Evidence for Inhibitory Effects of Flupirtine, a Centrally Acting Analgesic, on Delayed Rectifier K+ Currents in Motor Neuron-Like Cells

Flupirtine (Flu), a triaminopyridine derivative, is a centrally acting, non-opiate analgesic agent. In this study, effects of Flu on K+ currents were explored in two types of motor neuron-like cells. Cell exposure to Flu decreased the amplitude of delayed rectifier K+ current (IK(DR)) with a concomitant raise in current inactivation in NSC-34 neuronal cells. The dissociation constant for Flu-mediated increase of IK(DR) inactivation rate was about 9.8 μM. Neither linopirdine (10 μM), NMDA (30 μM), nor gabazine (10 μM) reversed Flu-induced changes in IK(DR) inactivation. Addition of Flu shifted the inactivation curve of IK(DR) to a hyperpolarized potential. Cumulative inactivation for IK(DR) was elevated in the presence of this compound. Flu increased the amplitude of M-type K+ current (IK(M)) and produced a leftward shift in the activation curve of IK(M). In another neuronal cells (NG108-15), Flu reduced IK(DR) amplitude and enhanced the inactivation rate of IK(DR). The results suggest that Flu acts as an open-channel blocker of delayed-rectifier K+ channels in motor neurons. Flu-induced block of IK(DR) is unlinked to binding to NMDA or GABA receptors and the effects of this agent on K+ channels are not limited to its action on M-type K+ channels

First‐line antibiotic treatment in patients with localized extragastric mucosa‐associated lymphoid tissue lymphoma

Abstract Between January 2010 and December 2015, we enrolled 28 patients with stage IEI/IIE1 extragastric mucosa‐associated lymphoid tissue (MALT) lymphoma who received first‐line antibiotic treatment, after informing them about the pros and cons of alternative therapies. In addition, during the same period, 64 patients with stage IE/IIE1 disease who received conventional treatment were selected as the control group. The most common primary sites were the ocular adnexal area (17 cases), followed by the salivary glands (four cases), pulmonary (three cases), and thyroid, trachea, larynx, and colon region (one case each). First‐line antibiotic treatment resulted in an overall response rate of 57.1%: 12 patients achieved complete remission (CR), while four achieved partial remission (antibiotic‐responsive tumors). Monoclonal gammopathy was significantly prevalent in antibiotic‐unresponsive tumors than in antibiotic‐responsive tumors (50.0% [6/12] vs. 12.5% [2/16], p = 0.044). After a median follow‐up of 7 years, all patients with CR remained lymphoma‐free, with 7‐year event‐free survival (EFS) and overall survival (OS) rates of 62.7% and 96.4%, respectively. The 7‐year EFS and OS rates of patients who received conventional treatments were 73.1% and 91.1%, respectively. Compared with that noted in patients who received conventional treatment, antibiotic treatment was effective in some patients with localized extragastric MALT lymphoma

Mirtazapine Inhibits Tumor Growth via Immune Response and Serotonergic System

<div><p>To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/<em>luc</em> colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. <em>wild-type</em> (no drug) and <em>drug</em> (mirtazapine), and four groups with tumors, i.e. <em>never</em> (no drug), <em>always</em> (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment), <em>concurrent</em> (simultaneously tumor inoculation and drug treatment throughout the experiment), and <em>after</em> (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment). The “psychiatric” conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interlukin-12 (sIL-12) and the inhibition of tumor growth were found in mirtazapine-treated mice (<em>always</em>, <em>concurrent</em>, and <em>after</em>) as compared with that of <em>never</em>. In addition, interferon-γ level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of <em>never.</em> Tumor necrosis factor-α (TNF-α) expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of <em>never</em>. Ex vivo autoradiography with [¹²³I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/<em>luc</em> colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level.</p> </div