Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance.

Effective treatment of chronic pain with morphine is limited by decreases in the drug’s analgesic action with chronic administration (antinociceptive tolerance). Because opioids are mainstays of pain management, restoring their efficacy has great clinical importance. We have recently reported that formation of peroxynitrite (ONOO(−), PN) in the dorsal horn of the spinal cord plays a critical role in the development of morphine antinociceptive tolerance and have further documented that nitration and enzymatic inactivation of mitochondrial superoxide dismutase (MnSOD) at that site provides a source for this nitroxidative species. We now report for the first time that antinociceptive tolerance is also associated with the inactivation of MnSOD at supraspinal sites. Inactivation of MnSOD led to nitroxidative stress as evidenced by increased levels of products of oxidative DNA damage and activation of the nuclear factor poly (ADP-ribose) polymerase in whole brain homogenates. Co-administration of morphine with potent Mn porphyrin-based peroxynitrite scavengers, (MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+)) (1) restored the enzymatic activity of MnSOD, (2) attenuated PN derived nitroxidative stress, and (3) blocked the development of morphine induced antinociceptive tolerance. The more lipophilic analogue, MnTnHex-2-PyP(5+) was able to cross the blood brain barrier at higher levels than its lipophylic counterpart MnTE-2-PyP(5+) and was about 30 fold more efficacious. Collectively, these data suggest that peroxynitrite mediated enzymatic inactivation of supraspinal MnSOD provides a source of nitroxidative stress, which in turn contributes to central sensitization associated with the development of morphine antinociceptive tolerance. These results support our general contention that PN-targeted therapeutics may have potential as adjuncts to opiates in pain management

Near threshold eta production in proton-proton collisions

The total cross section for the near threshold eta production in proton-proton collisions has been investigated with the assumption that the production mechanism is due to the emission of a meson x (pi, eta, sigma) from one of the nucleons followed by a x N --> eta N transition on the second one. The x N --> eta N amplitudes are generated from the unitary multi-channel multi-resonance model which has recently been constructed in analyzing the pi N scattering and pi N --> eta N reaction. The initial and final pp distortions are calculated from a coupled-channel pi-NN model which describes the NN scattering data up to about 2 GeV. With the x-NN vertex functions taken from the Bonn potential, the predicted total cross sections of threshold pp --> eta pp reaction are in good agreement with the data. In contrast to previous works, we find that the eta-exchange plays an important role. The effect of the two-pion exchange, simulated by sigma- exchange, is found to be significant but not as dominant as the vector meson-exchange introduced in previous works.Comment: 9 pages (latex: elsart.sty) + 3 figures (PostScript gzip+uuencode) Submitted to Phys.Lett.

When linearity prevails over hierarchy in syntax

Hierarchical structure has been cherished as a grammatical universal. We use experimental methods to show where linear order is also a relevant syntactic relation. An identical methodology and design were used across six research sites on South Slavic languages. Experimental results show that in certain configurations, grammatical production can in fact favor linear order over hierarchical structure. However, these findings are limited to coordinate structures and distinct from the kind of production errors found with comparable configurations such as “attraction” errors. The results demonstrate that agreement morphology may be computed in a series of steps, one of which is partly independent from syntactic hierarchy

The η\eta-3N problem with separable interactions

The $\eta$-3N-interaction is studied within the four-body Faddeev-Yakubovsky theory adopting purely separable forms for the two- and three-body subamplitudes, limiting the basic two-body interactions to s-waves only. The corresponding separable approximation for the integral kernels is obtained by using the Hilbert-Schmidt procedure. Results are presented for the $\eta$-$^3$H scattering amplitude and for the total elastic cross section for energies below the triton break-up threshold.Comment: revised version accepted for Phys. Rev. C, 16 pages revtex including 6 eps-figures, formal part shortene

The nucleon-nucleon interaction

We review the major progress of the past decade concerning our understanding of the nucleon-nucleon interaction. The focus is on the low-energy region (below pion production threshold), but a brief outlook towards higher energies is also given. The items discussed include charge-dependence, the precise value of the $\pi NN$ coupling constant, phase shift analysis and high-precision NN data and potentials. We also address the issue of a proper theory of nuclear forces. Finally, we summarize the essential open questions that future research should be devoted to.Comment: 42 pages, 12 figures, iopart.cls style; Topical Review prepared for J. Phys. G: Nucl. Part. Phy

Chiral unitary approach to S-wave meson baryon scattering in the strangeness S=0 sector

We study the S-wave interaction of mesons with baryons in the strangeness S=0 sector in a coupled channel unitary approach. The basic dynamics is drawn from the lowest order meson baryon chiral Lagrangians. Small modifications inspired by models with explicit vector meson exchange in the t-channel are also considered. In addition the pi pi N channel is included and shown to have an important repercussion in the results, particularly in the isospin 3/2 sector.Comment: 23 pages, LaTeX, 21 figure

Dynamical coupled-channel model of meson production reactions in the nucleon resonance region

A dynamical coupled-channel model is presented for investigating the nucleon resonances in the meson production reactions induced by pions and photons. The model is based on an energy-independent Hamiltonian which is derived from a set of Lagrangians by using a unitary transformation method. By applying the projection operator techniques,we derive a set of coupled-channel equations which satisfy the unitarity conditions within the channel space spanned by the considered two-particle meson-baryon states and the three-particle $\pi\pi N$ state. We present and explain in detail a numerical method based on a spline-function expansion for solving the resulting coupled-channel equations which contain logarithmically divergent one-particle-exchange driving terms resulted from the $\pi\pi N$ unitarity cut. We show that this driving term can generate rapidly varying structure in the reaction amplitudes associated with the unstable particle channels. It also has large effects in determining the two-pion production cross sections. Our results indicate that cautions must be taken to interpret the $N^*$ parameters extracted from using models which do not include $\pi\pi N$ cut effects.Comment: 73 pages, 20 figure

Intermediate mass excess of dilepton production in heavy ion collisions at BEVALAC energies

Dielectron mass spectra are examined for various nuclear reactions recently measured by the DLS collaboration. A detailed description is given of all dilepton channels included in the transport model UrQMD 1.0, i.e. Dalitz decays of $\pi^0,\eta,\omega,\eta'$ mesons and of the $\Delta(1232)$ resonance, direct decays of vector mesons and $pn$ bremsstrahlung. The microscopic calculations reproduce data for light systems fairly well, but tend to underestimate the data in $pp$ at high energies and in $pd$ at low energies. These conventional sources, however, cannot explain the recently reported enhancement for nucleus-nucleus collisions in the mass region 0.15 GeV<$M_{ee}$<0.6 GeV. Chiral scaling and $\omega$ meson broadening in the medium are investigated as a source of this mass excess. They also cannot explain the recent DLS data.Comment: 26 pages, 9 figures, references update

Electromagnetic Meson Production in the Nucleon Resonance Region

Recent experimental and theoretical advances in investigating electromagnetic meson production reactions in the nucleon resonance region are reviewed.Comment: 75 pages, 42 figure