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1.
Phys Rev Lett ; 126(7): 072501, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33666458

RESUMO

We studied the proton-rich T_{z}=-1 nucleus ^{70}Kr through inelastic scattering at intermediate energies in order to extract the reduced transition probability, B(E2;0^{+}→2^{+}). Comparison with the other members of the A=70 isospin triplet, ^{70}Br and ^{70}Se, studied in the same experiment, shows a 3σ deviation from the expected linearity of the electromagnetic matrix elements as a function of T_{z}. At present, no established nuclear structure theory can describe this observed deviation quantitatively. This is the first violation of isospin symmetry at this level observed in the transition matrix elements. A heuristic approach may explain the anomaly by a shape change between the mirror nuclei ^{70}Kr and ^{70}Se contrary to the model predictions.

2.
Phys Rev Lett ; 124(15): 152501, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32357059

RESUMO

The lifetimes of the first excited 2^{+} states in the N=Z nuclei ^{80}Zr, ^{78}Y, and ^{76}Sr have been measured using the γ-ray line shape method following population via nucleon-knockout reactions from intermediate-energy rare-isotope beams. The extracted reduced electromagnetic transition strengths yield new information on where the collectivity is maximized and provide evidence for a significant, and as yet unexplained, odd-odd vs even-even staggering in the observed values. The experimental results are analyzed in the context of state-of-the-art nuclear density-functional model calculations.

3.
Phys Rev Lett ; 124(6): 062501, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32109090

RESUMO

The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N=Z) nuclide _{44}^{88}Ru_{44} has been measured using the combination of the Advanced Gamma Tracking Array (AGATA) spectrometer, the NEDA and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in ^{88}Ru were populated via the ^{54}Fe(^{36}Ar,2nγ)^{88}Ru^{*} fusion-evaporation reaction at the Grand Accélérateur National d'Ions Lourds (GANIL) accelerator complex. The observed γ-ray cascade is assigned to ^{88}Ru using clean prompt γ-γ-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N>Z nuclides. The direct observation of such a "delayed" rotational alignment in a deformed N=Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.

4.
Phys Rev Lett ; 122(6): 062501, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30822069

RESUMO

New rotational bands built on the ν(h_{11/2}) configuration have been identified in ^{105}Pd. Two bands built on this configuration show the characteristics of transverse wobbling: the ΔI=1 transitions between them have a predominant E2 component and the wobbling energy decreases with increasing spin. The properties of the observed wobbling bands are in good agreement with theoretical results obtained using constrained triaxial covariant density functional theory and quantum particle rotor model calculations. This provides the first experimental evidence for transverse wobbling bands based on a one-neutron configuration, and also represents the first observation of wobbling motion in the A∼100 mass region.

5.
Phys Rev Lett ; 119(19): 192503, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29219499

RESUMO

In this Letter, the observation of two previously unknown isotopes is presented for the first time: ^{72}Rb with 14 observed events and ^{77}Zr with one observed event. From the nonobservation of the less proton-rich nucleus ^{73}Rb, we derive an upper limit for the ground-state half-life of 81 ns, consistent with the previous upper limit of 30 ns. For ^{72}Rb, we have measured a half-life of 103(22) ns. This observation of a relatively long-lived odd-odd nucleus, ^{72}Rb, with a less exotic odd-even neighbor, ^{73}Rb, being unbound shows the diffuseness of the proton drip line and the possibility of sandbanks to exist beyond it. The ^{72}Rb half-life is consistent with a 5^{+}→5/2^{-} proton decay with an energy of 800-900 keV, in agreement with the atomic mass evaluation proton-separation energy as well as results from the finite-range droplet model and shell model calculations using the GXPF1A interaction. However, we cannot explicitly exclude the possibility of a proton transition between 9^{+}(^{72}Rb)→9/2^{+}(^{71}Kr) isomeric states with a broken mirror symmetry. These results imply that ^{72}Kr is a strong waiting point in x-ray burst rp-process scenarios.

6.
Nature ; 469(7328): 68-71, 2011 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-21179086

RESUMO

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.

7.
Phys Rev Lett ; 112(14): 142502, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24765947

RESUMO

The transition rates from the yrast 2+ and 4+ states in the self-conjugate 72Kr nucleus were studied via lifetime measurements employing the GRETINA array with a novel application of the recoil-distance method. The large collectivity observed for the 4+→2+ transition suggests a prolate character of the excited states. The reduced collectivity previously reported for the 2+→0+ transition was confirmed. The irregular behavior of collectivity points to the occurrence of a rapid oblate-prolate shape transition in 72Kr, providing stringent tests for advanced theories to describe the shape coexistence and its evolution.

8.
Phys Rev Lett ; 107(17): 172502, 2011 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-22107511

RESUMO

A ß-decaying high-spin isomer in (96)Cd, with a half-life T(1/2)=0.29(-0.10)(+0.11) s, has been established in a stopped beam rare isotope spectroscopic investigations at GSI (RISING) experiment. The nuclei were produced using the fragmentation of a primary beam of (124)Xe on a (9)Be target. From the half-life and the observed γ decays in the daughter nucleus, (96)Ag, we conclude that the ß-decaying state is the long predicted 16(+) "spin-gap" isomer. Shell-model calculations, using the Gross-Frenkel interaction and the πν(p(1/2),g(9/2)) model space, show that the isoscalar component of the neutron-proton interaction is essential to explain the origin of the isomer. Core excitations across the N=Z=50 gaps and the Gamow-Teller strength, B(GT) distributions have been studied via large-scale shell-model calculations using the πν(g,d,s) model space to compare with the experimental B(GT) value obtained from the half-life of the isomer.

9.
Pulm Pharmacol Ther ; 24(1): 100-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20851205

RESUMO

BACKGROUND: There is evidence that peroxynitrite is generated in pulmonary hypertension and we have therefore investigated whether peroxynitrite can cause proliferation of pulmonary artery cells. METHODS: Bovine pulmonary artery endothelial (PAEC) and smooth muscle cells (PASMC) were exposed to peroxynitrite solution or to the peroxynitrite generating compound, 3-morpholinosydnonimine (SIN-1). Vascular cell proliferation was determined by cell count and (3)H-thymidine incorporation. Protein biochemistry was by western blot analysis. RESULTS: Transient exposure to peroxynitrite stimulated the proliferation of PASMC (peroxynitrite 0.2 nM-2 µM) and PAEC (peroxynitrite 0.2 µM). Peroxynitrite 0.2 µM stimulated DNA synthesis in PASMC cell by 200 ± 22% and in PAEC by 137 ± 4%. DNA synthesis in PAEC and PASMC was also stimulated by the peroxynitrite generator SIN-1 2 µM. Cell proliferation was accompanied by activation of ERK, which peaked at 15 min and remained elevated for 12 h in PASMC. However peroxynitrite at the concentrations used in this study did not activate the stress pathways p38 mitogen activated protein kinase (MAPK) or Jun N-terminal kinase (JNK). Peroxynitrite-induced proliferation and ERK phosphorylation in PASMC were abolished by the peroxynitrite scavenger ebselen 5 µM. Peroxynitrite-induced proliferation and extracellular signal-regulated kinase (ERK) phosphorylation in PASMC was prevented by selective inhibitors of MAP kinase kinase (MEK) (U0126 5 µM, PD98059 50 µM), Raf-1 (Raf-1 kinase inhibitor 10 µM), Ras (FPT II and FPT III 10 µM) and protein kinase C (PKC) (GF109203X 10 µM). Inhibition of EGF or PDGF receptor signaling using AG-1296, AG-1478 or imatinib prevented peroxynitrite-induced cell proliferation and ERK phosphorylation in PASMC. CONCLUSION: Peroxynitrite can stimulate proliferation of pulmonary artery cells, involving ERK, PKC and EGF or PDGF receptors.


Assuntos
Células Endoteliais/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Ácido Peroxinitroso/farmacologia , Proteína Quinase C/fisiologia , Artéria Pulmonar/efeitos dos fármacos , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais/fisiologia , Receptores ErbB/fisiologia , Feminino , Quinases de Proteína Quinase Ativadas por Mitógeno/fisiologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/fisiologia , Proteínas Proto-Oncogênicas c-raf/fisiologia , Artéria Pulmonar/citologia , Receptores do Fator de Crescimento Derivado de Plaquetas/fisiologia , Proteínas ras/fisiologia
10.
Phys Rev Lett ; 104(16): 162501, 2010 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-20482043

RESUMO

A measurement of the energy and spin of superdeformed states in 190Hg, obtained through the observation of transitions directly linking superdeformed and normal states, expands the number of isotopes in which binding energies at superdeformation are known. Comparison with neighboring nuclei shows that two-proton separation energies are higher in the superdeformed state than in the normal state, despite the lower Coulomb barrier and lower total binding energy. This unexpected result provides a critical test for nuclear models.

11.
J Environ Monit ; 12(9): 1747-55, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20697627

RESUMO

Precipitation samples have been collected on a monthly basis from a network of 10 sites in Great Britain (GB) in order to estimate background mercury (Hg) deposition in the rural environment. Collection started in February 2005 and results presented here cover the period up to June 2009. The annual volume-weighted mean (AVWM) Hg concentrations range from 1.0 ng L(-1) at Cockley Beck in the Lake District in 2006 to 8.8 ng L(-1) at Heigham Holmes on the Norfolk Coast England in 2008. The largest validated solution concentrations were 33.7 ng L(-1) Hg measured at Cockley Beck in May 2008. The large difference in rainfall amount between sites means that the remote site at Cockley Beck has both the lowest long-term AVWM concentration (1.6 ng L(-1)) and the greatest annual flux is greatest at 43 mg ha(-1) yr(-1). Predicted deposition tends to be much greater in western Britain where the greater rainfall occurs. Because some observations are very close to the analytical detection limit (1.0 ng L(-1)), rigorous cleaning procedures, the use of replicate samplers to monitor contamination, and the inclusion of 'bottle blanks' are required to obtain valid measurements of Hg in the bulk deposition. Deposition in rural sites is equivalent to about 10% of the estimated magnitude of known emissions in GB.


Assuntos
Monitoramento Ambiental , Mercúrio/análise , Chuva/química , Poluentes Químicos da Água/análise , Atmosfera/química , Mercúrio/normas , Reino Unido , Poluentes Químicos da Água/química , Poluição Química da Água/estatística & dados numéricos
12.
Sci Total Environ ; 382(2-3): 199-213, 2007 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-17555799

RESUMO

Critical loads are the basis for policies controlling emissions of acidic substances in Europe and elsewhere. They are assessed by several elaborate and ingenious models, each of which requires many parameters, and have to be applied on a spatially-distributed basis. Often the values of the input parameters are poorly known, calling into question the validity of the calculated critical loads. This paper attempts to quantify the uncertainty in the critical loads due to this "parameter uncertainty", using examples from the UK. Models used for calculating critical loads for deposition of acidity and nitrogen in forest and heathland ecosystems were tested at four contrasting sites. Uncertainty was assessed by Monte Carlo methods. Each input parameter or variable was assigned a value, range and distribution in an objective a fashion as possible. Each model was run 5000 times at each site using parameters sampled from these input distributions. Output distributions of various critical load parameters were calculated. The results were surprising. Confidence limits of the calculated critical loads were typically considerably narrower than those of most of the input parameters. This may be due to a "compensation of errors" mechanism. The range of possible critical load values at a given site is however rather wide, and the tails of the distributions are typically long. The deposition reductions required for a high level of confidence that the critical load is not exceeded are thus likely to be large. The implication for pollutant regulation is that requiring a high probability of non-exceedance is likely to carry high costs. The relative contribution of the input variables to critical load uncertainty varied from site to site: any input variable could be important, and thus it was not possible to identify variables as likely targets for research into narrowing uncertainties. Sites where a number of good measurements of input parameters were available had lower uncertainties, so use of in situ measurement could be a valuable way of reducing critical load uncertainty at particularly valuable or disputed sites. From a restricted number of samples, uncertainties in heathland critical loads appear comparable to those of coniferous forest, and nutrient nitrogen critical loads to those of acidity. It was important to include correlations between input variables in the Monte Carlo analysis, but choice of statistical distribution type was of lesser importance. Overall, the analysis provided objective support for the continued use of critical loads in policy development.


Assuntos
Ecossistema , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Incerteza , Chuva Ácida/análise , Modelos Teóricos , Método de Monte Carlo , Nitrogênio/análise , Poluentes do Solo/normas , Árvores , Reino Unido , Gerenciamento de Resíduos/estatística & dados numéricos
13.
Nucleic Acids Res ; 29(4): 914-20, 2001 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11160923

RESUMO

Single-stranded DNA binding proteins (SSBs) play central roles in cellular and viral processes involving the generation of single-stranded DNA. These include DNA replication, homologous recombination and DNA repair pathways. SSBs bind DNA using four 'OB-fold' (oligonucleotide/oligosaccharide binding fold) domains that can be organised in a variety of overall quaternary structures. Thus eubacterial SSBs are homotetrameric whilst the eucaryal RPA protein is a heterotrimer and euryarchaeal proteins vary significantly in their subunit compositions. We demonstrate that the crenarchaeal SSB protein is an abundant protein with a unique structural organisation, existing as a monomer in solution and multimerising on DNA binding. The protein binds single-stranded DNA distributively with a binding site size of approximately 5 nt per monomer. Sulfolobus SSB lacks the zinc finger motif found in the eucaryal and euryarchaeal proteins, possessing instead a flexible C-terminal tail, sensitive to trypsin digestion, that is not required for DNA binding. In comparison with Escherichia coli SSB, the tail may play a role in protein-protein interactions during DNA replication and repair.


Assuntos
Proteínas Arqueais/metabolismo , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/metabolismo , Sulfolobus/genética , Sequência de Aminoácidos , Proteínas Arqueais/química , Proteínas Arqueais/genética , Proteínas Arqueais/isolamento & purificação , Clonagem Molecular , Reagentes de Ligações Cruzadas/metabolismo , DNA de Cadeia Simples/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/isolamento & purificação , Escherichia coli/química , Escherichia coli/genética , Fluorescência , Glutaral/metabolismo , Dados de Sequência Molecular , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Sulfolobus/química , Tripsina/metabolismo , Triptofano/metabolismo
14.
Sci Total Environ ; 360(1-3): 233-45, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16242758

RESUMO

The Environmental Information System for Planners (EISP) is a proof of concept web-based system designed to support decision making within the UK planning framework by making information on environmental issues more widely accessible. It incorporates relevant outputs from the Natural Environment Research Council (NERC) Urban Regeneration and the Environment (URGENT) research programme and from research directly commissioned by the Office of the Deputy Prime Minister (ODPM). It supports three principal planning functions carried out by local authorities: pre-planning enquiries, development control decisions and strategic planning. Eleven environmental science themes are incorporated: Air quality, Shallow undermining, Landslide susceptibility, Groundwater protection, Flood risk, Drainage, Land contamination, Proximity to landfill, Biodiversity, Natural and Man-made heritage. Decision flow diagrams represent detailed analysis of workflow in each theme, taking account of best practice, regulatory responsibilities and planning guidance. Industry-standard web technologies integrate the flows and provide access to the system via secure web pages. Underpinning the system is an environmental geographical information system (GIS) containing up-to-date data, information and models relevant to each theme. The modular system design allows new legislation and local priorities and datasets to be easily incorporated. Web technology delivers information and research data that have hitherto been difficult for the non-specialist to access and have therefore been under-exploited. The study has demonstrated a successful application of the principles of e-Governance in an area where informed decisions commonly require specialist information. The system, if rolled out nationally, offers potential economic benefits and efficiency savings for both planners and developers.


Assuntos
Planejamento de Cidades , Técnicas de Apoio para a Decisão , Meio Ambiente , Sistemas de Informação , Tomada de Decisões , Internet , Reino Unido
15.
Sci Total Environ ; 360(1-3): 196-204, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16297440

RESUMO

We examined the biodiversity of urban habitats in Birmingham (England) using a combination of field surveys of plants and carabid beetles, genetic studies of four species of butterflies, modelling the anthropochorous nature of the floral communities and spatially explicit modelling of selected mammal species. The aim of the project was to: (i) understand the ecological characteristics of the biota of cities model, (ii) examine the effects of habitat fragment size and connectivity upon the ecological diversity and individual species distributions, (iii) predict biodiversity in cities, and (iv) analyse the extent to which the flora and fauna utilise the 'urban greenways' both as wildlife corridors and as habitats in their own right. The results suggest that cities provide habitats for rich and diverse range of plants and animals, which occur sometimes in unlikely recombinant communities. The studies on carabids and butterflies illustrated the relative importance of habitat quality on individual sites as opposed to site location within the conurbation. This suggests that dispersal for most of our urban species is not a limiting factor in population persistence, although elements of the woodland carabid fauna did appear to have some geographical structuring. Theoretical models suggested that dormice and water voles may depend on linear habitats for dispersal. The models also indicated that other groups, such as small and medium sized mammals, may use corridors, although field-based research did not provide any evidence to suggest that plants or invertebrates use urban greenways for dispersal. This finding indicates the importance of identifying a target species or group of species for urban greenways intended as dispersal routeways rather than as habitat in their own right. Their importance for most groups is rather that greenways provide a chain of different habitats permeating the urban environment. We suggest that planners can have a positive impact on urban biodiversity by slowing the pace of redevelopment and by not hurrying to tidy up and redevelop brownfield sites.


Assuntos
Biodiversidade , Cidades , Meio Ambiente , Animais , Borboletas/classificação , Borboletas/genética , Besouros , Variação Genética , Sistemas de Informação Geográfica , Mamíferos , Modelos Teóricos , Plantas , Dinâmica Populacional , Reino Unido , Urbanização
16.
Circulation ; 104(13): 1538-43, 2001 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-11571249

RESUMO

BACKGROUND: Mitogenic stimuli present at the site of coronary arterial balloon injury contribute to the progression and development of a restenotic lesion, many signaling through a common pathway involving the small G protein p21(ras). Our aim was to demonstrate in biochemical studies that farnesyl protein transferase inhibitor III (FPTIII) is an inhibitor of p21(ras) processing and that when it is given locally in vivo at the site of coronary balloon injury in a porcine model, it can inhibit neointima formation. METHODS AND RESULTS: FPTIII (1 to 25 micromol/L) concentration-dependently reduced p21(ras) levels in porcine coronary artery smooth muscle cell membranes. FPTIII also prevented p42/p44 MAPK activation and DNA synthesis in response to platelet-derived growth factor in these cells at a concentration of 25 micromol/L. Application of 25 micromol/L FPTIII locally for 15 minutes to balloon-injured porcine coronary arteries in vivo prevented neointima formation assessed at 4 weeks, reduced proteoglycan deposition, and inhibited adventitial hypertrophy. Coronary arteries from FPTIII-treated pigs had no deterioration in contraction or in endothelium-dependent relaxation. CONCLUSIONS: The study demonstrates in the pig that short-term local delivery of inhibitors of p21(ras)-dependent mitogenic signal transduction prevents restenosis after balloon angioplasty.


Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Angioplastia Coronária com Balão/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Organofosfonatos/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Organofosfonatos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Suínos , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologia , Doenças Vasculares/etiologia , Doenças Vasculares/prevenção & controle
17.
Trends Pharmacol Sci ; 15(2): 47-53, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8165724

RESUMO

Hypoxia has marked effects on artery calibre, which reflects important physiological control mechanisms that are altered in disease states. Hypoxia modifies the release of mediators, especially from the endothelium, and influences smooth muscle membrane potential and Ca2+ regulation. In this review, Roger Wadsworth evaluates the vasoconstrictor and vasodilator effects of hypoxia studied in vitro. In the future, drugs developed to act on the mediators or smooth muscle may be beneficial in the therapy of, for example, pulmonary hypertension or coronary vasospasm.


Assuntos
Hipóxia/fisiopatologia , Músculo Liso Vascular/metabolismo , Vasoconstrição , Vasodilatação , Animais , Humanos , Hipóxia/metabolismo , Potenciais da Membrana , Prostaglandinas/metabolismo
18.
Pharmacol Ther ; 84(3): 355-65, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10665834

RESUMO

Superoxide formation in pulmonary tissue is modulated by cytokines, PO2, shear force, and disease states, and can be stimulated by drugs. Superoxide has diverse actions on pulmonary cells, including smooth muscle contraction, interaction with redox enzymes, cell proliferation, and gene transcription. In the lungs, there is an impressive array of specific defence mechanisms that destroy superoxide, especially superoxide dismutase (SOD) and metallothionein. Superoxide formation is increased in hyperoxia (e.g., oxygen therapy); however, superoxide-forming enzymes also can be up-regulated in hypoxia. Superoxide has been implicated in acute respiratory distress syndrome, lung ischaemia-reperfusion injury, and lung transplantation. Novel approaches to therapy have been explored, including SOD gene therapy and SOD targeting to the lung. In the future, new drugs interacting with superoxide may provide significant advances in the treatment of lung diseases.


Assuntos
Artéria Pulmonar/metabolismo , Superóxidos/metabolismo , Animais , Divisão Celular , Permeabilidade da Membrana Celular , Terapia Genética , Humanos , Hiperóxia/metabolismo , Hipóxia/metabolismo , Pneumopatias/metabolismo , Pneumopatias/terapia , Metalotioneína/metabolismo , Artéria Pulmonar/citologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo , Transcrição Gênica
19.
Pharmacol Ther ; 68(2): 233-46, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8719969

RESUMO

Chronic hypoxia (CH) is associated with several cardiopulmonary disorders. In vitro and in vivo studies have established the morphological changes, but yielded conflicting results about the functional changes induced by CH in the pulmonary vascular bed. CH increases the responsiveness to endothelium-dependent vasodilators in perfused lungs; however, in artery rings, a reduction is found in endothelium-dependent vasodilation. In CH, vasoconstriction induced by endothelin-1 is enhanced and vasodilation produced by atrial natriuretic peptide and K+ channel openers is increased. Vasoconstriction produced by acute hypoxia can be either enhanced or reduced by CH, depending on the experimental protocol. An understanding of the functional changes associated with CH is particularly important for a rational approach to the treatment of disorders associated with CH.


Assuntos
Hipóxia/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Doença Crônica , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Hipóxia/tratamento farmacológico , Técnicas In Vitro , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/fisiologia , Artéria Pulmonar/fisiopatologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia
20.
Cell Signal ; 9(1): 109-16, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9067639

RESUMO

We have examined the regulation of the 70 kDa ribosomal S6 kinase (p70s6k) by the G-protein-coupled receptor agonist alpha-thrombin and the role of this signalling molecule in the mitogenic effect of thrombin in cultured bovine pulmonary arterial (PA) fibroblasts. Thrombin stimulated p70s6k activity in a time and concentration-dependent manner which was abolished by the macrolide rapamycin. The phosphatidylinositol (PI) 3-kinase inhibitor wortmannin also completely blocked p70s6k activity in response to thrombin but did not affect p70s6k activity evoked by platelet-derived growth factor (PDGF) at a concentration that abrogated PDGF-stimulated PI 3-kinase activity. Activation of p70s6k by thrombin, but not PDGF, was also inhibited (by 48.3 +/- 5.4%) by pre-incubation of cells with pertussis toxin (PTX). Downregulation of protein kinase C (PKC) alpha and epsilon isoforms by pretreatment of fibroblasts for 48 h with phorbol 12-myristate 13-acetate (PMA), markedly attenuated both thrombin and PDGF-stimulated p70s6k activation (by 74.8 +/- 4.4% and 82.3 +/- 7.9% respectively). Thrombin also strongly stimulated (over 100 fold) the incorporation of [3H]thymidine into growth arrested PA fibroblasts which was inhibited by rapamycin (by 33.6 +/- 2.0%). From these results we propose that in PA fibroblasts: 1) thrombin stimulates the activation of p70s6k in a manner consistent with an involvement of a heterotrimeric G protein of the G(i) family, a PI 3-kinase other than the PI 3-kinase involved in signalling by PDGF, and PKC. 2) a p70s6k-dependent pathway plays a role in mitogenic signalling by thrombin.


Assuntos
DNA/biossíntese , Mitógenos/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Trombina/farmacologia , Androstadienos/farmacologia , Animais , Bovinos , Ativação Enzimática , Feminino , Fibroblastos , Toxina Pertussis , Fosfatidilinositol 3-Quinases , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteína Quinase C/metabolismo , Artéria Pulmonar , Proteínas Quinases S6 Ribossômicas , Fatores de Virulência de Bordetella/farmacologia , Wortmanina
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