Global characteristics of GRBs observed with INTEGRAL and the inferred large population of low-luminosity GRBs

INTEGRAL has two sensitive gamma-ray instruments that have detected 46 gamma-ray bursts (GRBs) up to July 2007. We present the spectral, spatial, and temporal properties of the bursts in the INTEGRAL GRB catalogue using data from the imager, IBIS, and spectrometer, SPI. Spectral properties of the GRBs are determined using power-law, Band model and quasithermal model fits to the prompt emission. Spectral lags, i.e. the time delay in the arrival of low-energy gamma-rays with respect to high-energy gamma-rays, are measured for 31 of the GRBs. The photon index distribution of power-law fits to the prompt emission spectra is consistent with that obtained by Swift. The peak flux distribution shows that INTEGRAL detects proportionally more weak GRBs than Swift because of its higher sensitivity in a smaller field of view. The all-sky rate of GRBs above ~0.15 ph cm^-2 s^-1 is ~1400 yr^-1 in the fully coded field of view of IBIS. Two groups are identified in the spectral lag distribution, one with short lags <0.75 s (between 25-50 keV and 50-300 keV) and one with long lags >0.75 s. Most of the long-lag GRBs are inferred to have low redshifts because of their long spectral lags, their tendency to have low peak energies and their faint optical and X-ray afterglows. They are mainly observed in the direction of the supergalactic plane with a quadrupole moment of Q=-0.225+/-0.090 and hence reflect the local large-scale structure of the Universe. The rate of long-lag GRBs with inferred low luminosity is ~25% of Type Ib/c supernovae. Some of these bursts could be produced by the collapse of a massive star without a supernova or by a different progenitor, such as the merger of two white dwarfs or a white dwarf with a neutron star or black hole, possibly in the cluster environment without a host galaxy.Comment: 22 pages, 13 figures and appendix, accepted for publication in A&A, added and updated reference

GRB 050904 at redshift 6.3: observations of the oldest cosmic explosion after the Big Bang

We present optical and near-infrared observations of the afterglow of the gamma-ray burst GRB 050904. We derive a photometric redshift z = 6.3, estimated from the presence of the Lyman break falling between the I and J filters. This is by far the most distant GRB known to date. Its isotropic-equivalent energy is 3.4x10^53 erg in the rest-frame 110-1100 keV energy band. Despite the high redshift, both the prompt and the afterglow emission are not peculiar with respect to other GRBs. We find a break in the J-band light curve at t_b = 2.6 +- 1.0 d (observer frame). If we assume this is the jet break, we derive a beaming-corrected energy E_gamma = (4-12)x10^51 erg. This limit shows that GRB 050904 is consistent with the Amati and Ghirlanda relations. This detection is consistent with the expected number of GRBs at z > 6 and shows that GRBs are a powerful tool to study the star formation history up to very high redshift.Comment: 3 figures, 5 pages, accepted for publication in A&A Letters. One figure added, minor modifications. Full author list in the pape

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

Arachidonic acid (AA) and its metabolites have recently generated a heightened interest due to growing evidence of their significant role in cancer biology. Thus, inhibitors of the AA cascade, first and foremost COX inhibitors, which have originally been of interest in the treatment of inflammatory conditions and certain types of cardiovascular disease, are now attracting attention as an arsenal against cancer. An increasing number of investigations support their role in cancer chemoprevention, although the precise molecular mechanisms that link levels of AA, and its metabolites, with cancer progression have still to be elucidated. This article provides an overview of the AA cascade and focuses on the roles of its inhibitors and their implication in cancer treatment. In particular, emphasis is placed on the inhibition of cell proliferation and neo-angiogenesis through inhibition of the enzymes COX-2, 5-LOX and CYP450. Downstream effects of inhibition of AA metabolites are analysed and the molecular mechanisms of action of a selected number of inhibitors of catalytic pathways reviewed. Lastly, the benefits of dietary omega-3 fatty acids and their mechanisms of action leading to reduced cancer risk and impeded cancer cell growth are mentioned. Finally, a proposal is put forward, suggesting a novel and integrated approach in viewing the molecular mechanisms and complex interactions responsible for the involvement of AA metabolites in carcinogenesis and the protective effects of omega-3 fatty acids in inflammation and tumour prevention

Anesthésie générale par rachi-cocaïnisation lombo-sacrée suivant notre technique, par le Dr G. Le Filliatre,...

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Mécanismes inflammatoires liés à l'activation des fibres sensitives de la patte postérieure de rat (implication dans l'oedème provoqué par une hypertension veineuse aiguë. Effets des composés INO 5042 et INO 5207)

Nous nous sommes intéressés aux mécanismes inflammatoires liés à l'activation des fibres sensitives du nerf , saphène, plus particulièrement aux effets de la substance P. Dans cette optique, eux modèles expérimentaux ont été mis en place, permettant de mesurer indépendamment, au niveau de la patte postérieure de rat, la vasodilatation périphérique et le volume d'oedème consécutifs à une courte stimulation du nerf saphène. Conjointement à l'activation directe des cellules endothéliales, phénomène classiquement décrit dans la littérature, l'œdème provoqué par la substance P est fortement dépendant de l'histamine libérée par les mastocytes. Les cystéinyl-leucotriènes, d'origine leucocytaire, jouent également un rôle prépondérant dans le développement de l'œdème neurogène. La dégranulation leucocytaire serait sous la dépendance du PAF. L'absence d'effet des inhibiteurs deCOX sur l'œdème neurogène exclut une participation des prostaglandines au phénomène inflammatoire observé. Cette étude souligne également l'importance du NO dans la mise en place de l'œdème. La NOS endothéliale joue un rôle protecteur. Le NO d'origine endothéliale piègerait les dérivés de l'oxygène, agents pro- inflammatoires libérés par les mastocytes. A l'inverse, la NOS neuronale favoriserait le développement de l'œdème et de la vasodilatation provoqués par la stimulation du nerf saphène, en activant la libération des neuropeptides. Cette étude s'est également intéressée à l'implication possible de l'inflammation neurogène dans l'initiation de l'insuffisance veineuse chronique. Ainsi, le CGRP et la substance P participent au développement de l'œdème provoqué par une hyperpression veineuse aiguë, et ceci dès les premières minutes. De plus, ce phénomène inflammatoire est réduit par le INa 5207, composé inhibant également l'œdème neurogène. Le INa 5207 est toutefois moins efficace sur la vasodilatation neurogène, laissant supposer la présence de deux sites distincts et/ou l'expression du récepteur limitée à certaines fibres sensitives du nerf saphène.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Cyclo-oxygenase and lipoxygenase pathways in mast cell dependent-neurogenic inflammation induced by electrical stimulation of the rat saphenous nerve

1. We investigated the role of arachidonic acid metabolism and assessed the participation of mast cells and leukocytes in neurogenic inflammation in rat paw skin. We compared the effect of lipoxygenase (LOX) and cyclo-oxygenase (COX) inhibitors on oedema induced by saphenous nerve stimulation, substance P (SP), and compound 48/80. 2. Intravenous (i.v.) pre-treatment with a dual COX/LOX inhibitor (RWJ 63556), a dual LOX inhibitor/cysteinyl-leukotriene (CysLt) receptor antagonist (Rev 5901), a LOX inhibitor (AA 861), a five-lipoxygenase activating factor (FLAP) inhibitor (MK 886), or a glutathione S-transferase inhibitor (ethacrynic acid) significantly inhibited (40 to 60%) the development of neurogenic oedema, but did not affect cutaneous blood flow. Intradermal (i.d.) injection of LOX inhibitors reduced SP-induced oedema (up to 50% for RWJ 63556 and MK 886), whereas ethacrynic acid had a potentiating effect. 3. Indomethacin and rofecoxib, a highly selective COX-2 inhibitor, did not affect neurogenic and SP-induced oedema. Surprisingly, the structurally related COX-2 inhibitors, NS 398 and nimesulide, significantly reduced both neurogenic and SP-induced oedema (70% and 42% for neurogenic oedema, respectively; 49% and 46% for SP-induced oedema, respectively). 4. COX-2 mRNA was undetectable in saphenous nerves and paw skin biopsy samples, before and after saphenous nerve stimulation. 5. A mast cell stabilizer, cromolyn, and a H(1) receptor antagonist, mepyramine, significantly inhibited neurogenic (51% and 43%, respectively) and SP-induced oedema (67% and 63%, respectively). 6. The co-injection of LOX inhibitors and compound 48/80 did not alter the effects of compound 48/80. Conversely, ethacrynic acid had a significant potentiating effect. The pharmacological profile of the effect of COX inhibitors on compound 48/80-induced oedema was similar to that of neurogenic and SP-induced oedema. 7. The polysaccharide, fucoidan (an inhibitor of leukocyte rolling) did not affect neurogenic or SP-induced oedema. 8. Thus, (i) SP-induced leukotriene synthesis is involved in the development of neurogenic oedema in rat paw skin; (ii) this leukotriene-mediated plasma extravasation might be independent of mast cell activation and/or of the adhesion of leukocytes to the endothelium; (iii) COX did not appear to play a significant role in this process