Rikkunshi-to attenuates adverse gastrointestinal symptoms induced by fluvoxamine

<p>Abstract</p> <p>Background</p> <p>Upper gastrointestinal (GI) symptoms such as nausea and vomiting are common adverse events associated with selective serotonin reuptake inhibitors (SSRIs), and may result in discontinuation of drug therapy in patients with depressive disorder. Rikkunshi-to (formulation TJ-43), a traditional herbal medicine, has been reported to improve upper GI symptoms and comorbid depressive symptoms in patients with functional dyspepsia. The aim of the present study was to determine if TJ-43 reduces GI symptoms and potentiates an antidepressant effect in a randomized controlled study of depressed patients treated with fluvoxamine (FLV).</p> <p>Methods</p> <p>Fifty patients with depressive disorder (19–78 years, mean age 40.2 years) were treated with FLV (n = 25) or FLV in combination with TJ-43 (FLV+TJ-43) (n = 25) for eight weeks. The following parameters of the two groups were compared: The number of patients who complained of adverse events and their symptoms; GI symptoms quality of life (QOL) score, assessed by the Gastrointestinal Symptom Rating Scale (GSRS), Japanese edition, before and two weeks after beginning treatment; and depressive symptoms assessed by the Self-Rating Depression Scale (SDS), before and 2, 4, and 8 weeks after beginning treatment.</p> <p>Results</p> <p>The number of patients who complained of adverse events in the FLV+TJ-43 group (n = 6) was significantly lower than the number complaining in the FLV group (n = 13) (<it>P </it>< 0.05). The number of patients who complained of nausea was also lower in the FLV+TJ-43 group (n = 3) than in the FLV group (n = 9) (<it>P </it>< 0.05). By two weeks after treatment, GSRS scores had improved in the FLV+TJ-43 group, but not in the FLV group. SDS scores were not different between the two groups at any of the assessment points.</p> <p>Conclusion</p> <p>This study suggests that Rikkunshi-to reduces FLV-induced adverse events, especially nausea, and improves QOL related to GI symptoms without affecting the antidepressant effect of FLV.</p

Hybrid Element-Free Galerkin - Finite Element Method for Electromagnetic Field Analysis (in Japanese)

In this paper, a new hybrid computational procedure utilizing the element free Galerkin method (EFGM) and the finite element method (FEM) for electromagnetic field analysis is proposed. It is well known that for problems which include moving objects or objects which change their shape, such as in shape optimi-zation, the FEM is not the best solution. For such problem the FEM always requires re-meshing of a part of the entire analysis domain which is computationally very expensive. We have recently proposed a new computational approach based on the EFGM which requires only nodal and boundary condition data to solve for the unknown field. Although free of mesh generation problems, this EFGM exhibits low accuracy if the nodal disposition is not uniform, and longer computation time than the ordinary FEM. To use the advantageous of both EFG-FE method, we developed a new hybrid method. In this paper, the proposed hybrid method is verified using several examples

Suzaku diagnostics of the energetics in the lobes of the giant radio galaxy 3C 35

The Suzaku observation of a giant radio galaxy 3C 35 revealed faint extended X-ray emission, associated with its radio lobes and/or host galaxy. After careful subtraction of the X-ray and non-X-ray background and contaminating X-ray sources, the X-ray spectrum of the faint emission was reproduced by a sum of the power-law (PL) and soft thermal components. The soft component was attributed to the thermal plasma emission from the host galaxy. The photon index of the PL component, $\Gamma = 1.35_{-0.86}^{+0.56}$$_{-0.10}^{+0.11}$ where the first and second errors represent the statistical and systematic ones, was found to agree with the synchrotron radio index from the lobes, $\Gamma_{\rm R} = 1.7$. Thus, the PL component was attributed to the inverse Compton (IC) X-rays from the synchrotron electrons in the lobes. The X-ray flux density at 1 keV was derived as $13.6\pm 5.4_{-3.6}^{+4.0}$ nJy with the photon index fixed at the radio value. The X-ray surface brightness from these lobes ($\sim 0.2$ nJy arcmin$^{-2}$) is lowest among the lobes studied through the IC X-ray emission. In combination with the synchrotron radio flux density, $7.5 \pm 0.2$ Jy at 327.4 MHz, the electron energy density spatially averaged over the lobes was evaluated to be the lowest among those radio galaxies, as $u_{\rm e} = (5.8 \pm 2.3 _{-1.7}^{+1.9}) \times 10^{-14}$ ergs cm$^{-3}$ over the electron Lorentz factor of $10^{3}$ -- $10^{5}$. The magnetic energy density was calculated as $u_{\rm m}=(3.1_{-1.0}^{+2.5}$$_{-0.9}^{+1.4}) \times 10^{-14}$ ergs cm$^{-3}$, corresponding to the magnetic field strength of $0.88_{-0.16}^{+0.31}$$_{-0.14}^{+0.19}$ $\mu$G. These results suggest that the energetics in the 3C 35 lobes are nearly consistent with equipartition between the electrons and magnetic fields.Comment: 10 pages, 8 figures, accepted for Ap

Suzaku observation of the giant radio galaxy 3C 326

A Suzaku observation of a giant radio galaxy, 3C 326, which has a physical size of about 2 Mpc, was conducted on 2008 January 19 -- 21. In addition to several X-ray sources, diffuse emission was significantly detected associated with its west lobe, but the east lobe was contaminated by an unidentified X-ray source WARP J1552.4+2007. After careful evaluation of the X-ray and Non X-ray background, the 0.4 -- 7 keV X-ray spectrum of the west lobe is described by a power-law model. The photon index and 1 keV flux density was derived as $1.82_{-0.24}^{+0.26}\pm0.04$ and $19.4_{-3.2}^{+3.3}\pm 3.0$ nJy, respectively, where the first and second errors represent the statistical and systematic ones. The diffuse X-rays were attributed to be inverse Compton radiation by the synchrotron radio electrons scattering off the cosmic microwave background photons. This radio galaxy is the largest among those with lobes detected through inverse Compton X-ray emission. A comparison of the radio to X-ray fluxes yields the energy densities of electron and magnetic field as $u_e = (2.3 \pm 0.3 \pm 0.3) \times 10^{-13}$ ergs/cm3 and $u_m = (1.2_{-0.1}^{+0.2}\pm 0.2) \times 10^{-14}$ ergs/cm3, respectively. The galaxy is suggested to host a low luminosity nucleus with an absorption-corrected 2 -- 10 keV luminosity of $<2 \times 10^{42}$ ergs/s, together with a relatively weak radio core. The energetics in the west lobe of 3C 326 were compared with those of moderate radio galaxies with a size of $\sim 100$ kpc. The west lobe of 3C 326 is confirmed to agree with the correlations for the moderate radio galaxies, $u_e \propto D^{-2.2\pm0.4}$ and $u_m \propto D^{-2.4\pm0.4}$, where $D$ is their total physical size. This implies that the lobes of 3C 326 are still being energized by the jet, despite the current weakness of the nucleus.Comment: 11 pages, 10 figures, 6 tables, Accepted for ApJ (v706 issue

Universal relations in the finite-size correction terms of two-dimensional Ising models

Quite recently, Izmailian and Hu [Phys. Rev. Lett. 86, 5160 (2001)] studied the finite-size correction terms for the free energy per spin and the inverse correlation length of the critical two-dimensional Ising model. They obtained the universal amplitude ratio for the coefficients of two series. In this study we give a simple derivation of this universal relation; we do not use an explicit form of series expansion. Moreover, we show that the Izmailian and Hu's relation is reduced to a simple and exact relation between the free energy and the correlation length. This equation holds at any temperature and has the same form as the finite-size scaling.Comment: 4 pages, RevTeX, to appear in Phys. Rev. E, Rapid Communication

Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer

Watabe T., Kaneda-Nakashima K., Kadonaga Y., et al. Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer. International Journal of Molecular Sciences 25, 5667 (2024); https://doi.org/10.3390/ijms25115667.Astatine (211At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211At-labeled prostate-specific membrane antigen (PSMA) compound ([211At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [211At]PSMA-5 was administered to both normal male ICR mice (n = 85) and cynomolgus monkeys (n = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day (n = 10 per group) and 14 days (n = 5 per group). Monkeys were observed 24 h post-administration of [211At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [211At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of 211At using a cyclotron supports its applicability for clinical use

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain–truncated form (HBΔtm) of the molecule. HBuc/uc mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBΔtm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control

How is the IUGONET project using TDAS?

GEM Mini-Workshop, San Francisco; 2011-12-0