Effect of a selective GABAB receptor agonist, baclofen, on the opioid-induced antinociception and rewarding effect

The management of excessive adverse effects is a major clinical problem. Multiple approaches have been described to address this problem. Successful pain management with opioids required the adequate analgesia without excessive side effects. The present study was designed to investigatethe effect of a selective GABAB receptor agonist baclofen on the opioid induced antinociception and rewarding effect. In the present study, we confirmed that either morphine or fentanyl produced a dose dependent antinociceptive effect in mice using tail-flick test. The results demonstratedthat co-administration of baclofen with morphine, fentanyl or oxycodone produced the synergistic effect on antinociception in mice. In the place preference study, we found that baclofen inhibited on morphine or fentanylinduced place preference in rats. These results suggest that coadministrationof baclofen with opioids produce synergistic antinociception with less effects of place preference We propose here that co-administration of baclofen with opioids may pave the way for the new strategy for the control of pain and recommended for the adjuvant drug.Key words : opioid, place preference, rewarding effects, baclofe

<ORIGINAL ARTICLE>Histologic investigation of tissue surrounding bone in a HA-coated implant supported super structure with and without stress-absorbing elements

The effectiveness of the implant-supported overdentures has been attracted attention for edentulous patients, and a number of studies have been reported. Implant-supported overdentures refer to implant-retained tissue-borne overdentures and it is different from the implant-supported fixed partial dentures recommended by Branemark. In implant-supported overdentures, the functional load may concentrate on implant where there is rigid connection. Loaded implants may cause a resorption of surrounding bone, leading to malfunction, loosing, and the ultimate failure of the implant. The present study reports a stress-absorbing element using a resilient compound designed as the super structure of a two-piece titanium core with hydroxyapatite coated cylinder implants, to avoid stress concentrations, and a histological comparison of the surrounding bone tissue with rigid elements. No notable histological differences were observed in the trabecular patterns by contact microradiography and light microscopy

CO Multi-line Imaging of Nearby Galaxies (COMING). IX. 12^{12}CO(JJ=2-1)/12^{12}CO(JJ=1-0) line ratio on kiloparsec scales

While molecular gas mass is usually derived from $^{12}$CO($J$=1-0) - the most fundamental line to explore molecular gas - it is often derived from $^{12}$CO($J$=2-1) assuming a constant $^{12}$CO($J$=2-1)/$^{12}$CO($J$=1-0) line ratio ($R_{2/1}$). We present variations of $R_{2/1}$ and effects of the assumption that $R_{2/1}$ is a constant in 24 nearby galaxies using $^{12}$CO data obtained with the Nobeyama 45-m radio telescope and IRAM 30-m telescope. The median of $R_{2/1}$ for all galaxies is 0.61, and the weighted mean of $R_{2/1}$ by $^{12}$CO($J$=1-0) integrated-intensity is 0.66 with a standard deviation of 0.19. The radial variation of $R_{2/1}$ shows that it is high (~0.8) in the inner ~1 kpc while its median in disks is nearly constant at 0.60 when all galaxies are compiled. In the case that the constant $R_{2/1}$ of 0.7 is adopted, we found that the total molecular gas mass derived from $^{12}$CO($J$=2-1) is underestimated/overestimated by ~20%, and at most by 35%. The scatter of a molecular gas surface density within each galaxy becomes larger by ~30%, and at most by 120%. Indices of the spatially resolved Kennicutt-Schmidt relation by $^{12}$CO($J$=2-1) are underestimated by 10-20%, at most 39% in 17 out of 24 galaxies. $R_{2/1}$ has good positive correlations with star-formation rate and infrared color, and a negative correlation with molecular gas depletion time. There is a clear tendency of increasing $R_{2/1}$ with increasing kinetic temperature ($T_{\rm kin}$). Further, we found that not only $T_{\rm kin}$ but also pressure of molecular gas is important to understand variations of $R_{2/1}$. Special considerations should be made when discussing molecular gas mass and molecular gas properties inferred from $^{12}$CO($J$=2-1) instead of $^{12}$CO($J$=1-0).Comment: 29 pages, 18 figures, 5 tables. Accepted for publication in PASJ. The original resolution version is available here (https://astro3.sci.hokudai.ac.jp/~radio/coming/publications/COMING_IX_org_res.pdf

Successful Surgical Treatment of a Spontaneous Rupture of the Esophagus Diagnosed Two Days after Onset

Esophageal perforation is a relatively uncommon disease with a high rate of mortality and morbidity. Delay in the diagnosis and treatment occurs in more than 50% of cases, leading to a mortality rate of 40–60%. Primary repair is generally considered the gold standard for patients who present within the first 24 h following perforation of the esophagus. In this paper, we present a case of successful surgical treatment of spontaneous rupture of the esophagus that was diagnosed 2 days after onset. The patient was a 42-year-old man admitted to internal medicine with a diagnosis of pleuritis and complaining of chest and back pain. The next day, computed tomography revealed left-sided pleural effusion and mediastinal emphysema. An esophagogram revealed extravasation of the contrast medium from the lower left esophagus to the mediastinal cavity. These results confirmed a rupture of the esophagus, and an emergency left thoracotomy was performed. The perforation was repaired with a single-layered closure and was covered with elevated great omentum obtained by laparotomy. The patient was discharged 23 days after the first surgery. In conclusion, primary repair surgery must be selected as the best treatment beyond 24 h if the patient's general state was stable and there was no evidence of clinical sepsis

CO Multi-line Imaging of Nearby Galaxies (COMING). III. Dynamical effect on molecular gas density and star formation in the barred spiral galaxy NGC 4303

We present the results of $^{12}$CO($J$=1-0) and $^{13}$CO($J$=1-0) simultaneous mappings toward the nearby barred spiral galaxy NGC 4303 as a part of the CO Multi-line Imaging of Nearby Galaxies (COMING) project. Barred spiral galaxies often show lower star-formation efficiency (SFE) in their bar region compared to the spiral arms. In this paper, we examine the relation between the SFEs and the volume densities of molecular gas $n(\rm{H}_2)$ in the eight different regions within the galactic disk with CO data combined with archival far-ultraviolet and 24 $\mu$m data. We confirmed that SFE in the bar region is lower by 39% than that in the spiral arms. Moreover, velocity-alignment stacking analysis was performed for the spectra in the individual regions. The integrated intensity ratios of $^{12}$CO to $^{13}$CO ($R_{12/13}$) range from 10 to 17 as the results of stacking. Fixing a kinetic temperature of molecular gas, $n(\rm{H}_2)$ was derived from $R_{12/13}$ via non-local thermodynamic equilibrium (non-LTE) analysis. The density $n(\rm{H}_2)$ in the bar is lower by 31-37% than that in the arms and there is a rather tight positive correlation between SFEs and $n(\rm{H}_2)$, with a correlation coefficient of $\sim 0.8$. Furthermore, we found a dependence of $n(\rm{H}_2)$ on the velocity dispersion of inter-molecular clouds ($\Delta V/ \sin i$). Specifically, $n(\rm{H}_2)$ increases as $\Delta V/ \sin i$ increases when $\Delta V/ \sin i < 100$ km s$^{-1}$. On the other hand, $n(\rm{H}_2)$ decreases as $\Delta V/ \sin i$ increases when $\Delta V/ \sin i > 100$ km s$^{-1}$. These relations indicate that the variations of SFE could be caused by the volume densities of molecular gas, and the volume densities could be governed by the dynamical influence such as cloud-cloud collisions, shear and enhanced inner-cloud turbulence.Comment: 15 pages, 8 figures, accepted for publication in PAS

EMPRESS. IX. Extremely Metal-Poor Galaxies are Very Gas-Rich Dispersion-Dominated Systems: Will JWST Witness Gaseous Turbulent High-z Primordial Galaxies?

We present kinematics of 6 local extremely metal-poor galaxies (EMPGs) with low metallicities ($0.016-0.098\ Z_{\odot}$) and low stellar masses ($10^{4.7}-10^{7.6} M_{\odot}$). Taking deep medium-high resolution ($R\sim7500$) integral-field spectra with 8.2-m Subaru, we resolve the small inner velocity gradients and dispersions of the EMPGs with H$\alpha$ emission. Carefully masking out sub-structures originated by inflow and/or outflow, we fit 3-dimensional disk models to the observed H$\alpha$ flux, velocity, and velocity-dispersion maps. All the EMPGs show rotational velocities ($v_{\rm rot}$) of 5--23 km s$^{-1}$ smaller than the velocity dispersions ($\sigma_{0}$) of 17--31 km s$^{-1}$, indicating dispersion-dominated ($v_{\rm rot}/\sigma_{0}=0.29-0.80<1$) systems affected by inflow and/or outflow. Except for two EMPGs with large uncertainties, we find that the EMPGs have very large gas-mass fractions of $f_{\rm gas}\simeq 0.9-1.0$. Comparing our results with other H$\alpha$ kinematics studies, we find that $v_{\rm rot}/\sigma_{0}$ decreases and $f_{\rm gas}$ increases with decreasing metallicity, decreasing stellar mass, and increasing specific star-formation rate. We also find that simulated high-$z$ ($z\sim 7$) forming galaxies have gas fractions and dynamics similar to the observed EMPGs. Our EMPG observations and the simulations suggest that primordial galaxies are gas-rich dispersion-dominated systems, which would be identified by the forthcoming James Webb Space Telescope (JWST) observations at $z\sim 7$.Comment: Submitted to ApJ; After revisio

Replication of Epstein-Barr Virus Primary Infection in Human Tonsil Tissue Explants

Epstein-Barr virus (EBV) may cause a variety of virus-associated diseases, but no antiviral agents have yet been developed against this virus. Animal models are thus indispensable for the pathological analysis of EBV-related infections and the elucidation of therapeutic methods. To establish a model system for the study of EBV infection, we tested the ability of B95–8 virus and recombinant EBV expressing enhanced green fluorescent protein (EGFP) to replicate in human lymphoid tissue. Human tonsil tissues that had been surgically removed during routine tonsillectomy were sectioned into small blocks and placed on top of collagen sponge gels in culture medium at the air-interface, then a cell-free viral suspension was directly applied to the top of each tissue block. Increasing levels of EBV DNA in culture medium were observed after 12–15 days through 24 days post-infection in tissue models infected with B95–8 and EGFP-EBV. Expression levels of eight EBV-associated genes in cells collected from culture medium were increased during culture. EBV-encoded small RNA-positive cells were detected in the interfollicular areas in paraffin-embedded sections. Flow cytometric analyses revealed that most EGFP+ cells were CD3− CD56− CD19+ HLA-DR+, and represented both naïve (immunoglobulin D+) and memory (CD27+) B cells. Moreover, EBV replication in this model was suppressed by acyclovir treatment in a dose-dependent manner. These data suggest that this model has potential for use in the pathological analysis of local tissues at the time of primary infection, as well as for screening novel antiviral agents