Electrochemical Reduction as a Powerful Tool to Highlight the Possible Formation of By-Products More Toxic Than Sudan III Dye

The present work describes the electrochemical reduction of the azo dye Sudan III in methanol/0.01 mol l(-1) Bu4NBF4 at applied potential of -1.2V, which promotes 98% discoloration of the commercial sample. The reduction products were analyzed by high performance liquid chromatography, after optimized conditions for 20 aromatic amines with carcinogenic potentiality. The harmful compounds such as: aniline, benzidine, o-toluidine, 2,6-dimethylaniline, 4,4'-oxydianiline, 4,4'-metileno-bis-2-methylaniline and 4-aminobiphenyl are formed after azo bond cleavage. The electrochemical reduction is compared with chemical reduction by using sodium thiosulfate. Our findings illustrates that commercial Sudan III under reductive condition can forms a number of products, which some are known active genotoxins. The technique could be used to mimic important redox reactions in human metabolism or environment, highlighting the possible formation of by-products more toxic than the original dyes.

Straightforward Synthesis of Carbon-Supported Ag Nanoparticles and Their Application for the Oxygen Reduction Reaction

In this paper we report a simple and environmentally friendly synthesis of silver nanoparticles (AgNps) and their activities towards the oxygen reduction reaction (ORR). Ultraviolet spectroscopy (UV-vis) and transmission electron microscopy confirmed the formation of poly(vinyl pyrrolidone)-protected colloidal AgNps through direct reduction of Ag+ by glycerol in alkaline medium at room temperature. For the ORR tests, the AgNps were directly produced onto carbon to yield the Ag/C catalyst. Levich plots revealed the process to occur via 2.7 electrons, suggesting that the carbon support contributes to the ORR. We discuss here possibilities of improving the catalytic properties of the Ag/C for ORR by optimizing the parameters of the synthesis.

Biotransformation of 4-nerolidylcatechol by Heraclides brasiliensis (Lepidoptera: Papilionidae) reduces the toxicity of Piper umbellata (Piperaceae)

Heraclides brasiliensis (Lepidoptera: Papilionidae) larvae feed preferably on Piperaceae, foraging successfully on leaf tissues even though species of this contain high levels of secondary metabolites such as amides and lignans, associated with diverse biological activities including insecticidal properties. Studies examining the metabolism of chemical constituents in Piperaceae by insects are rare. In this study, we characterized the metabolites of 4-nerolidylcatechol (4-NC), the major constituent of Piper umbellata (Piperaceae), and E-2,3-dihydro-3-(3,4-dihydroxyphenyl)farnesoic acid, compounds from fecal material of H. brasiliensis larvae fed a diet containing only P. umbellata leaves. The biotransformed product was also detected in larval and pupal tissues. Moreover, we observed deactivation of the toxicity of P. umbellata leaves against brine shrimp after their metabolism in H. brasiliensis larvae from a LC50 of 523.3 to 3,460.7 mu g/mL. This deactivation is closely associated with the biotransformation of 4-NC to E-2,3-dihydro-3-(3,4-dihydroxyphenyl)farnesoic acid, which showed LC50 of 8.0 and >1,000 mu g/mL, respectively.

Performance and selectivity of PtxSn/C electro-catalysts for ethanol oxidation prepared by reduction with different formic acid concentrations

Carbon supported Pt-Sn catalysts were prepared by reduction of Pt and Sn precursors with formic acid and characterized in terms of structure, morphology and surface properties. The electrocatalytic activity for ethanol oxidation was studied in a direct ethanol fuel cell (DEFC) at 70 degrees C and 90 degrees C. Electrochemical and physico-chemical data indicated that a proper balance of Pt and Sn species in the near surface region was necessary to maximize the reaction rate. The best atomic surface composition, in terms of electrochemical performance, was Pt:Sn 65:35 corresponding to a bulk composition 75:25 namely Pt3Sn1/C. The reaction products of ethanol electro-oxidation in single cell and their distribution as a function of the nature of catalyst were determined. Essentially, acetaldehyde and acetic acid were detected as the main reaction products; whereas, a lower content of CO2 was formed. The selectivity toward acetic acid vs. acetaldehyde increased with the increase of the Sn content and decreased by decreasing the concentration of the reducing agent used in the catalyst preparation. According to the recent literature, these results have been interpreted on the basis of ethanol adsorption characteristics and ligand effects occurring for Sn-rich electrocatalysts. (C) 2012 Elsevier Ltd. All rights reserved.

Effectiveness of a long-term use of a minimalist footwear versus habitual shoe on pain, function and mechanical loads in knee osteoarthritis: a randomized controlled trial

Background: Recent studies have shown an important reduction of joint overload during locomotion in elderly women with knee osteoarthritis (OA) after short- term use of minimalist shoes. Our aim is to investigate the chronic effect of inexpensive and minimalist footwear on the clinical and functional aspects of OA and gait biomechanics of elderly women with knee OA. Methods/Design: Fifty-six elderly women with knee OA grade 2 or 3 (Kellgren and Lawrence) are randomized into blocks and allocated to either the intervention group, which will use flexible, non-heeled shoes-Moleca (R)-for six months for at least six hours daily, or the control group, which could not use these shoes. Neither group is undergoing physical therapy treatment throughout the intervention period. Moleca (R) is a women's double canvas, flexible, flat walking shoe without heels, with a 5-mm anti-slip rubber sole and a 3-mm internal wedge of ethylene vinyl acetate. Both groups will be followed for six months and will be assessed at baseline condition, after three months, and after six months (end of intervention). All the assessments will be performed by a physiotherapist that is blind to the group allocation. The primary outcome is the pain Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score. The secondary outcomes are global WOMAC score; joint stiffness and disability WOMAC scores; knee pain with a visual analogue scale; walking distance in the six-minute walk test; Lequesne score; amount and frequency (number of days) of paracetamol (500 mg) intake over six months; knee adduction moment during gait; global medical assessment score; and global patient auto-assessment score. At baseline, all patients receive a diary to record the hours of daily use of the footwear intervention; every two weeks, the same physiotherapist makes phone calls to all patients in order to verify adherence to treatment. The statistical analysis will be based on intention to treat analysis, as well as general linear models of analysis of variance for repeated measure to detect treatment-time interactions (alpha = 5%). Discussion: This is the first randomized, clinical trial protocol to assess the chronic effect of minimalist footwear on the clinical and functional aspects and gait biomechanics of elderly women with knee osteoarthritis. We expect that the use of Moleca (R) shoes for six months will provide pain relief, reduction of the knee adduction moment when walking, and improve joint function in elderly women with knee OA, and that the treatment, thus, can be considered another inexpensive and easy-to-use option for conservative OA treatment.

The relationship between leaf nitrogen, nitrogen metabolites and herbivory in two species of Nyctaginaceae from the Brazilian Cerrado

Guapira graciliflora and Neea theifera are taxonomically related species of the tribe Pisoneae. Both species are found in the same environment, the Brazilian Cerrado, and therefore, are subjected to similar selective pressures. These species occur in oligotrophic environments, yet contain high concentrations of nitrogen in their leaves. The present study was carried out to investigate the ecological role of nitrogen in herbivory on these species. The differences in the N content, compositions of secondary N-metabolites, mechanical resistance, and water content between their leaves indicate that these species have different adaptations as defense mechanisms. In both species, their high nitrogen content seems to promote herbivory. The presence of secondary nitrogen metabolites does not prevent the species from suffering intense damage by herbivores on their early leaves. The herbivory rates observed were lower for mature leaves of both species than for young leaves. In G. graciliflora, nutritional content and leaf hardness are the most important variables correlated with reduction of herbivory rates, whereas in N. theifera, N compounds are also correlated with herbivory rates. Despite the differences in the strategies of these two species, they exhibit a similar efficiency of protection against natural enemies because their total herbivory rates are similar. The difference in their N defense allocation may imply benefits for survival under Cerrado conditions. We briefly discuss the oligotrophic habitat conditions of the studied plants and possible advantages of their strategies of N accumulation and metabolic uses. (C) 2011 Elsevier B.V. All rights reserved.

Oral antibacterial effect of chlorhexidine treatments and professional prophylaxis in children

Aim: The primary aim of this longitudinal study was to evaluate additional effects of 4-week chlorhexidine digluconate (CHX) gel treatments to control Aggregatibacter actinomycetemcomitans counts in children after professional dental prophylaxis. Porphyromonas gingivalis and Streptococcus mutans counts were also determined to evaluate the secondary effects of anti-plaque treatments on microbial shifts. Methods: Twenty-six children with A. actinomycetemcomitans counts >4 log10/ mL of saliva and/or Quigley-Hein plaque index >3.0 were enrolled in this study. Patients were randomly assigned to groups GI (placebo gel), GII (0.5% CHX gel), GIII (1% CHX gel), and GIV (2% CHX gel). Four sessions of treatment were performed during 4 weeks after a session of professional dental prophylaxis. Real-Time polymerase chain reaction (PCR) was used to determine viable microorganism counts in non-stimulated whole saliva samples collected at baseline, one week, one month and three months after interruption of treatments. Results: A reduction of all bacterial counts was detected after the 3-month follow-up in all groups. Lower counts of P. gingivalis were achieved from 1 week on after treatments. The 2% CHX concentration seemed to contribute to lower A. actinomycetemcomitans levels and increase S. mutans levels. Conclusions: Professional dental prophylaxis was effective to control salivary levels of A. actinomycetemcomitans, P. gingivalis and S. mutans. Additional antimicrobial effects, however, were not observed by the combination of professional dental prophylaxis and 4-week chlorhexidine gel treatments.

Evaluating methods for the isolation of marine-derived fungal strains and production of bioactive secondary metabolites

In the present investigation we evaluate methods for the isolation and growth of marine-derived fungal strains in artificial media for the production of secondary metabolites. Inoculation of marine macroorganisms fragments in Petri dishes proved to be the most convenient procedure for the isolation of the largest number of strains. Among the growth media used, 3% malt extract showed the best result for strains isolation and growth, and yielded the largest number of strains from marine macroorganisms. The percentage of strains isolated using each of the growth media which yielded cytotoxic and/or antibiotic extracts was in the range of 23-35%, regardless of the growth media used. Further investigation of extracts obtained from different marine-derived fungal strains yielded several bioactive secondary metabolites, among which (E)-4-methoxy-5-(3-methoxybut-1-enyl)-6-methyl-2H-pyran-2-one is a new metabolite isolated from the Penicillium paxilli strain Ma(G)K.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation.

Synthetic and mechanistic investigation of new radical processes: reaction of organic azides with group-XIII Lewis acids

Dichloroindium hydride revealed to be a valid alternative to tributyltin hydride for radical reduction of organic (alkyl, aryl, acyl, solfonyl) azides. The new approach entails mild reaction conditions and provides high yields of the corresponding amines and amides, also showing high degrees of selectivity. The system dichloroindium hydride / azides can be utilised in fivemembered ring closures of g-azidonitriles, as a new source of aminyl radicals for the attractive synthesis of interesting amidine compounds in the absence of both toxic reagents and tedious purification procedures. Allylindium dichloride seems a good substitute for dichloroindium hydride for generation of indium centred radicals under photolytic conditions, since it allows allylation of electrophilic azides (e.g. phenylsulfonyl azide) and halogen or ester δ-substituted azides, the latter through a 1,5-H transfer rearrangement mechanism. Evidences of the radical nature of the reactions mechanism were provided by ESR spectroscopy, furthermore the same technique, allowed to discover that the reaction of azides with indium trichloride and other group XIII Lewis acids, in particular gallium trichloride, gives rise to strongly coloured, persistent paramagnetic species, whose structure is consistent with the radical cation of the head-to-tail dimer of the aniline corresponding to the starting azide.

Effects of Resources Exploitation on Water Quality: case studies in Salt Water Intrusion and Acid Mine Drainage

Throughout the world, pressures on water resources are increasing, mainly as a result of human activity. Because of their accessibility, groundwater and surface water are the most used reservoirs. The evaluation of the water quality requires the identification of the interconnections among the water reservoirs, natural landscape features, human activities and aquatic health. This study focuses on the estimation of the water pollution linked to two different environmental issues: salt water intrusion and acid mine drainage related to the exploitation of natural resources. Effects of salt water intrusion occurring in the shallow aquifer north of Ravenna (Italy) was analysed through the study of ion- exchange occurring in the area and its variance throughout the year, applying a depth-specific sampling method. In the study area were identified ion exchange, calcite and dolomite precipitation, and gypsum dissolution and sulphate reduction as the main processes controlling the groundwater composition. High concentrations of arsenic detected only at specific depth indicate its connexion with the organic matter. Acid mine drainage effects related to the tin extraction in the Bolivian Altiplano was studied, on water and sediment matrix. Water contamination results strictly dependent on the seasonal variation, on pH and redox conditions. During the dry season the strong evaporation and scarce water flow lead to low pH values, high concentrations of heavy metals in surface waters and precipitation of secondary minerals along the river, which could be released in oxidizing conditions as demonstrated through the sequential extraction analysis. The increase of the water flow during the wet season lead to an increase of pH values and a decrease in heavy metal concentrations, due to dilution effect and, as e.g. for the iron, to precipitation.

Complementary mass spectrometric techniques for the characterization of the organic fraction in atmospheric aerosols

Aerosol particles are strongly related to climate, air quality, visibility and human health issues. They contribute the largest uncertainty in the assessment of the Earth´s radiative budget, directly by scattering or absorbing solar radiation or indirectly by nucleating cloud droplets. The influence of aerosol particles on cloud related climatic effects essentially depends upon their number concentration, size and chemical composition. A major part of submicron aerosol consists of secondary organic aerosol (SOA) that is formed in the atmosphere by the oxidation of volatile organic compounds. SOA can comprise a highly diverse spectrum of compounds that undergo continuous chemical transformations in the atmosphere.rnThe aim of this work was to obtain insights into the complexity of ambient SOA by the application of advanced mass spectrometric techniques. Therefore, an atmospheric pressure chemical ionization ion trap mass spectrometer (APCI-IT-MS) was applied in the field, facilitating the measurement of ions of the intact molecular organic species. Furthermore, the high measurement frequency provided insights into SOA composition and chemical transformation processes on a high temporal resolution. Within different comprehensive field campaigns, online measurements of particular biogenic organic acids were achieved by combining an online aerosol concentrator with the APCI-IT-MS. A holistic picture of the ambient organic aerosol was obtained through the co-located application of other complementary MS techniques, such as aerosol mass spectrometry (AMS) or filter sampling for the analysis by liquid chromatography / ultrahigh resolution mass spectrometry (LC/UHRMS).rnIn particular, during a summertime field study at the pristine boreal forest station in Hyytiälä, Finland, the partitioning of organic acids between gas and particle phase was quantified, based on the online APCI-IT-MS and AMS measurements. It was found that low volatile compounds reside to a large extent in the gas phase. This observation can be interpreted as a consequence of large aerosol equilibration timescales, which build up due to the continuous production of low volatile compounds in the gas phase and/or a semi-solid phase state of the ambient aerosol. Furthermore, in-situ structural informations of particular compounds were achieved by using the MS/MS mode of the ion trap. The comparison to MS/MS spectra from laboratory generated SOA of specific monoterpene precursors indicated that laboratory SOA barely depicts the complexity of ambient SOA. Moreover, it was shown that the mass spectra of the laboratory SOA more closely resemble the ambient gas phase composition, indicating that the oxidation state of the ambient organic compounds in the particle phase is underestimated by the comparison to laboratory ozonolysis. These observations suggest that the micro-scale processes, such as the chemistry of aerosol aging or the gas-to-particle partitioning, need to be better understood in order to predict SOA concentrations more reliably.rnDuring a field study at the Mt. Kleiner Feldberg, Germany, a slightly different aerosol concentrator / APCI-IT-MS setup made the online analysis of new particle formation possible. During a particular nucleation event, the online mass spectra indicated that organic compounds of approximately 300 Da are main constituents of the bulk aerosol during ambient new particle formation. Co-located filter analysis by LC/UHRMS analysis supported these findings and furthermore allowed to determine the molecular formulas of the involved organic compounds. The unambiguous identification of several oxidized C 15 compounds indicated that oxidation products of sesquiterpenes can be important compounds for the initial formation and subsequent growth of atmospheric nanoparticles.rnThe LC/UHRMS analysis furthermore revealed that considerable amounts of organosulfates and nitrooxy organosulfates were detected on the filter samples. Indeed, it was found that several nitrooxy organosulfate related APCI-IT-MS mass traces were simultaneously enhanced. Concurrent particle phase ion chromatography and AMS measurements indicated a strong bias between inorganic sulfate and total sulfate concentrations, supporting the assumption that substantial amounts of sulfate was bonded to organic molecules.rnFinally, the comprehensive chemical analysis of the aerosol composition was compared to the hygroscopicity parameter kappa, which was derived from cloud condensation nuclei (CCN) measurements. Simultaneously, organic aerosol aging was observed by the evolution of a ratio between a second and a first generation biogenic oxidation product. It was found that this aging proxy positively correlates with increasing hygroscopicity. Moreover, it was observed that the bonding of sulfate to organic molecules leads to a significant reduction of kappa, compared to an internal mixture of the same mass fractions of purely inorganic sulfate and organic molecules. Concluding, it has been shown within this thesis that the application of modern mass spectrometric techniques allows for detailed insights into chemical and physico-chemical processes of atmospheric aerosols.rn

Clazosentan: prevention of cerebral vasospasm and the potential to overcome infarction

Cerebral vasospasm is a common complication occurring after aneurysmal subarachnoid hemorrhage (SAH). It is recognized as a leading preventable cause of morbidity and mortality in this patient group, but its management is challenging, and new treatments are needed. Clazosentan is an endothelin receptor antagonist designed to prevent endothelin-mediated cerebral vasospasm. Vajkoczy et al. (Neurosurg 103:9-17, 2005) initially demonstrated that clazosentan reduced moderate/severe angiographically proven vasospasm by 55% relative to placebo. These findings led to the initiation of the CONSCIOUS trial program to further examine the efficacy and safety of clazosentan in reducing angiographic vasospasm and improving clinical outcome after aneurysmal SAH. In the first of these studies, CONSCIOUS-1, 413 patients were randomized to placebo or clazosentan 1, 5 or 15 mg/h. Clazosentan reduced angiographic vasospasm dose-dependently relative to placebo with a maximum risk reduction of 65% with the highest dose. Despite this, there was no benefit of clazosentan on the secondary protocol-defined morbidity/mortality endpoint; however, additional post-hoc and modified endpoint analyses provided some evidence for a potential clinical benefit. Two additional large-scale studies (CONSCIOUS-2 and CONSCIOUS-3) are now underway to further investigate the potential of clazosentan to improve long-term clinical outcome.

[Management of transient ischemic attack (TIA) and acute stroke]

Patients with a transient ischemic attack and an acute stroke need urgent investigations and therapy in a stroke unit. Immediate investigation of the etiology and early secondary prevention measures reduce the likelihood of recurrent and other vascular events. In selected stroke patients intravenous thrombolysis and/or endovascular therapies lead to a significant reduction of long term disabilities.

Gerbu adjuvant modulates the immune response and thus the course of infection in C56BL/6 mice immunised with Echinococcus multilocularis rec14-3-3 protein

Vaccination with Echinococcus multilocularis 14-3-3 protein can protect mice against primary E. multilocularis infection. The present study investigated the efficacy and efficiency of the adjuvant muramyl dipeptide Gerbu, alone or together with recombinant 14-3-3 protein, to modulate the course of secondary E. multilocularis infection in C56BL/6 mice. The application of Gerbu alone already resulted in a parasite weight reduction when compared with infected control mice, while rec14-3-3 did not add to this effect. Immunological parameters were concurrently assessed with a mixed cell reaction including bone marrow-derived dendritic cells (BMDCs) together with lymph node cells from mice with or without immunisation and/or infection. While mice having received Gerbu adjuvant were found to highly proliferate in response to co-cultivation with 14-3-3-stimulated bone marrow dendritic cells, a sensitisation of BMDCs with vesicle fluid (VF) antigen lead to a striking decrease of the lymphoproliferative response in comparison to that of control mice, raising the hypothesis that immunosuppressive components may be part of this VF-antigen. Anti-14-3-3 antibody production was only found in those mice that had been previously 14-3-3-immunised, whereas all other only-infected mice failed to produce such antibodies. Conclusively, Gerbu adjuvant appears to directly generate a non-specific immune response that contributes to the control of the metacestode growth, putatively in association with a BMDC activity suppressed by components of the VF-antigen.