895 resultados para Wnt-3a


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The synthesis of two new spirostanic analogs of the natural occurring brassinosteroid 6-desoxocastasterone (1) is described. The scheme consists in the formation and elimination of tigogenin mesylate followed by catalytic dihydroxylation of the resulting D2-steroid (3) and acetylation of the 2a, 3a-diol introduced.Treatment diacetate (5) with NaNO2/BF3.Et2O and chromatography in alumina led to a 23-keto (6) which on reduction produced the 23S alcohol (8) as major product. Saponification of the 2a, 3a-diacetoxy-23-keto compound (6) and the 2a,3a-diacetoxy-23-hydroxy compound (8) led to the spirobrasinosteroids (7) and (9).13C NMR and ¹H RMN characteristics derived from substitution at C23 are briefly discussed.

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Aquest treball és la culminació de les pràctiques realitzades al sincrotró ALBA. Situat a Cerdanyola del Vallès, ALBA és un accelerador de 3a generació que permet emmagatzemar un feix d'electrons confinat de fins a 400 mA a 3GeV d'energia, amb l'objectiu d'obtenir llum a partir dels girs provocats al feix. Els sincrotrons moderns com el d'ALBA, el que pretenen és aconseguir un major control i estabilitat de la llum. Per aconseguir-ho, cal que el feix d'electrons que creen la llum estigui controlat al màxim i la seva òrbita sigui estable. Amb aquest objectiu els sincrotrons estant implementant sistemes de Fast Orbit FeedBack (FOFB) o sistemes realimentats de correcció ràpida de l'òrbita, per realitzar correccions d'almenys 100Hz que estabilitzin el feix d'electrons amb menys d'un 10% de l'amplada del feix (5-10μm). El treball exposa el desenvolupament d'una part del sistema de correcció ràpida de l'òrbita dels electrons (FOFB) que s'està duent a terme al sincrotró ALBA. Concretament, s’han revisat els estudis previs realitzats durant la fase de disseny del sincrotró, s’han recalculat funcions de transferència i retards de tots els elements involucrats al sistema. També s’han realitzat simulacions per confirmar la viabilitat del sistema amb les noves dades i finalment s’ha desenvolupat part de la unitat de control determinant el Hardware i s'ha adquirit dades que permetran analitzar el soroll de l'òrbita que en futurs treballs determinaran millor l'algorisme de la unitat de control.

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Mixtures of α-Santonin and various solvents were irradiated by either high or low pressure mercury lamps. The photochemical reactions afforded lumisantonin (11) (76% in acetonitrile), (3S,3aS,9bS)-3,6,6-trimethyl-3,3a,4,5-tetrahydronafto[1,2-b]furan-2,7(6H,9bH)dione (12) (100% in acetonitrile), 10α-acetoxy-3-oxo-1,7αH,6,11βH-guaia-4-en-6,12-olide (8) (26% in acetic acid), 10α-hydroxy-3-oxo-1,7αH,6,11βH-guaia-4-en-6,12-olide (10) (32%) and (E)-3-((3S,3aS,7aS)-3-methyl-2-oxo-6-(propan-2-ylidene)hexahydrobenzofuran-7-(7aH)-ylidene)propanoic acid (9) (44%) (in water/ acetic acid 1:1, v/v). Lactone 12 was also prepared by irradiation of lumisantonin in diethyl ether. Lactones 8 and 10 were converted, respectively, into the 10α-acetoxy-3β-hydroxy-1,7αH,6,11βH-guaia-4-en-6,12-olide (13) (87%) and 3β,10α-dihydroxy-1,7αH,6,11βH-guaia-4-en-6,12-olide (14) (75%) by sodium borohydride reduction. The effects of the compounds on the development of radicle of Sorghum bicolor and Cucumis sativus were evaluated.

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Static electric dipole polarizabilities and first hyperpolarizabilites have been calculated for the title molecules and their 3' and 4'-nitro derivatives at ab-initio Hartree- Fock/6-31G(d, p) level. The influence of the pivotal p vacant 3A elements (B, Al or Ga) substitution on the electrical properties of these molecules is detailed. The axial vector components of the first hyperpolarizabilities β(0) of the push-pull 4'-nitro derivatives, -18.2×10-32 esu (B), -21.1×10-32 esu (Al) and -20.8×10-32 esu (Ga) are calculated to be as much as fourfold larger then that calculated for the p-nitroaniline, a reference organic molecule for comparison for this type of molecular property.

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A new series of 5-benzylidene-2-[(pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 4a-l have been synthesized. These compounds were designed by a molecular hybridization approach. 2-[(Pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 3a-d were also obtained and used as intermediates to give the target compounds. The in vitro antimicrobial and cytotoxic activities were evaluated for both series. The intermediate 3b showed considerable antibiotic activity against B. subtilis and C. albicans. In the cytotoxic activity compounds 3b (IC50= 4.25 ± 0.36 µg/mL) and 4l (IC50= 1.38 ± 0.04 µg/mL) were effective for inhibition of human erythromyeloblastoid leukemia (K-562) and human lung carcinoma (NCI-H292) cell lines, respectively.

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The chemical composition of Spathelia excelsa (Krause) R. S. Cowan & Brizicky was investigated and the limonoids harrisonin (1) and deacetylspathelin (2), alkaloids folinin and casimiroin mixture (3a, b), plus a further casimiroin (3b) were identified in methanol extract from root. The CH2Cl2 extract from the rachis yielded protolimonoid 3β-angeloyl-21,24-epoxy-7α,21α,23α,25-tetrahydroxy-4α,4β,8β,10β-tetramethyl-25-dimethyl-14,18-cyclo-5α,13α,14α,17α-cholestane (4), and methanol extract, the limonoids limonin diosphenol (5) and perforatin (6), as well as the chromone biflorin (7). Harrisonin and biflorin were isolated for the first time in this genus. On the antifungal assay against witches' broom (Moniliophthoraperniciosa) compound 3b was found to be active.

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Wheat (Triticum aestivum) powdery mildew, caused by the biotrophic fungus Blumeria graminis f. sp. tritici, is one of the most severe foliar diseases attacking this crop, reducing grain yields by 10% to 62% in Brazil. The disease can be controlled by genetic resistance of the host, but the pathogen has physiological specialization, which enables it to infect wheat cultivars that have remained resistant for years. The objective of this work was to evaluate the variability of pathogenic strains of B. graminis f. sp. tritici collected in Brazil and the effectiveness of wheat resistance genes to powdery mildew in the 2003 crop season. Plants of a differential series were inoculated with each monopustular isolate. Thirty-one combinations of effective and ineffective resistance genes were identified. Only the gene Pm4a+... remained totally effective to all isolates, and gene Pm6 was highly effective (below 10% of susceptibility), whereas genes Pm3a and Pm8 were totally ineffective (susceptible to all isolates). Genes Pm3c, D1, and D2 showed low effectiveness (above 50% of susceptibility), and genes Pm1, 2, 4a, 1+?, and 2+Mld had mean effective results to most strains (susceptibility between 10% and 49%). The virulence formula Pm1, 3c, 4a, 6, 1+?, 2+Mld, 4a+..., D2 (effective genes) / 2, 3a, 8, D1 (ineffective genes) was most frequently found, accounting for 15% of the occurrences. The most frequent number of ineffective genes was seven, ranging from three to ten.

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The present elaboration is a "previous note" about two watercourses, Maria Rodrigues and Baguaçú, belonging to Hydrografic System of the Cananeas Lagoon Region in the Southern Part of it he Coast of the Estado de São Paulo, Brazil, which is the objete of our physical and chemical researches. It is based on the first results obtained from our contact with that region, ttfie studies of which are being continued and will still have to confirm or not the previous conclusions, which we are presenting in this "provisional paper". We studied the Maria Rodrigues and the Baguacu under the discussion whether they are to be clasified as a river in the poper sense ot the word or waUer-courses of any other origin. For this purpose we established observatory-stations along their whole course where we collected quantities of water to be analised. The data included in the table nº 1 and 2 refer to the physical and chemical properties of these portions of water. These physical and chemical properties were discussed and compared one with the other according to the observatory-stations, at the same moment and the tide predominating on that occasion. The physical and chemical datas were obtained according to the norms recommended by the Conseil International permanent pour l'Exploration de la Mer, Copenhague. We also presented a sketch of both; we described their relations with regard to the Mar de Cananéia; we inserted comprehensible histograms of the distribution of the observatory-stations, each of them with the respective indices, and at last we tried to correlate the occurrence of the "plancton" with the physical and chemical properties of water as well in the Maria Rodrigues as in the Baguacú. From these researches result the following previous conclusions: 1 - By the data obtained up to now nothing could be formulated as to a cyclical or "seasonal" aspect. 2 - By the comparison of the phenomena which present the rivers in the proper sense of the word and those observed in the Maria Rodrigues and the Baguacú, we are convinced that both are water-courses of the classical type "marigot,". 3 - Their channels are maintained open by the effect of the tide and, more perphaps, by the infiltration-water deriving from the underground-water level owing to the type of the soil of that region, which in mean shows an elevation of 2-4 meters over sea-level. 4 - From tables 1 and 2 and histograms 2 and 3 we stated that the water, not only of the Maria Rodrigues but also of the Baguacú, conserve more or less the same physical and chemical properties, provided that: 1) the localities to be compared are the mouths or equidistant points from them in the lower course, and 2) the moment and tide must be the same. Tables 3a and 3b show sufficiently this supposition.

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The natural occurrence of Pseudomonas syringae pv. tabaci causing leaf spot symptoms in papaya seedlings is reported. The pathogen was identified through biochemical, physiological, serological, and molecular assays and artificial inoculations in papaya plants. It was also shown that the strains were pathogenic to bean and tobacco plants. The restriction patterns obtained with Afa I, Alu I, Dde I, Hae III, Hpa II, Hinf I, Sau 3A I and Taq I of the PCR-RFLP of 16S-23S DNAr were identical to the P. s. pv. tabaci patterns. Primers corresponding to hrpL gene of P. syringae were also tested and the results grouped the papaya strains with P s. pv. tabaci. Bacterial strains were deposited at Coleção de Culturas IBSBF, Instituto Biológico, Campinas, Brazil, under access numbers 1687 and 1822.

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Chondrogenesis is a co-ordinated differentiation process in which mesenchymal cells condensate, differentiate into chondrocytes and begin to secrete molecules that form the extracellular matrix. It is regulated in a spatio-temporal manner by cellular interactions and growth and differentiation factors that modulate cellular signalling pathways and transcription of specific genes. Moreover, post-transcriptional regulation by microRNAs (miRNAs) has appeared to play a central role in diverse biological processes, but their role in skeletal development is not fully understood. Mesenchymal stromal cells (MSCs) are multipotent cells present in a variety of adult tissues, including bone marrow and adipose tissue. They can be isolated, expanded and, under defined conditions, induced to differentiate into multiple cell lineages including chondrocytes, osteoblasts and adipocytes in vitro and in vivo. Owing to their intrinsic capability to self-renew and differentiate into functional cell types, MSCs provide a promising source for cell-based therapeutic strategies for various degenerative diseases, such as osteoarthritis (OA). Due to the potential therapeutic applications, it is of importance to better understand the MSC biology and the regulatory mechanisms of their differentiation. In this study, an in vitro assay for chondrogenic differentiation of mouse MSCs (mMSCs) was developed for the screening of various factors for their chondrogenic potential. Conditions were optimized for pellet cultures by inducing mMSC with different bone morphogenetic proteins (BMPs) that were selected based on their known chondrogenic relevance. Characterization of the surface epitope profile, differentiation capacity and molecular signature of mMSCs illustrated the importance of cell population composition and the interaction between different populations in the cell fate determination and differentiation of MSCs. Regulation of Wnt signalling activity by Wnt antagonist sFRP-1 was elucidated as a potential modulator of lineage commitment. Delta-like 1 (dlk1), a factor regulating adipogenesis and osteogenesis, was shown to exhibit stage-specific expression during embryonic chondrogenesis and identified as a novel regulator of chondrogenesis, possibly through mediating the effect of TGF-beta1. Moreover, miRNA profiling demonstrated that MSCs differentiating into a certain lineage exhibit a specific miRNA expression profile. The complex regulatory network between miRNAs and transcription factors is suggested to play a crucial role in fine-tuning the differentiation of MSCs. These results demonstrate that commitment of mesenchymal stromal cells and further differentiation into specific lineages is regulated by interactions between MSCs, various growth and transcription factors, and miRNA-mediated translational repression of lineage-specific genes.

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TMPRSS2–ERG is the most frequent type of genomic rearrangement present in prostate tumors, in which the 5- prime region of the TMPRSS2 gene is fused to the ERG oncogene. TMPRSS2, containing androgen response elements (AREs), is regulated by androgens in the prostate. The truncated TMPRSS2-ERG fusion transcript is overexpressed in half of the prostate cancer patients. The formation of TMPRSS2-ERG transcript is an early event in prostate carcinogenesis and previous in vivo and in vitro studies have shown ectopic ERG expression to be associated with increased cell invasion. However, the molecular function of ERG and its role in cell signaling is poorly understood. In this study, genomic rearrangement of ERG with TMPRSS2 was studied by using comparative genomic hybridization (CGH) in prostate cancer samples. The biological processes associated with the ERG oncogene expression in prostate epithelial cells were studied, and the results were compared with findings observed in clinical prostate tumor samples. The gene expression data indicated that increased WNT signaling and loss of cell adhesion were a characteristic of TMPRSS2- ERG fusion positive prostate tumor samples. Up- regulation of WNT pathway genes were present in ERG positive prostate tumors, with frizzled receptor 4 (FZD4) presenting with the highest association with ERG overexpression, as verified by quantitative reverse transcription-PCR, immunostaining, and immunoblotting in TMPRSS2-ERG positive VCaP prostate cancer cells. Furthermore, ERG and FZD4 silencing increased cell adhesion by inducing active β1-integrin and E-cadherin expression in VCaP cells. Furthermore, we found a novel inhibitor, 4-(chloromethyl) benzoyl chloride which inhibited the WNT signaling and induced similar phenotypic effects as observed after ERG or FZD4 down regulation in VCaP cells. In conclusion, this work deepens our understanding on the complex oncogenic mechanisms of ERG in prostate cancer that may help in developing drugs against TMPRSS2-ERG positive tumors.

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The proportion of elderly people over 65 years of age in Finland is expected to grow to over 25% by the 2025. It has been estimated that elderly people today consume nearly 40% of all drugs. Age brings about number of physiological changes that may affect the disposition, metabolism and excretion of drugs. The function of heart, lungs, liver and kidneys decreases even in healthy people, as they get older. The proportion of total body water decreases and the relative fat percentage increases. Also several other factors such as concurrent diseases, concomitant medication and nutritional factors have an effect on drug therapy in elderly. Age increases the risk of adverse drug reactions, which most often are dose-dependent. Despite all this there are not enough studies involving the elderly people and the elderly are most often excluded from clinical trials. Oxycodone is a strong opioid analgesic, which is used to treat moderate or severe pain. Paracetamol is a widely used nonopioid analgesic, which has become popular in the treatment of pain in many patient groups. In this series of studies the pharmacokinetics of oral and intravenous oxicodone as well as intravenous paracetamol in the elderly and young adult patients were investigated. Also a study investigating the interaction of oral antibiotic clarityhromycin, a known cytochrome P450 (CYP) 3A4 inhibitor, with oxycodone pharmacokinetics and pharmacodynamics in elderly and young healthy volunteers was carried out. The pharmacokinetics of oxycodone showed a clear age depency. Patients over 70 years had 50-80% higher mean exposure to oral oxycodone and a twofold greater plasma concentration than young adults 12 h after ingestion of the drug. Elderly patients had 40-80% greater exposure to intravenous oxycodone and patients over 80 years had over twofold greater plasma concentrations 8 h post dose than the young adults. The elderly patients had also greater exposure to intra venous paracetamol compared to young adults. Clarithromycin increased the exposure to oral oxycodone in both young and elderly volunteers. The elderly had marked interindividual variation in the pharmacokinetics and pharmacodynamics when clarithromycin was given concomitantly with oxycodone. Because the pharmacokinetics of oxycodone and intravenous paracetamol depend on the age of the subject, it is important to titrate the analgesic dose individually in the elderly.

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To maintain a competitive development of the Brazilian aviculture, some measures must be taken to enable the identification and reduction of risks to the health of birds, as well as for the physical environment. Therefore, the aim of this study was to evaluate the effectiveness of three different systems of minimum ventilation (positive pressure - SVMP, negative pressure - SVMN and natural ventilation - SVMNat) in the air quality during the first 21 days of life of broiler chicks, during winter. Three points were selected along the length to verify ammonia, carbon monoxide and oxygen concentrations at 3a.m., 9a.m., 3p.m. and 9p.m., by the respiration level of birds and workers. The averages of pollutant gases did not exceed the tolerance levels for the three minimum ventilation systems evaluated, which is 20 and 10ppm for the birds level and 20 and 39ppm for the workers level, for ammonia and carbon monoxide, respectively. It was evident that the minimum ventilation systems were appropriately sized for the required minimum ambient air renovation, in respect to ventilation rates applied for the SVMN and SVMP systems, and with air velocity at levels that do not stress the chicks, including for the SVMNat. The three studied systems of minimum ventilation allowed the birds to externalize their productive performance, with values close to the ones considered satisfactory for all evaluated parameters, in accordance with the Brazilian aviculture standards.

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Kirjallisessa osassa tarkasteltiin pikornavirusten käyttöä geenivektoreina ja syöpäterapiassa. Pikornavirukset ovat positiivissäikeisiä RNA-viruksia, ja niiden genomi koostuu rakenteellisista kuoriproteiineista VP1-VP4 sekä ei-rakenteellisista proteiineista 2A-2C ja 3A-3D. Geenivektoritutkimukset ovat keskittyneet erilaisten inserttien kloonaamiseen virusten VP1-VP4-alueelle ja genomin 5'-päähän sekä näiden muutosten vaikutusten seuraamiseen virusten elinkierrossa solu- ja hiirimalleissa. Geenivektoreina on parhaiten toimineet coxsackievirukset B3, B4 ja A9 sekä mengo- ja poliovirus. Niitä on käytetty hiirissä mm. neuronien motorisen BDNF-reseptorin ilmentämiseen sekä hiiren interleukiini-10:n tuottamiseen selkäydinkanavan vaurioiden korjaamiseksi. Syöpäterapiatutkimuksissa on saatu lupaavia tuloksia coxsackieviruksilla A21, A13, A15 ja A18 sekä echo-, Seneca Valley 001- ja EMCV-viruksilla. Viruksilla on saatu mm. rintasyövän pääkasvain ja metastasoituneet etäpesäkkeet häviämään sekä eturauhassyövän kasvaimia pienenemään. Seneca Valley 001 -virus on osoittautunut tehokkaaksi syöpiä vastaan, joilla on neuroendokriinisiä ominaisuuksia. Viruksen käyttämistä faasi 2:n kliinisiin kokeisiin ollaan parhaillaan suunnittelemassa pienisoluisen keuhkosyövän ja lasten neuroendokriinisen syövän kohdalla. Kokeellisessa osassa optimoitiin RT-PCR-menetelmä coxsackievirus A7:n (CV-A7) genomin tuottamiseksi PCR-reaktiolla (FL-PCR). FL-PCR:n optimointi tehtiin vektoreilla, joihin oli kloonattu CV-A7-USSR- (USSR-pcDNA3) ja CV-A7-Parkerisolaattien (Parker-TA) genomit. Menetelmää käytettiin myöhemmin muiden CV-A7- virusisolaattien (275/58, ET1080 ja SVK) tutkimiseen. Näistä isolaateista eristettiin virus-RNA, joka käännettiin cDNA:ksi RT-entsyymillä. PCR:ssä käytetyt, CV-A7- spesifiset koettimet oli suunniteltu aiemmin sekvensoidun CV-A7-sekvenssin (GenBank AY421765) pohjalta. Infektiivisen kloonin tuottamiseksi USSR-pcDNA3- ja Parker-TA-vektoreista tuotettiin PCR:n avulla (T7-PCR) virusgenomin sisältävä DNAjakso, jonka 5'-päähän muodostui alukkeiden avulla T7RNA-polymeraasipromoottori ja 3'-päähän polyA-häntä. Työssä myös sekvensoitiin ja analysoitiin CV-A7-virusisolaatit Parker, USSR, 275/58, ET1080 ja SVK sekä kloonattiin täyspitkiä virusgenomeja cDNA-muodossa mutaatiokokeita varten. FL-PCR:n optimointi onnistui, ja neljä viidestä CV-A7-isolaatista sekvensoitiin. Virusgenomien pituus vaihteli 7403–7405 nt:n välillä. CV-A7-ET1080, -Parker ja - USSR osoittautuivat yli 99 % ja CV-A7-275/58 82,6 % nt samankaltaisiksi koko genomin pituudelta AY421765:en suhteen. Yksittäisten geenien ja proteiinien osalta CV-A7-275/58 oli 75,8–90,4 % nt ja 93,7–98,8 % aa samankaltainen muiden suhteen. Simplot-analyysissä 3B-geenialue oli heterogeenisin. CV-A7-SVK-isolaatti osoittautui echovirus kolmeksi. Infektiivistä kloonia ei saatu tuotettua T7-PCR-tuotteista.

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OBJETIVO: Avaliar o efeito da ventilação associada a frações inspiradas de oxigênio a 0,21 e 1,00 e do alopurinol (antioxidante) na isquemia-reperfusão pulmonar. MÉTODO: Foram utilizados 60 ratos Wistar, distribuídos aleatoriamente em seis grupos. O grupo 1 foi o controle; no grupo 2 os animais foram ventilados durante a isquemia-reperfusão pulmonar com FiO2 de 0,21; e no grupo 3, com FiO2 de 1,00. Os três grupos restantes 1A, 2A e 3A foram medicados com 100 mg/kg de alopurinol no pré-operatório e submetidos a procedimentos semelhantes aos grupos 1, 2 e 3, respectivamente. O modelo utilizado foi de isquemia-reperfusão normotérmica, in situ. O tempo de isquemia foi de 30 minutos, e o de reperfusão, de 10 minutos. Como parâmetros de avaliação foram utilizados a pressão arterial média sistêmica (PAM), a relação da pressão parcial de oxigênio/fração inspirada de oxigênio (PaO2/FiO2), a dosagem das substâncias reativas ao ácido tiobarbitúrico (TBARS) no tecido pulmonar e a relação entre peso pulmonar úmido e peso pulmonar seco. RESULTADOS: Em relação à PAM, ocorreu diminuição significante (p<0,05) entre os grupos 3 x 1, 2 x 2A e 3 x 3A. Na PaO2/FiO2 ocorreu diminuição significante (p<0,05) entre os grupos 3 x 2 e 3 x 3A. Nas TBARS ocorreu diminuição significante (p<0,05) entre os grupos 3 x 3A. Na relação peso pulmonar úmido/seco ocorreu aumento significante (p<0,05) entre os grupos 3 x 2, 2 x 2A e 3 x 3A. CONCLUSÕES: A ventilação com oxigênio a 21%, quando comparada à ventilação com oxigênio a 100%, apresentou diminuição menos acentuada da PAM, melhor relação entre PaO2/FiO2, e menor edema pulmonar. O uso de alopurinol no pré-operatório mostrou uma diminuição menos acentuada da PAM, melhor relação entre PaO2/FiO2, menor produção de TBARS e menor edema pulmonar, quando comparado aos resultados dos grupos que não o utilizaram.