Arachidonic acid metabolism by canine tracheal epithelial cells. Product formation and relationship to chloride secretion.

Les cellules épithéliales de trachée de chien, sous l'effet de l'ionophore calcique A23187 métabolisent l'acide arachidonique par la prostaglandine H synthase (prostaglandine D2) et des lipoxygénases (leukotriènes B4et C4). La prostaglandine D2stimule la sécrétion de Cl−(inhibition par l'indométhacine). Expériences de marquages, HPLC en phase inversée, spectrographie de masse, chromatographies en phase gazeuse et sur couche mince, essai radioimmunologique, mesures d'Isc

Tolfenamic Acid Induces Apoptosis and Growth Inhibition in Head and Neck Cancer: Involvement of NAG-1 Expression

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is induced by nonsteroidal anti-inflammatory drugs and possesses proapoptotic and antitumorigenic activities. Although tolfenamic acid (TA) induces apoptosis in head and neck cancer cells, the relationship between NAG-1 and TA has not been determined. This study investigated the induction of apoptosis in head and neck cancer cells treated by TA and the role of NAG-1 expression in this induction. TA reduced head and neck cancer cell viability in a dose-dependent manner and induced apoptosis. The induced apoptosis was coincident with the expression of NAG-1. Overexpression of NAG-1 enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. TA significantly inhibited tumor formation as assessed by xenograft models, and this result accompanied the induction of apoptotic cells and NAG-1 expression in tumor tissue samples. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression in head and neck squamous cell carcinoma, providing an additional mechanistic explanation for the apoptotic activity of TA

Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

<p>Abstract</p> <p>Background</p> <p>The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression.</p> <p>Methods</p> <p>First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays.</p> <p>Results</p> <p>NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group.</p> <p>Conclusion</p> <p>(1) A single dose of 25 mg/kg body weight NNK by intratracheal instillation is sufficient to induce preneoplastic lesions in Wistar rat lungs. (2) COX-2 takes part in NNK-induced tumorigenesis but is not involved in proliferation. (3) Aspirin and PEITC have protective effects in the early stages of tumor progression initiated by NNK.</p

Holographic Gravitational Anomaly and Chiral Vortical Effect

We analyze a holographic model with a pure gauge and a mixed gauge-gravitational Chern-Simons term in the action. These are the holographic implementations of the usual chiral and the mixed gauge-gravitational anomalies in four dimensional field theories with chiral fermions. We discuss the holographic renormalization and show that the gauge-gravitational Chern-Simons term does not induce new divergences. In order to cancel contributions from the extrinsic curvature at a boundary at finite distance a new type of counterterm has to be added however. This counterterm can also serve to make the Dirichlet problem well defined in case the gauge field strength vanishes on the boundary. A charged asymptotically AdS black hole is a solution to the theory and as an application we compute the chiral magnetic and chiral vortical conductivities via Kubo formulas. We find that the characteristic term proportional to T^2 is present also at strong coupling and that its numerical value is not renormalized compared to the weak coupling result.Comment: 27 pages, no figure

Modern tests of Lorentz invariance

Motivated by ideas about quantum gravity, a tremendous amount of effort over the past decade has gone into testing Lorentz invariance in various regimes. This review summarizes both the theoretical frameworks for tests of Lorentz invariance and experimental advances that have made new high precision tests possible. The current constraints on Lorentz violating effects from both terrestrial experiments and astrophysical observations are presented.Comment: Modified and expanded discussions of various points. Numerous references added. Version matches that accepted by Living Reviews in Relativit

The Confrontation between General Relativity and Experiment

The status of experimental tests of general relativity and of theoretical frameworks for analysing them is reviewed. Einstein's equivalence principle (EEP) is well supported by experiments such as the Eotvos experiment, tests of special relativity, and the gravitational redshift experiment. Future tests of EEP and of the inverse square law are searching for new interactions arising from unification or quantum gravity. Tests of general relativity at the post-Newtonian level have reached high precision, including the light deflection, the Shapiro time delay, the perihelion advance of Mercury, and the Nordtvedt effect in lunar motion. Gravitational-wave damping has been detected in an amount that agrees with general relativity to better than half a percent using the Hulse-Taylor binary pulsar, and other binary pulsar systems have yielded other tests, especially of strong-field effects. When direct observation of gravitational radiation from astrophysical sources begins, new tests of general relativity will be possible.Comment: 89 pages, 8 figures; an update of the Living Review article originally published in 2001; final published version incorporating referees' suggestion