions that include antimicrobial, antiviral, anti-inflammatory, antitumor, and antiallodynic activities. The unique pathways taken to biosynthesize these compounds offer exciting opportunities for the bioengineering of these complex molecules. The studies described herein focus on both the mode of action and biosynthesis of antimicrobial peptides. In Chapter 2, it is demonstrated that haloduracin, a recently discovered two-peptide lantibiotic, possesses nanomolar antimicrobial activity against a panel of bacteria strains. The potency of haloduracin rivals that of nisin, an economically and therapeutically relevant lantibiotic, which can be attributed to a similar dual mode of action. Moreover, it was demonstrated that this lantibiotic of alkaliphile origin has better stability at physiological pH than nisin. The molecular target of haloduracin was identified as the cell wall peptidoglycan precursor lipid II. Through the in vitro biosynthesis of haloduracin, several analogues of Halα were prepared and evaluated for their ability to inhibit peptidoglycan biosynthesis as well as bacterial cell growth. In an effort to overcome the limitations of in vitro biosynthesis strategies, a novel strategy was developed resulting in a constitutively active lantibiotic synthetase enzyme. This methodology, described in Chapter 3, enabled the production of fully-modified lacticin 481 products with proteinogenic and non-proteinogenic amino acid substitutions. A number of lacticin 481 analogues were prepared and their antimicrobial activity and ability to bind lipid II was assessed. Moreover, site-directed mutagenesis of the constitutively active synthetase resulted in a kinase-like enzyme with the ability to phosphorylate a number of peptide substrates. The hunt for a lantibiotic synthetase enzyme responsible for installing the presumed dehydro amino acids and a thioether ring in the natural product sublancin, led to the identification and characterization of a unique post-translational modification. The studies described in Chapter 4, demonstrate that sublancin is not a lantibiotic, but rather an unusual S-linked glycopeptide. Its structure was revised based on extensive chemical, biochemical, and spectroscopic characterization. In addition to structural investigation, bioinformatic analysis of the sublancin gene cluster led to the identification of an S-glycosyltransferase predicted to be responsible for the post-translational modification of the sublancin precursor peptide. The unprecedented glycosyltransferase was reconstituted in vitro and demonstrated remarkable substrate promiscuity for both the NDP-sugar co-substrate as well as the precursor peptide itself. An in vitro method was developed for the production of sublancin and analogues which were subsequently evaluated in bioactivity assays. Finally, a number of putative biosynthetic gene clusters were identified that appear to harbor the necessary genes for production of an S-glycopeptide. An additional S-glycosyltransferase with more favorable intrinsic properties including better expression, stability, and solubility was reconstituted in vitro and demonstrated robust catalytic abilities.

Biotechnological, nutritional and therapeutic uses of Pleurotus spp. (Oyster mushroom) related with its chemical composition: A review on the past decade findings

The particular characteristics of growth and development of mushrooms in nature result in the accumulation of a variety of secondary metabolites, several of them with biological activities. The genus Pleurotus is a cosmopolitan group of mushrooms with high nutritional value and therapeutic properties, besides a wide array of biotechnological and environmental applications. Scope and approach: The present report aims to provide a critical review on aspects related to chemical compounds isolated from the genus Pleurotus with possible biotechnological, nutritional and therapeutic uses. Investigations on the genus have immensely accelerated during the last ten years, so that only reports published after 2005 have been considered. Key findings and conclusions: The most important Pleurotus species cultivated in large scale are P. ostreatus and P. pulmonarius. However, more than 200 species have already been investigated to various degrees. Both basidiomata and mycelia of Pleurotus are a great renewable and easily accessible source of functional foods/nutraceuticals and pharmaceuticals with antioxidant, antimicrobial, anti-inflammatory, antitumor and immunomodulatory effects. A series of compounds have already been precisely defined including several polysaccharides, phenolics, terpenes and sterols. However, intensification of structure determination is highly desirable and demands considerable efforts. Further studies including clinical trials need to be carried out to ascertain the safety of these compounds as adequate alternatives to conventional drugs. Not less important is to extend the search for novel bioactives to less explored Pleurotus species.

In vivo antileishmanial activity and chemical profile of polar extract from Selaginella sellowii

The polar hydroethanolic extract from Selaginella sellowii (SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis.

Antiophidic Solanidane Steroidal Alkaloids from Solanum campaniforme

Three new solanidane alkaloids bearing a 22,23-epoxy ring (1-3) and four known compounds were isolated from leaves of Solanum campaniforme. The structures were determined using spectroscopic techniques, including ID and 2D NMR, and HRESIMS experiments. The antiophidic activity of the alkaloids was tested against Bothrops pauloensis venom. Compounds 1-3 completely inhibited myotoxicity without inhibiting phospholipase A(2) activity of the venom, while hemorrhage and skin necrosis were significantly reduced in the presence of alkaloids 1 and 2.

Medications, youth therapeutic cultures and performance consumptions: a sociological approach

"This article analyses performance consumptions among young people. The theme is explored along two main axes. The first concerns the social heterogeneity in this field, considered on two levels: the different purposes for those investments – cognitive/mental and physical performance; and the different social contexts – university and work – where performance practices and dispositions may be fostered. The second axis explores the roles of pharmacological and natural consumptions, and their interrelationship, in the dissemination of these practices. The empirical data for this analysis were drawn from an ongoing research project on performance consumptions among young people (aged 18−29 years) in Portugal, including both university students and young workers without university education. The results correspond to the stage of extensive research, for which a questionnaire was organised at a national level, using non-proportional quota sampling. On the one hand, they show that (a) there is a hierarchy of acceptance of consumptions according to their purposes, with cognitive/mental performance showing higher acceptance and (b) both pharmaceuticals and natural products are consumed for every type of performance investment. On the other, the comparison between students and workers introduces a certain heterogeneity in this general backdrop, both in terms of the purposes for their consumptions and their opting for natural or pharmacological resources. These threads of heterogeneity will prompt a discussion of the dynamics of pharmaceuticalisation within the field of performance, in particular how therapeutic cultures may be changing in terms of the way individuals relate to medications, expanding their uses in social life."

Microwave-assisted solvent extraction and analysis of shikimic acid from plant tissues.

A better method for determination of shikimate in plant tissues is needed to monitor exposure of plants to the herbicide glyphosate [N-(phosphonomethyl)glycine] and to screen the plant kingdom for high levels of this valuable phytochemical precursor to the pharmaceutical oseltamivir. A simple, rapid, and efficient method using microwave-assisted extraction (MWAE) with water as the extraction solvent was developed for the determination of shikimic acid in plant tissues. High performance liquid chromatography was used for the separation of shikimic acid, and chromatographic data were acquired using photodiode array detection. This MWAE technique was successful in recovering shikimic acid from a series of fortified plant tissues at more than 90% efficiency with an interference-free chromatogram. This allowed the use of lower amounts of reagents and organic solvents, reducing the use of toxic and/or hazardous chemicals, as compared to currently used methodologies. The method was used to determine the level of endogenous shikimic acid in several species of Brachiaria and sugarcane (Saccharum officinarum) and on B. decumbens and soybean (Glycine max) after treatment with glyphosate. The method was sensitive, rapid and reliable in all cases.

Avaliação da espécie vegetal Croton cajucara Benth como inibidor de biocorrosão em aço carbono Aisi 1020

Actually in the oil industry biotechnological approaches represent a challenge. In that, attention to metal structures affected by electrochemical corrosive processes, as well as by the interference of microorganisms (biocorrosion) which affect the kinetics of the environment / metal interface. Regarding to economical and environmental impacts reduction let to the use of natural products as an alternative to toxic synthetic inhibitors. This study aims the employment of green chemistry by evaluating the stem bark extracts (EHC, hydroalcoholic extract) and leaves (ECF, chloroform extract) of plant species Croton cajucara Benth as a corrosion inhibitor. In addition the effectiveness of corrosion inhibition of bioactive trans-clerodane dehydrocrotonin (DCTN) isolated from the stem bark of this Croton was also evaluated. For this purpose, carbon steel AISI 1020 was immersed in saline media (3,5 % NaCl) in the presence and absence of a microorganism recovered from a pipeline oil sample. Corrosion inhibition efficiency and its mechanisms were investigated by linear sweep voltammetry and electrochemical impedance. Culture-dependent and molecular biology techniques were used to characterize and identify bacterial species present in oil samples. The tested natural products EHC, ECF and DCTN (DMSO as solvent) in abiotic environment presented respectively, corrosion inhibition efficiencies of 57.6% (500 ppm), 86.1% (500 ppm) and 54.5% (62.5 ppm). Adsorption phenomena showed that EHC best fit Frumkin isotherm and ECF to Temkin isotherm. EHC extract (250 ppm) dissolved in a polar microemulsion system (MES-EHC) showed significant maximum inhibition efficiency (93.8%) fitting Langmuir isotherm. In the presence of the isolated Pseudomonas sp, EHC and ECF were able to form eco-compatible organic films with anti-corrosive properties

A bioengineered nisin derivative, M21A, in combination with food grade additives eradicates biofilms of Listeria monocytogenes

The burden of foodborne disease has large economic and social consequences worldwide. Despite strict regulations, a number of pathogens persist within the food environment, which is greatly contributed to by a build-up of resistance mechanisms and also through the formation of biofilms. Biofilms have been shown to be highly resistant to a number of antimicrobials and can be extremely difficult to remove once they are established. In parallel, the growing concern of consumers regarding the use of chemically derived antimicrobials within food has led to a drive toward more natural products. As a consequence, the use of naturally derived antimicrobials has become of particular interest. In this study we investigated the efficacy of nisin A and its bioengineered derivative M21A in combination with food grade additives to treat biofilms of a representative foodborne disease isolate of Listeria monocytogenes. Investigations revealed the enhanced antimicrobial effects, in liquid culture, of M21A in combination with citric acid or cinnamaldehyde over its wild type nisin A counterpart. Subsequently, an investigation was conducted into the effects of these combinations on an established biofilm of the same strain. Nisin M21A (0.1 μg/ml) alone or in combination with cinnamaldehyde (35 μg/ml) or citric acid (175 μg/ml) performed significantly better than combinations involving nisin A. All combinations of M21A with either citric acid or cinnamaldehyde eradicated the L. monocytogenes biofilm (in relation to a non-biofilm control). We conclude that M21A in combination with available food additives could further enhance the antimicrobial treatment of biofilms within the food industry, simply by substituting nisin A with M21A in current commercial products such as Nisaplin® (Danisco, DuPont).

Identification of endophytic bactéria from micropropagated yacon (Smallanthus sonchifolius) crowing under autotrophic and Heterotrophic systems.

Yacon, Smallanthus sonchifolius, an Andean species. is a rich source of dictetíc oligofructans with low glucose content. proteins and phenolic compounds. These constituents have shown efficacy in the prevention of diet-related ehronic diseases, including gastroin-testinal disorders and diabetes |1,2|. Yacon is part of a research program at the National Center for Natural Products Research (NCNPR) and University of Mississippi Field Station to develop new alternative root crops for Mississippi while attempting to im-prove the diet of low incorne families. Yacon can be easily propa-gated by cultings. Virus and nematode infections have been re-ported on plants propagated by cuttings in Brazil. a country that hás adopted Yacon as specialty crop [3|. We have developed two culture systems. autotrophic and heterotrophic, to produce healthy plants. Herem we describe the presence of endophytic bactéria m micropropagated Yacon. In auxin free media, new roots were induced. Overa 15day period. the average root mduction per expiam was 5.45 to 8.75 under autotrophic and heterotrophic cul-tures, respectively. Root lenglh vaned between 3 and 60mrn. The presence of root hairs and lateral roots was noticed only in auto-trophic condilions. These beneficiai bactéria were identified and chemically ctiaracterized. Acknowledgement: This research work was partially supported by the USDA/ARS Cooperative Research Agreement No. 58-6408-2-009. Referentes; |1) Terada S. et ai. (2006] Yakugaku Zasshi 126(8): 665-669. (2| Valentová K. Ulri-chová j. (2003) Biomedical Papers 147: 119-130. [3| Mogor C. et ai, (2003) Acta Horticulturea 597: 311 -313.

Antioxidant activity of jacaranda decurrens Cham.

Many diseases and related degenerative processes including heart, câncer and Parkinson diseases are associated with rcactive oxygen species (ROS). In an effort Io preveni diseases, search for com-pounds with antioxidant activity hás been a major interestof dif-ferent research groups in natural products research. The objective of this research was to investigatethe antioxidant activity of EtOH leaf extract ofjacarando decurrrens and its fractions using the 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) assay [lJ, that uses s pé ciro me t ric method to determine radical scavenging activity, Rutinattheconcçntrationof l.Omg-L was used as the standard. Our results ha vê shown lhat crude extract and fractions had anti-oxidant activities mainly if tested at concentrations of 5.0 to 10.0mg-L. such activities, however. were lesser or equal to the standard (Table 1). The triterpenes, ursolic and oleanohc acids, were detected in the crude extract, Jd-1 and Jd-2, Possibly, these triterpenes are the active constituents responsible for the antioxi-dant activity |2j. At lower concentrations (0,6mg-L than the standard. Jd-3 fraction was the most active. The presenceof flavo-noids and glycosilated compounds were detected in jcl-3 fraction (2], This is the first attempt to demonstrate antioxidant activities found i n Já cara n (ia decurrens leaf extracts. Acknowledgements. Re-search funded by FAPESP. The State of São Paulo Research Founda-tion. Brazil, Referentes: 11) Koleva I. et ai. (2002). Phytochem Anal. 13: 8-17, (2! Oh CJ, et ai. (2007)- Free Radie Rés. 41(6): 638-44.

New catalytic strategies for the manipulation of arenes

The aim of this Doctoral Thesis is the development of new catalytic synthetic methodologies in the context of the modern organic chemistry setting, with special focus on the use of cheap, sustainable catalytic materials. Specifically, during the course my PhD, I focused my research on two main distinct catalytic strategies, namely: the use of carbonaceous materials as catalysts (carbocatalysis) and nickel catalysis, also investigating a synergistic combination of the two. These methodologies were explored as means for the manipulation of (hetero)aromatic cores, representing ubiquitous, easily accessible and privileged scaffolds in medicinal or natural products chemistry. Both polar and radical reaction manifolds were engaged as complementary reactivities, capitalizing on metal- as well as organo-based activation modes. Particular attention has been devoted to addressing modern synthetic challenges or highly sought- after methodologies. Specifically, protocols for direct substitution of alcohols, dearomatization of arene nuclei, formation of C-S bonds, carbon dioxide fixation, C-C bond activation and fluoroalkylation were successfully achieved under carbo- or nickel catalyzed conditions.

La tutela penale dell'ambiente marino. Origini, sviluppo e tecniche di tutela nel contesto nazionale, sovranazionale e comparato.

La ricerca si propone di fornire un contributo allo studio del diritto penale dell’ambiente, prendendo in considerazione la disciplina penalistica che rileva nel caso di offesa – effettiva o potenziale – delle acque marine. Nello specifico – in ragione dei sempre più frequenti casi di inquinamento e disastro ambientale causati dalle immissioni di sostanze tossiche nelle acque marine, riconducibili alle attività di impresa ed alla navigazione – l’obiettivo del lavoro è quello di soffermarsi, partendo dalla dimensione internazionale ed europea del fenomeno, sulle disposizioni penali vigenti nel nostro ordinamento a salvaguardia delle risorse naturali marine, sulle modalità con cui le stesse sono tipizzate e sui possibili autori di tali reati, valutando – in termini più generali – se sia veramente effettivo l’attuale impianto nazionale di tutela oppure se non sia necessario ripensare il ruolo del diritto penale in tale settore. Per ampliare il contesto dell’indagine, verrà presa in considerazione la corrispondente disciplina francese, spagnola e statunitense; tale scelta si fonda sulla circostanza che i tre più significativi disastri ambientali marini della storia moderna si sono verificati rispettivamente a largo delle coste bretoni (petroliera Erika), galiziane (nave Prestige) e della Louisiana (piattaforma petrolifera Deep Water Horizon).

Computational investigation of a stereoselective synthesis of atropisomeric hydrazides possessing an N–N stereogenic axis

Axially chiral substrates are an interesting and widely studied class of compounds as they can be found in bioactive natural products and are employed as functional materials or as ligands in asymmetric catalytic processes. One branch of this family is the well-known world of the atropisomers. Among them, atropisomeric compounds possessing an N–N stereogenic axis are one truthfully fascinating system but not completely understood yet. In this thesis, we computationally investigated the mechanism of the diastereoselective formation of the N – N chiral axis of a hydrazide under asymmetric phase transfer catalytic conditions. Moreover, during this study, torsional barriers have been calculated for both the reagent and the product at the density functional theory (DFT). These values turned out to suitably match the experimental values and observations. Finally, Electronic Circular Dichroism (ECD) spectra have been simulated in order to assign the chiral absolute configuration to the products.