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71.
The aim of this work was to assess the capacities of some ·NO-donors to release ·NO, and consequently NOx in aerobic medium, or to give peroxynitrite. The method was based on the differential reactivity of serotonin (5-HT) with either NOx or peroxynitrite, leading in phosphate-buffered solutions to 4-nitroso- and 4-nitro-5-HT formation, respectively. Yields and formation rates of 5-HT derivatives with ·NO-donor were compared to those obtained with authentic ·NO or peroxynitrite in similar conditions. Aside from the capacity of diazenium diolates (SPER/NO and DEA/NO) to release ·NO spontaneously, converting 5-HT exclusively to 4-nitroso-5-HT, all other ·NO donors must undergo redox reactions to produce ·NO. S-nitrosoglutathione (GSNO) and sodium nitroprus-side (SNP) modified 5-HT only in the presence of Cu2+, GSNO yielding 6 times more 4-nitroso-5-HT than SNP. Furthermore, in the presence of Cu+, the yield of ·NO-release from GSNO was 45%. The molsidomine metabolite (SIN-1), which was presumed to release both ·NO and O2/·- at pH 7.4, reacted with 5-HT differently, depending on the presence of reductant or oxidant. Under aerobic conditions, SIN-1 acted predominantly as a 5-HT oxidant and also as a poor ·NO and peroxynitrite donor (15% yield of ·NO-release and 14 % yield of peroxynitrite formation). The strong oxidant Cu2+, even in the presence of air oxygen, accelerated oxidation and increased ·NO release from SIN-1 up to 86%. Only a small part of SIN-1 gave simultaneously ·NO and O2/·- able to link together to give peroxynitrite, but other oxidants could enhance ·NO release from SIN-1. 相似文献
72.
Subjects enrolled in studies are not always screened for routine habits such as smoking. Personal history is not always reliable and therefore an objective biomarker is necessary to screen for smokers. The objectives of this article were to review the metabolism of nicotine and other metabolic considerations associated with smoking; to review some of the routine methods used to assess exposure to nicotine-containing products; to revisit cotinine breakpoints utilized to distinguish smokers from non-smokers during screening for clinical trials; to assess the utility of screening questions regarding smoking practices; and to recommend standards for clinical pharmacology studies. The results indicated that cotinine levels serve as a useful biomarker of tobacco exposure; racial issues may be clinically relevant in determining smoking status; cessation of smoking should occur at least 14 days prior to the start of the study; adverse effects from nicotine withdrawal such as craving, hunger and weight gain may persist for more than 6 months; potential metabolic interactions via cytochrome P2A6 and P1A2 need to be considered when designing a study; and the use of a single calibrator as a breakpoint is acceptable if a categorical outcome such as 'smoker' versus 'non-smoker' is desired. Nicotine from food products is not expected to impact assay sensitivity or to be clinically relevant; a serum cotinine concentration of 10 ng ml?1 be employed as a breakpoint for non-smokers versus smokers; other non-invasive alternatives are collection of urine, saliva, or hair (with suggested breakpoints of 200 ng ml?1, 5 ng ml?1 and 0.3 ng mg?1, respectively; screening questions be accompanied by testing for cotinine; and the inclusion of smokers in studies should be considered once the impact of smoking on the targeted population is understood. 相似文献
73.
74.
Beatrice Sbriscia-Fioretti Cristina Berchio David Freedberg Vittorio Gallese Maria Alessandra Umiltà 《PloS one》2013,8(10)
The aim of this study was to test the involvement of sensorimotor cortical circuits during the beholding of the static consequences of hand gestures devoid of any meaning.In order to verify this hypothesis we performed an EEG experiment presenting to participants images of abstract works of art with marked traces of brushstrokes. The EEG data were analyzed by using Event Related Potentials (ERPs). We aimed to demonstrate a direct involvement of sensorimotor cortical circuits during the beholding of these selected works of abstract art. The stimuli consisted of three different abstract black and white paintings by Franz Kline. Results verified our experimental hypothesis showing the activation of premotor and motor cortical areas during stimuli observation. In addition, abstract works of art observation elicited the activation of reward-related orbitofrontal areas, and cognitive categorization-related prefrontal areas. The cortical sensorimotor activation is a fundamental neurophysiological demonstration of the direct involvement of the cortical motor system in perception of static meaningless images belonging to abstract art. These results support the role of embodied simulation of artist’s gestures in the perception of works of art. 相似文献
75.
Benjamin Steeb Beatrice Claudi Neil A. Burton Petra Tienz Alexander Schmidt Hesso Farhan Alain Mazé Dirk Bumann 《PLoS pathogens》2013,9(4)
Pathogen access to host nutrients in infected tissues is fundamental for pathogen growth and virulence, disease progression, and infection control. However, our understanding of this crucial process is still rather limited because of experimental and conceptual challenges. Here, we used proteomics, microbial genetics, competitive infections, and computational approaches to obtain a comprehensive overview of Salmonella nutrition and growth in a mouse typhoid fever model. The data revealed that Salmonella accessed an unexpectedly diverse set of at least 31 different host nutrients in infected tissues but the individual nutrients were available in only scarce amounts. Salmonella adapted to this situation by expressing versatile catabolic pathways to simultaneously exploit multiple host nutrients. A genome-scale computational model of Salmonella in vivo metabolism based on these data was fully consistent with independent large-scale experimental data on Salmonella enzyme quantities, and correctly predicted 92% of 738 reported experimental mutant virulence phenotypes, suggesting that our analysis provided a comprehensive overview of host nutrient supply, Salmonella metabolism, and Salmonella growth during infection. Comparison of metabolic networks of other pathogens suggested that complex host/pathogen nutritional interfaces are a common feature underlying many infectious diseases. 相似文献
76.
Innocent Safeukui Pierre A. Buffet Sylvie Perrot Alain Sauvanet Beatrice Aussilhou Safi Dokmak Anne Couvelard Dominique Cazals Hatem Narla Mohandas Peter H. David Odile Mercereau-Puijalon Geneviève Milon 《PloS one》2013,8(3)
Ex vivo perfusion of human spleens revealed innate retention of numerous cultured Plasmodium falciparum ring-infected red blood cells (ring-iRBCs). Ring-iRBC retention was confirmed by a microsphiltration device, a microbead-based technology that mimics the mechanical filtering function of the human spleen. However, the cellular alterations underpinning this retention remain unclear. Here, we use ImageStream technology to analyze infected RBCs’ morphology and cell dimensions before and after fractionation with microsphiltration. Compared to fresh normal RBCs, the mean cell membrane surface area loss of trophozoite-iRBCs, ring-iRBCs and uninfected co-cultured RBCs (uRBCs) was 14.2% (range: 8.3–21.9%), 9.6% (7.3–12.2%) and 3.7% (0–8.4), respectively. Microsphilters retained 100%, ∼50% and 4% of trophozoite-iRBCs, ring-iRBCs and uRBCs, respectively. Retained ring-iRBCs display reduced surface area values (estimated mean, range: 17%, 15–18%), similar to the previously shown threshold of surface-deficient RBCs retention in the human spleen (surface area loss: >18%). By contrast, ring-iRBCs that successfully traversed microsphilters had minimal surface area loss and normal sphericity, suggesting that these parameters are determinants of their retention. To confirm this hypothesis, fresh normal RBCs were exposed to lysophosphatidylcholine to induce a controlled loss of surface area. This resulted in a dose-dependent retention in microsphilters, with complete retention occurring for RBCs displaying >14% surface area loss. Taken together, these data demonstrate that surface area loss and resultant increased sphericity drive ring-iRBC retention in microsphilters, and contribute to splenic entrapment of a subpopulation of ring-iRBCs. These findings trigger more interest in malaria research fields, including modeling of infection kinetics, estimation of parasite load, and analysis of risk factors for severe clinical forms. The determination of the threshold of splenic retention of ring-iRBCs has significant implications for diagnosis (spleen functionality) and drug treatment (screening of adjuvant therapy targeting ring-iRBCs). 相似文献
77.
Laetitia Aerts Marie-ève Hamelin Chantal Rhéaume Sophie Lavigne Christian Couture WooJin Kim Delia Susan-Resiga Annik Prat Nabil G. Seidah Nathalie Vergnolle Beatrice Riteau Guy Boivin 《PloS one》2013,8(8)
Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections. 相似文献
78.
Marie Josephe Amiot Beatrice Romier Thi-Mai Anh Dao Raphaelle Fanciullino Joseph Ciccolini Remy Burcelin Laurent Pechere Claude Emond Jean-François Savouret Eric Seree 《Biochimie》2013
We have developed an innovative soluble galenic form to overcome the low absorption of trans-Resveratrol (t-Res) as a dry powder. We present here data on pharmacokinetics, bioavailability, and toxicity of t-Res in human volunteers treated with this soluble form, plus additional data on biological effects in rodents. Fifteen healthy volunteers of both sexes received 40 mg of t-Res in two forms, the soluble formulation (caplets) and the original powder (capsules), in a crossover design. Blood samples were collected at 15 min, 30 min, and every hour for 5 h. Plasma concentrations of t-Res and its metabolites were analyzed by liquid chromatography and mass spectrometry. The single dose (40 mg) of the soluble t-Res was well absorbed and elicited biologically efficient blood levels (0.1–6 μM) for several hours, despite metabolization into glucuronide and sulfate conjugates coupled to renal elimination. In contrast, t-Res administered as a dry powder barely elicited efficient blood levels for a short duration. The new formulation led to 8.8-fold higher t-Res levels in plasma versus the powder. t-Res metabolism was not modified and neither intolerance nor toxicity were observed during the study and the following week. The soluble formulation elicited a robust anti-inflammatory effect in various tissues of mice fed a high-fat diet, while dry powder t-Res was almost inactive. Our data suggest that significant improvements in t-Res bioavailability and efficiency can be obtained by this soluble galenic form, also allowing lower doses. The use of t-Res in human therapy is thus greatly facilitated and the toxicity risk is reduced. 相似文献
79.
Pedro H. C. Pereira João L. L. Feitosa Diego V. Medeiros Beatrice P. Ferreira 《Acta ethologica》2013,16(1):53-56
Fishes associated in schools acquire adaptive advantages by grouping together, e.g., access to a larger variety of food resources, foraging sites, and protection against potential predators. This work presents the first record of a feeding association between the bucktooth parrotfish, Sparisoma radians and the sailor’s grunt Haemulon parra, on Tamandaré reefs, Southwestern Atlantic. Through this association, S. radians gained access to otherwise unavailable food resources to be found inside territorial damselfish domain, thus characterizing an event of foraging facilitation. 相似文献
80.
Donatella Camerino Paul Maurice Conway Samantha Sartori Paolo Campanini Madeleine Estryn‐Béhar Beatrice Isabella Johanna Maria van der Heijden 《Chronobiology international》2013,30(2-3):425-442
Satisfactory work ability is sustained and promoted by good physical and mental health and by favorable working conditions. This study examined whether favorable and rewarding work‐related factors increased the work ability among European nurses. The study sample was drawn from the Nurses' Early Exit Study and consisted of 7,516 nursing staff from seven European countries working in state‐owned and private hospitals. In all, 10.8% were day, 4.2% were permanent night, 20.9% were shift without night shift, and 64.1% were shift workers with night shifts. Participants were administered a composite questionnaire at baseline (Time 0) and 1 yr later (Time 1). The Work Ability Index (WAI) at Time 1 was used as the outcome measure, while work schedule, sleep, rewards (esteem and career), satisfaction with pay, work involvement and motivation, and satisfaction with working hours at Time 0 were included as potential determinants of work ability. Univariate and multivariate analyses were conducted after adjusting for a number of confounders (i.e., country, age, sex, type of employment, family status, and other job opportunities in the same area). Work schedule was not related to Time 1 changes in WAI. Higher sleep quality and quantity and more favorable psychosocial factors significantly increased work ability levels. Higher sleep quality and quantity did not mediate the effect of work schedule on work ability. No relevant interaction effects on work ability were observed between work schedule and the other factors considered at Time 0. As a whole, sleep and satisfaction with working time were gradually reduced from day work to permanent night work. However, scores on work involvement, motivation, and satisfaction with pay and rewards were the highest in permanent night workers and the lowest in rotating shift workers that included night shifts. 相似文献