Inhibition of adventitious rooting in Backhousia citriodora F. Muell cuttings correlate with the concentration of essential oil

Backhousia citriodora is typical of the many commercially valuable woody Australian Myrtaceae species that are recalcitrant in forming adventitious roots from cuttings after maturation. A series of experiments were conducted to identify an endogenous rooting inhibitor in line with established criteria. Endogenous levels of citral were correlated with the rooting capacities of juvenile versus mature, and easy- versus difficult-to-root genotypes of B. citriodora, in both winter and summer. The biological activity of citral was confirmed in bioassays on mung beans and easy-to-root B. citriodora seedlings. Evidence of a common mechanism of root inhibition with other species in the Myrtaceae and the role of action of citral are discussed.

Toward a better understanding of the influences on physical activity: The role of determinants, correlates, causal variables, mediators, moderators, and confounders

Background: For research on physical activity interventions to progress systematically, the mechanisms of action must be studied. In doing so, the research methods and their associated concepts and terminology become more complex. It is particularly important to clearly distinguish among determinants, correlates, mediators, moderators, and confounder variables used in physical activity research. This article examines the factors that are correlated with and that may have a causal relationship to physical activity. Methods and Results: We propose that the term correlate be used, instead of determinant, to describe statistical associations or correlations between measured variables and physical activity. Studies of the correlates of physical activity are reviewed. The findings of these studies can help to critique existing theories of health behavior change and can provide hypotheses to be tested in intervention studies from which it is possible to draw causal inferences. Mediator, moderator, and confounder variables can act to influence measured changes in physical activity. Intervening causal variables that are necessary to complete a cause-effect pathway between an intervention and physical activity are termed mediators. The relationship between an intervention and physical activity behaviors may vary for different groups; the strata by which they vary are levels of moderators of the relationship. Other factors may distort or affect the observed relationships between program exposure and physical activity, and are known as confounders. Conclusions: Consistent use of terms and additional research on mediators and moderators of intervention effects will improve our ability to understand and influence physical activity.

Hepatic xenobiotic metabolism of cylindrospermopsin in vivo in the mouse

Cylindrospermopsin (CYN) is a hepatotoxin isolated from the blue-green alga Cylindrospermopsis raciborskii. The role of both glutathione (GSH) and the cytochrome P450 enzyme system (P450) in the mechanism of toxicity of CYN has been previously investigated in in vitro systems. We have investigated the role of GSH and P450 in vivo in mice. Mice pre-treated with buthionine sulphoximine and diethyl maleate to deplete hepatic GSH prior to dosing with 0.2 mg/kg CYN showed a seven-day survival rate of 5/13 while the control group rate was 9/14. Dosing mice with 0.2 mg/kg CYN produced a small decrease in hepatic GSH with a characteristic rebound effect at 24 h, The magnitude of this effect is however small and combined with the non-significant difference in survival rates after GSH depletion suggest depletion of GSH by CYN could not be a primary mechanism for CYN toxicity, Conversely, pro-treatment with piperonyl butoxide, a P450 inhibitor, protected mice against CYN toxicity giving a survival rate of 10/10 compared with 4/10 in the control group (p < 0.05 Chi squared) and was protective at doses up to 0.8 mg/kg, suggesting activation of CYN by P450 is of primary importance in the mechanism of action. (C) 2002 Elsevier Science Ltd. All rights reserved.

Fondaparinux verses enoxaparin for the prevention of venous thromboembelism

Venous thromboembolism is a frequent, life-threatening, postoperative complication of hip-fracture and total-knee-replacement surgery. Fondaparinux is a synthetic polysaccharide that selectively binds to antithrombin, the primary endogenous regulator of blood coagulation. Low molecular weight heparins, such as enoxaparin, are less specific inhibitors of coagulation. In patients undergoing hip-fracture surgery, fondaparinux is more effective than once-daily enoxaparin as prophylaxis for venous thromboembolism. Fondaparinux (25 mg/day s.c.) was also more effective than enoxaparin (30 mg s.c. b.i.d.) as prophylaxis for venous thromboembolism in elective knee surgery. These differences may be explained by the fact that there is less prophylaxis cover with enoxaparin, as it has a much shorter duration of action than fondaparinux. Thus, with the present dosing regimens, fondaparinux is probably preferable to enoxaparin for the prevention of venous thromboembolism.

Purification and characterisation of functional early pregnancy factor expressed in Sf9 insect cells and in Escherichia coli

Early pregnancy factor (EPF) is a secreted protein with growth regulatory and immunomodulatory properties. It is an extracellular form of the mitochondrial matrix protein chaperonin 10 (Cpn10), a molecular chaperone. An understanding of the mechanism of action of EPF and an exploration of therapeutic potential has been limited by availability of purified material. The present study was undertaken to develop a simple high-yielding procedure for preparation of material for structure/function studies, which could be scaled up for therapeutic application. Human EPF was expressed in Sf9 insect cells by baculovirus infection and in Escherichia coli using a heat inducible vector. A modified molecule with an additional N-terminal alanine was also expressed in E coli. The soluble protein was purified from cell lysates via anion exchange (negative-binding mode), cation exchange, and hydrophobic interaction chromatography, yielding similar to42 and 36 mg EPF from 300 ml bacterial and I L Sf9 cultures, respectively. The preparations were highly purified ( greater than or equal to99% purity on SDS-PAGE for the bacterial products and greater than or equal to97% for that of insect cells) and had the expected mass and heptameric structure under native conditions, as determined by mass spectrometry and gel permeation chromatography, respectively. All recombinant preparations exhibited activity in the EPF bioassay, the rosette inhibition test, with similar potency both to each other and to the native molecule. In two in vivo assays of immuno suppressive activity, the delayed-type hypersensitivity reaction and experimental autoimmune encephalomyelitis, the insect cell and modified bacterial products, both with N-terminal additions (acetylation or amino acid), exhibited similar levels of suppressive activity, but the bacterial product with no N-terminal modification had no effect in either assay. Studies by others have shown that N-terminal addition is not necessary for Cpn10 activity. By defining techniques for facile production of molecules with and without immunosuppressive properties, the present studies make it possible to explore mechanisms underlying the distinction between EPF and Cpn10 activity. (C) 2003 Elsevier Inc. All rights reserved.

Synthesis and characterization of delta-atracotoxin-ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus)

delta-Atracotoxin-Ar1a (delta-ACTX-Ar1a) is the major polypeptide neurotoxin isolated from the venom of the male Sydney funnel-web spider, Atrax robustus. This neurotoxin targets both insect and mammalian voltage-gated sodium channels, where it competes with scorpion alpha-toxins for neurotoxin receptor site-3 to slow sodium-channel inactivation. Progress in characterizing the structure and mechanism of action of this toxin has been hampered by the limited supply of pure toxin from natural sources. In this paper, we describe the first successful chemical synthesis and oxidative refolding of the four-disulfide bond containing delta-ACTX-Ar1a. This synthesis involved solid-phase Boc chemistry using double coupling, followed by oxidative folding of purified peptide using a buffer of 2 M GdnHCl and glutathione/glutathiol in a 1:1 mixture of 2-propanol (pH 8.5). Successful oxidation and refolding was confirmed using both chemical and pharmacological characterization. Ion spray mass spectrometry was employed to confirm the molecular weight. H-1 NMR analysis showed identical chemical shifts for native and synthetic toxins, indicating that the synthetic toxin adopts the native fold. Pharmacological studies employing whole-cell patch clamp recordings from rat dorsal root ganglion neurons confirmed that synthetic delta-ACTX-Ar1a produced a slowing of the sodium current inactivation and hyperpolarizing shifts in the voltage-dependence of activation and inactivation similar to native toxin. Under current clamp conditions, we show for the first time that delta-ACTX-Ar1a produces spontaneous repetitive plateau potentials underlying the clinical symptoms seen during envenomation. This successful oxidative refolding of synthetic delta-ACTX-Ar1a paves the way for future structure-activity studies to determine the toxin pharmacophore.

The Utility of the Human Security Agenda for Policy-makers

The idea of “human security” is gaining attention among policy-makers and security analysts. Little scholarly attention has been given to the questions of why states accept (or reject) a human security agenda or how such an agenda is incorporated into policy practices. The article suggests that a human security approach is most likely to be applied when both humanitarian and national interests combine. Yet when states or organisations adopt a human security approach, they often misjudge the complex and long-term commitment required of such an approach. There is also the potential for such an agenda to be manipulated to justify questionable courses of action. These issues frame an analysis of six recent case studies.

Contribution towards a reflection about methodological strategies in design education and the function of drawing in design

This work presents a reflection on Design education and specifically on the role of Drawing in this area. As a subject, Design has expanded its field of action expanding into new areas such as Experience Design or Service Design. It became necessary for the designer to have more than an education based on technological knowledge or know-how. Many authors like Meredith Davis, Don Norman or Jamie Hobson point out the urgency to review the curricula of Design courses because nowadays “… design is more than appearance, design is about interaction, about strategy and about services. Designers change social behavior” (Norman 2011). When shifting from a product-centered design to a person-centered design (in a structure, a service or in a relationship) what should the function of drawing in a design course be? What should its curriculum be? Our work methodology will be to confront today’s perspectives on design theory and practice in an attempt to add to the discussion on the methodological strategies in design teaching in the contemporary context.

Contribution towards a reflection about methodological strategies in Design Education and the function of Drawing in Design

This work presents a reflection on Design education and specifically on the role of Drawing in this area. As a subject, Design has expanded its field of action expanding into new areas such as Experience Design or Service Design. It became necessary for the designer to have more than an education based on technological knowledge or know-how. Many authors like Meredith Davis, Don Norman or Jamie Hobson point out the urgency to review the curricula of Design courses because nowadays “ … design is more than appearance, design is about interaction, about strategy and about services. Designers change social behavior” (Norman, 2011) When shifting from a product-centered design to a person-centered design (in a structure, a service or in a relationship) what should the function of drawing in a design course be? What should its curriculum be? Our work methodology will be to confront today’s perspectives on design theory and practice in an attempt to add to the discussion on the methodological strategies in design teaching in the contemporary context.

Policies for decentralization and development of health education

How the policy of action and professional standards have influenced the development and decentralization of health education is discussed. It is concluded that a review of policies both of developing as well as of developed countries could help to put some observations into a perspective that is closer to the Brazilian reality.

Development and biological evaluation of API-ILs based on anti-bacterial and anti-fungal drugs

In recent years Ionic Liquids (ILs) are being applied in life sciences. ILs are being produce with active pharmaceutical drugs (API) as they can reduce polymorphism and drug solubility problems [1] Also ILs are being applied as a drug delivery device in innovative therapies What is appealing in ILs is the ILs building up platform, the counter-ion can be carefully chosen in order to avoid undesirable side effects or to give innovative therapies in which two active ions are paired. This work shows ILs based on ampicillin (an anti-bacterial agent) and ILs based on Amphotericin B. Also we show studies that indicate that ILs based on Ampicillin could reverse resistance in some bacteria. The ILs produced in this work were synthetized by the neutralization method described in Ferraz et. al. [2] Ampicillin anion was combined with the following organic cations 1-ethyl-3-methylimidazolium, [EMIM]; 1-hydroxy-ethyl-3-methylimidazolium, [C2OHMIM]; choline, [cholin]; tetraethylammonium, [TEA]; cetylpyridinium, [C16pyr] and trihexyltetradecylphosphonium, [P6,6,6,14]. Amphotericin B was combined with [C16pyr], [cholin] and 1-metohyethyl-3-methylimidazolium, [C3OMIM]. The ILs-APIs based on ampicillin[2] were tested against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumonia (clinical isolated), as well as on Gram positive Staphylococcus Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis. The arising resistance developed by bacteria to antibiotics is a serious public health threat and needs new and urgent measures. We study the bacterial activity of these compounds against a panel of resistant bacteria (clinical isolated strains): E. coli CTX M9, E. coli TEM CTX M9, E. coli TEM1, E. coli CTX M2, E. coli AmpC Mox2. In this work we demonstrate that is possible to produce ILs from anti-bacterial and anti-fungal compounds. We show here that the new ILs can reverse the bacteria resistance. With the careful choice of the organic cation, it is possible to create important biological and physic-chemical properties. This work also shows that the ion-pair is fundamental in ampicillin mechanism of action.

Toxicology of metals and metalloids

Metal toxicology is one of the oldest areas of study of toxicology and one of the oldest environmental problems. Metals and metalloids are toxic elements at the top of the priority list of hazardous substances of the Agency for Toxic Substances and Disease Registry (ATSDR). However, several gaps of knowledge still exist that are related to their toxicity, mainly concerning the mechanisms of action. This special issue affords the opportunity to bring together the results of nine papers covering several aspects of the toxicology of metals and metalloids in in vitro and in vivo experimental models, as well as in exposed populations.

Portuguese newspapers’ front-page and the coverage of European Cultural Capital: Porto 2001 and Guimarães 2012

Portugal hosted in the last thirteen years, two editions of the event European Cultural Capital; this paper intends to illustrate the coverage that Portuguese newspapers (daily newspapers Público, Diário de Notícias, Correio da Manhã and Jornal de Notícias, a weekly newsmagazine Visão and a weekly newspaper Expresso) made, through referrals in front-page and respective developments within the editions, to each of the events and that allows us to define the main moments that marked each of them, patterns of action, the major players, planning and programming types. The European Cultural Capital project elects, from year to year, cities of different EU member states with the main goal of “contributing to bring together the Europe´s people" (words of Mélina Mercouri, Greek Minister of Culture who, in 1985, proposed the launch of this initiative) and encouraging the elected urban space to present new cultural paradigms. In the genesis of this model is the cultural decentralization’s vector, a possibility to medium-sized cities of funding public works, restoring heritage and promoting themselves in touristic terms, of giving visibility to cities away from cultural and creative industries’ major distribution centers. A crucial factor to achieve this goal is media coverage. This paper outline the information that the Portuguese press ran over the two years that elapsed the latest editions of the European Cultural Capital in Portugal, namely that media coverage have deviated from the disclosure of the events’ schedule to suggest itineraries of visit and little or not even question the role that cities, promoting such initiatives, have as places of innovation in terms of cultural policies, artistic production and innovation, in urban and environmental regeneration, in economic revitalization, in training and creating new artists and new audiences and in boosting the confidence of local communities. The content analysis performed to articles shows how press is essential to the promotion of cities as cultural/touristic destinations as it stimulates consumption among residents and attracts visitors, with the possible dire consequence of turning the cultural journalist into an agent of touristic instead of cultural promotion.

Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies

The very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.

Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.