921 resultados para hepato-biliary toxicity marker


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The Municipal Station of Americana, SP, Brazil, treats a volume of 400 l s-1 of effluent, of domestic and textile origin, and produces about 20 t of sludge per day. The plant horseradish, which contains high amount of peroxidases, was able to decolorize this effluent in 2 h and the solid waste in 2 days, at concentrations of 10 and 50%, respectively. However, there was an increase in the toxicity for the bioassays with Hydra attenuatta, Selenastrum capricornutum and lettuce seeds, indicating formation of more toxic substances. Since horseradish showed the ability to decolorize these residues, it can be used as pre-treatment resulting in a sludge of less complex composition.

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The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event

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In recent years, one important objective of cardiovascular research has been to find new markers that would improve the risk stratification and diagnosis of patients presenting with symptoms of acute coronary syndrome (ACS). Pregnancy-associated plasma protein A (PAPP-A) is a large metalloproteinase involved in insulin-like growth factor signalling. It is expressed in various tissues and seems to be involved in many physiological and pathological processes, such as folliculogenesis, bone formation, wound healing, pregnancy and atherosclerosis. The aim of this thesis was to investigate PAPP-A in ACS patients. Circulating concentrations of PAPP-A had been previously shown to be elevated in ACS. In this study it was revealed that the form of PAPP-A causing this elevation was the free noncomplexed PAPP-A. Thus, the form of PAPP-A in the circulation of ACS patients differed from the complexed PAPP-A form abundantly present in the circulation during pregnancy. A point-of-care method based on time-resolved immunofluorometric assays was developed, which enabled the rapid detection of free PAPP-A. The method was found to perform well with serum and heparin plasma samples as well as with heparinized whole blood samples. With this method the concentrations of free PAPP-A in healthy individuals were shown to be negligible. When the clinical performance of the method was evaluated with serum samples from ACS patients, it was shown that the free PAPP-A concentration in the admission sample was an independent predictor of myocardial infarction and death. Moreover, as a prognostic marker, free PAPP-A was revealed to be superior to total PAPPA, i.e. the combination of free and complexed PAPP-A, which has been measured by the other groups in this field. As heparin products are widely used as medication in ACS patients, the effect of heparin products on free PAPP-A molecule and circulating concentrations were also investigated in this study. It was shown that intravenous administration of low molecular weight or unfractionated heparin elicits a rapid release of free PAPP-A into the circulation in haemodialysis patients and patients undergoing angiography. Moreover, the interaction between PAPP-A and heparin was confirmed in gel filtration studies. Importantly, the patients included in the clinical evaluation of the free PAPP-A detection method developed had not received any heparin product medication before the admission sample and thus the results were not affected by the heparin effect. In conclusion, free PAPP-A was identified as a novel marker associated with ACS. The point-of-care methods developed enable rapid detection of this molecule which predicts adverse outcome when measured in the admission sample of ACS patients. However, the effect revealed of heparin products on circulating PAPP-A concentrations should be acknowledged when further studies are conducted related to free or total PAPP-A in ACS.

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The phytochemical investigation of Herissantia crispa led to the isolation of seven compounds, identified as: sitosterol 3-O-β-D-glucopyranoside, stigmasterol 3-O-β-D-glucopyranoside, 3,5,7,4'-tetrahydroxyflavone (kaempferol), 3,5,7,3',4'-pentahydroxyflavone (quercetin), unpublished in the genus Herissantia, besides β-sitosterol, kaempferol 3-O-β-D-(6''-E-p-coumaroil) (tiliroside) glucopyranoside and kaempferol 3,7-di-O-α-L-ramnopyranoside (lespedin), described for the first time in the species. The structural determination of the compounds was made by means of spectroscopy methods such as Infrared Spectroscopy, ¹H and 13C Nuclear Magnetic Resonance, with the aid of two dimensional techniques, and by comparison with literature data. The toxicity activity of the MeOH extract and lespedin on Artemia salina Leach. was also carried out.

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Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

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Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

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Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

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Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

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Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

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Aloysia gratissima (Gill. et Hook) Tronc. (Verbenaceae) is native to South America with folk therapeutic applications for a wide range of diseases. The polyphenolic and carotenoid profile, toxicity, and antioxidant activity of aqueous extract of Aloysia gratissima were investigated. HPLC analyses showed high amounts of ferulic acid, trans-cinnamic acid and p-coumaric acid, and also trans-β- carotene and lutein which fluctuated throughout the seasons. Furthermore, the extract investigated not only exerted antioxidant activity but also inhibited lipid peroxidation. Toxicity was achieved only at the highest dose tested. Therefore, A. gratissima is a potential species for medicinal purposes.

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Pfaffic acid, a marker of Hebanthe eriantha (Brazilian ginseng), was first isolated in 1983 but is not yet commercially available. This lack of availability compromises the quality control of this plant and its derivatives. This paper proposes a process for pfaffic acid isolation from roots of H. eriantha at a purity suitable for analytical purposes. The steps involved in this process included extraction, hydrolysis, fractionation and purification by preparative HPLC. This process led to isolation of pfaffic acid with a chromatographic purity of 98.5% in a 0.25% yield from dried roots of H. eriantha; this yield is more than forty times higher than that of the current method in the literature.

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Extracts of six lichen species collected from Brazil and Antarctica were investigated for their potential toxicity and radical-scavenging properties. The composition of the extracts was investigated using TLC and NMR, leading to identification of atranorin (1), along with salazinic (2), barbatic (3), α-alectoronic (4), α-collatolic (5), cryptochlorophaeic (6), caperatic (7), lobaric (8), and protolichesterinic (9) acids. All acetone extracts were evaluated for their 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability and subjected to Artemia salina bioassay. The free-radical-scavenging activities of each extract (100 µg) ranged from 8.9 ± 0.1% to 38.7 ± 2.5% and the EC50 values ranged from 0.24 ± 2.10 to 3.54 ± 0.28 mg mL-1, while the toxicity of the extracts against A. salina were low (151.0 to >600 µg mL-1).

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Chromium toxicity affects redox reactions within plant cells, generating detrimental reactive oxygen species. Glutathione is an antioxidant peptide and also a substrate for the production of phytochelatins, which are chelating peptides reported to mitigate Cr3+ toxicity in plants. In this study, Brachiaria brizantha (B. brizantha) and Brachiaria ruziziensis (B. ruziziensis) seedlings were evaluated for physiological responses and glutathione production following the addition of zero or 5 mg L-1 Cr3+ to the nutrient solution. Glutathione levels were determined by colorimetric analysis at 412 nm using 5,5'-dithio-bis(2-nitrobenzoic acid) as a chromophore reagent and recovery with glutathione reductase (with evaluations at days 10 and 20 of continuous growth). The assessments were carried out in a completely randomized design with 2 authentic replications, and arranged in a 23 factorial. Cr3+ caused an average increase of 0.76 mg g-1 in the initial glutathione content. However, by day 20 there was an average reduction of 3.63 mg g-1. Chromium-affected physiological detrimental responses, albeit detected in both species, were less-pronounced in B. ruziziensis, along with a much higher level of glutathione. This study indicates that B. ruziziensis has a greater tolerance for chromium toxicity than B. brizantha, and that glutathione is likely to be involved in the mitigation of chromium stress in B. ruziziensis.

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The gene Pi-ar confers resistance to Pyricularia grisea race IB-45 in a somaclone derived from immature panicles of the susceptible rice (Oryza sativa) cultivar Araguaia. RAPD technique was used to identify molecular markers linked to this gene utilizing bulked segregant analysis. Initially, the two parental DNAs from the resistant donor SC09 and 'Araguaia' were analyzed using random primers. Of the 240 primers tested, 203 produced amplification products. The two parental DNAs along with the resistant and susceptible bulks of F2 population were screened using 48 primers that differentiated resistant and susceptible parents. Even though eight primers differentiated the resistant bulk from the susceptible bulk, as well as somaclone SC09 and 'Araguaia', only one primer, OPC02 ('GTGAGGCGTC'), was found to be tightly linked (1.7cM) to the resistance gene of somaclone SC09.