Effect of Activation of the GLT-1 Transporter by a Beta-Lactam Antibiotic on Serotonin-Induced Scratching Behavior in Mice

Glutamate is believed to be the predominant excitatory neurotransmitter in the networks responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses serotonin-induced itch-related behavior (similarly to its effect on pain transmission) in mice. Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam antibiotics looks promising for the treatment of chronic itch.Як вважають, глутамат є основним збуджуючим нейротрансмітером у нейронних мережах, відповідальних за поведінкові моторні прояви при почутті свербіжу. β-лактамні антибіотики мають нейропротективні властивості, оскільки забезпечують посилену експресію глутаматного транспортера GLT-1. Ми з’ясовували, чи здатне повторне введення β-лактамного антибіотика цефтриаксону пригнічувати викликані ін’єкціями серотоніну поведінкові моторні прояви (чухальні рухи), пов’язані з індукцією почуття свербіжу (подібно до впливу цього агента на біль) у мишей. Хронічні (але не поодинокі) введення цефтриаксону викликали зменшення кількості рухів чухання. Селективний блокатор транспортера GLT-1 дигідрокаїнова кислота частково, але істотно перешкоджала цьому ефекту цефтриаксону. Наші спостереження дають підстави вважати, що активація GLT-1 β-лактамними антибіотиками є перспективним підходом у лікуванні хронічного свербіжу

Different Types of Intraoperative Hypotension and their Association with Post-Anesthesia Care Unit Recovery

Background: The underlying causative mechanism leading to intraoperative hypotension (IOH) may vary depending on the stage of anesthesia and surgery, resulting in different types of IOH. Consequently, the incidence, severity, and postoperative complications associated with IOH types may differ. This study explores the association between IOH types and post-anesthesia care unit (PACU) recovery, with a focus on duration and complications. Methods: From May 2022 to December 2022, we included 4776 consecutive surgical patients aged ≥18 who underwent elective surgery with planned overnight stays at Acibadem Altunizade Hospital and received general anesthesia. Post-induction hypotension (pIOH) was defined as a decrease in blood pressure during the first 20 minutes after anesthesia induction, while maintenance intraoperative hypotension (mIOH) referred to a decrease in blood pressure occurring after the 20th minute following induction, with or without preceding pIOH.Results: Among the included patients, 22.13% experienced IOH, with a higher prevalence observed among females. Patients with mIOH exhibited higher rates of bleeding, transfusions, hypothermia, longer stays in the PACU, and increased oxygen requirements. The duration of anesthesia did not increase the likelihood of IOH. Multivariate logistic regression analysis revealed that ephedrine usage, hypothermia, the need for additional analgesics, nausea, and vomiting were factors associated with longer PACU duration. Older patients (≥65), patients with ASA≥2 status, those undergoing major surgery, experiencing unexpected bleeding, and exhibiting hypothermia at the end of anesthesia had a higher likelihood of requiring vasopressor support. Conclusions: Patients experiencing hypotension, particularly during the maintenance of anesthesia, are more prone to complications in the PACU and require closer monitoring and treatment. Although less common, mIOH has a more significant impact on outcomes compared to other factors affecting PACU recovery. The impact of mIOH on PACU duration should not be overlooked in favor of other factors. Registration: Clinicaltrials.gov identifier: NCT05671783

Characterization and life cycle assessment of geopolymer mortars with masonry units and recycled concrete aggregates assorted from construction and demolition waste

YesDeveloping a fast, cost-effective, eco-friendly solution to recycle large amounts of construction and demolition waste (CDW) generated from construction industry-related activities and natural disasters is crucial. The present investigation aims to offer a solution for repurposing CDW into building materials suitable for accelerated construction and housing in developing countries and disaster-prone areas. Feasibility of recycled concrete aggregate (RCA) inclusion in geopolymer mortars constituted entirely from CDW (masonry elements) was investigated via an environmental impact-oriented approach by addressing the composition related key parameters. Mechanical performance was evaluated through compressive strength tests, and scanning electron microscope (SEM) imaging with line mapping analyses were carried out to monitor the interfacial transition zone (ITZ) properties. To investigate the environmental impacts of the geopolymer mortars and highlight the advantages over Portland cement-based mortars, a cradle-to-gate life cycle assessment (LCA) was performed. Findings revealed that roof tile (RT)-based geopolymer mortars mainly exhibited better strength performance due to their finer particle size. Mixtures activated with 15 M NaOH solution and cured at 105 °C achieved an average compressive strength above 55 MPa. RCA size was the most influential parameter on compressive strength, and a smaller maximum RCA size significantly increased the compressive strength. Microstructural analyses showed that the ITZ around smaller RCAs was relatively thinner, resulting in better compressive strength results. LCA proved that CDW-based geopolymer mortars provide the same compressive strength with around 60% less CO2 emissions and similar energy consumption compared to Portland cement-based mortars.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 894100. The authors also wish to acknowledge the support of the Scientific and Technical Research Council of Turkey (TUBITAK) provided under project: 117M44

Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation

BACKGROUND: Spinal cord stimulation (SCS) has been shown to be effective in the management of certain neuropathic pain conditions, however, the underlying mechanisms are incompletely understood. In this study, we investigated repetitive SCS in a rodent neuropathic pain model, revealing long-lasting and incremental attenuation of hyperalgesia and a mechanism of action involving endocannabinoids. METHOD: Animals were implanted with monopolar electrodes at the time of partial sciatic nerve injury. Dorsal columns at spinal segments T12/13 were stimulated 3 days later (early SCS), and again at day 7 (late SCS) using low-frequency parameters. Hypersensitivity to cutaneous mechanical stimuli was assessed using von Frey filaments. Pharmacological agents, selected to identify endocannabinoid and opioid involvement, were administered intraperitoneally, 10 min before SCS. RESULTS: Early SCS caused partial reversal of mechanical hypersensitivity with corresponding changes in the biomarker of central sensitization, [phospho-Tyr1472 ]-GluN2B. The partial reversal of hyperalgesia by early SCS was amplified by co-administration of LY 2183240, an inhibitor of endocannabinoid reuptake/breakdown. This amplification was inhibited by a CB1 R antagonist, AM251, but not by a CB2 R antagonist, AM630. Early SCS-induced reversal of hyperalgesia was attenuated by naloxone, indicating a role for opioids. Late SCS resulted in an incremental level of reversal of hyperalgesia, which was inhibited by AM251, but not by CB2 or opioid receptor antagonists. CONCLUSION: The endocannabinoid system, and in particular the CB1 R, plays a pivotal role in the long-lasting and incremental reversal of hyperalgesia induced by repetitive SCS in a neuropathic pain model