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Abstract Background Helicobacter pylori, the main cause of various gastric diseases, infects approximately half of the human population. This pathogen is auxotrophic for cholesterol which it converts to various cholesteryl α-glucoside derivatives, including cholesteryl 6’-acyl α-glucoside (CAG). Since the related biosynthetic enzymes can be translocated to the host cells, the acyl chain of CAG likely comes from its precursor phosphatidylethanolamine (PE) in the host membranes. This work aims at examining how the acyl chain of CAG and PE inhibits the membrane functions, especially bacterial adhesion. Methods Eleven CAGs that differ in acyl chains were used to study the membrane properties of human gastric adenocarcinoma cells (AGS cells), including lipid rafts clustering (monitored by immunofluorescence with confocal microscopy) and lateral membrane fluidity (by the fluorescence recovery after photobleaching). Cell-based and mouse models were employed to study the degree of bacterial adhesion, the analyses of which were conducted by using flow cytometry and immunofluorescence staining, respectively. The lipidomes of H. pylori, AGS cells and H. pylori–AGS co-cultures were analyzed by Ultraperformance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) to examine the effect of PE(10:0)2, PE(18:0)2, PE(18:3)2, or PE(22:6)2 treatments. Results CAG10:0, CAG18:3 and CAG22:6 were found to cause the most adverse effect on the bacterial adhesion. Further LC–MS analysis indicated that the treatment of PE(10:0)2 resulted in dual effects to inhibit the bacterial adhesion, including the generation of CAG10:0 and significant changes in the membrane compositions. The initial (1 h) lipidome changes involved in the incorporation of 10:0 acyl chains into dihydro- and phytosphingosine derivatives and ceramides. In contrast, after 16 h, glycerophospholipids displayed obvious increase in their very long chain fatty acids, monounsaturated and polyunsaturated fatty acids that are considered to enhance membrane fluidity. Conclusions The PE(10:0)2 treatment significantly reduced bacterial adhesion in both AGS cells and mouse models. Our approach of membrane remodeling has thus shown great promise as a new anti-H. pylori therapy. Graphical Abstract

This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration‐dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED50; median effective dose) was epinephrine [0.013 (0.012–0.014) μmol] > oxymetazoline [0.25 (0.22–0.28) μmol] > naphazoline [0.42 (0.34–0.53) μmol] = bupivacaine [0.43 (0.37–0.50) μmol] > xylometazoline [1.34 (1.25–1.45) μmol] > lidocaine [5.86 (5.11–6.72) μmol] > tetrahydrozoline [6.76 (6.21–7.36) μmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED25, ED50, and ED75). Co‐administration of lidocaine (ED50) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co‐administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine. [ABSTRACT FROM AUTHOR]

This present study was undertaken to determine whether beta-blockers produce the cutaneous analgesic effect, comparing them with the long-acting local anesthetic bupivacaine. Using a rat model of infiltrative cutaneous analgesia, the effect of 5 beta-blockers (oxprenolol, carteolol, butaxamine, metoprolol, and acebutolol) and bupivacaine was compared and eventually combined with epinephrine. Among 5 beta-blockers, oxprenolol exhibited the most potent and the longest duration of cutaneous analgesia. In dose-response studies, the rank order of efficacy (ED50 [50% effective dose]) was bupivacaine (0.40 [0.35–0.47] μmol) > oxprenolol (2.33 [2.06–2.64] μmol) > carteolol (4.86 [4.27–5.53] μmol) (p< 0.01). Carteolol provoked a longer duration of analgesia (p< 0.01) than oxprenolol or bupivacaine on an equipotent basis (ED25, ED50, and ED75). Adding epinephrine 1:200,000 to drug preparations (carteolol, oxprenolol, and bupivacaine) at ED95 had a peripheral action in prolonging the duration of action. Oxprenolol and carteolol had greater potencies and longer durations of cutaneous analgesia than butaxamine, metoprolol, and acebutolol. Oxprenolol produced a similar duration of action when compared to bupivacaine, while carteolol had a greater duration of action than bupivacaine. Cutaneous analgesia of oxprenolol (or carteolol) plus adrenaline was greater than that of bupivacaine plus adrenaline. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of the experiment was to study the effect of L-NAME (N(Omega)-nitro-L-arginine methyl ester) and its cotreatment with lidocaine on the spinal block and infiltrative cutaneous analgesia. Methods: The quality of cutaneous analgesia was examined by the block of the cutaneous trunci muscle reflexes following needle stimuli in the rat. Spinal anaesthetic potency was assessed by measuring three neurobehavioral examinations of nociceptive, proprioceptive and motor function following intrathecal injection in the rat. Key findings: L-NAME (0.6, 6 and 60 nmol) when cotreatment with lidocaine (ED50) produced dose-related cutaneous analgesia. Coadministration of L-NAME (0.6 μmol) with lidocaine intensified (P < 0.01) and prolonged (P < 0.001) cutaneous analgesia, whereas subcutaneous L-NAME (0.6 μmol) and saline did not provoke cutaneous analgesic effects. Adding L-NAME (2.5 μmol) to lidocaine intrathecally prolonged spinal sensory and motor block (P < 0.01), while intrathecal L-NAME (2.5 μmol) or 5% dextrose (vehicle) produced no spinal block. Conclusions: L-NAME at 60 nmol (the minimum effective dose) increases and prolongs the effect of cutaneous analgesia of lidocaine. L-NANE at an ineffective dose potentiates lidocaine analgesic and anaesthetic effects. [ABSTRACT FROM AUTHOR]

Introduction: Mass casualty incident (MCI) management was usually taught by lectures and then tested by exercises. However, the lecture may not be interesting and tabletop exercise (TTx) may not adequately engage participants, especially senior medical students. To solve these two problems, we think that a TTx using 3D models can be a good teaching method of MCI management for medical students. Method: A TTx of MCI in the emergency room (ER) was designed for senior medical students based on five core capabilities of MCI management: incident management system, event recognition and initiation of response, patient triage, surge capacity and capability, and recovery and demobilization. 3D models containing miniatures of the ER, hospital staff, patients, and other personnel were used in the TTx. No lecture was conducted before or during the exercise. Students needed to discuss how to respond to events in the incident and show their responses using the 3D models, and the instructor facilitated the discussion and gave feedback right after the students' decision. Knowledge of each core capability was tested by four multiple-choice questions. The interest in learning disaster medicine and willingness to participate in MCI management were evaluated by questionnaire, along with quantitative feedback to the exercise. The same test and questionnaire were conducted before and after the TTx. Results: From September 2018 to May 2022, 326 students completed both pre- and post-exercise evaluations. The test scores of all five core capabilities, levels of interest, and willingness increased significantly after the exercise. Students thought the exercise was interesting and a good learning tool. Most students wanted to be notified of further training. Conclusion: A tabletop exercise using 3D models is an effective way to teach senior medical students MCI management and disaster medicine while increasing their interest in learning and willingness to participate. [ABSTRACT FROM AUTHOR]