48 research outputs found
Interleukin(IL)-36α and IL-36γ Induce Proinflammatory Mediators from Human Colonic Subepithelial Myofibroblasts
Background: Interleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36α and IL-36Îł using human colonic subepithelial myofibroblasts (SEMFs). Methods: The mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The intracellular signaling of IL-36 cytokines was analyzed using Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88 adaptor proteins (MyD88 and IRAK1) and NF-ÎșB p65. Results: IL-36α and IL-36Îł significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1, CXCL2, and CXCL8) by SEMFs. The combination of IL-36α/Îł and IL-17A or of IL-36α/Îł and tumor necrosis factor (TNF)-α showed a synergistic effect on the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory mediators induced by IL-36α and/or IL-36Îł was significantly suppressed by transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated protein kinases (MAPKs) and siRNAs specific for NF-ÎșBp65 significantly reduced the expression of IL-6 and CXC chemokines induced by IL-36α and/or IL-36Îł. Conclusion: These results suggest that IL-36α and IL-36Îł contribute to gut inflammation through the induction of proinflammatory mediators
Comparison of intrathecal morphine with continuous patient-controlled epidural anesthesia versus intrathecal morphine alone for post-cesarean section analgesia: a randomized controlled trial
Background
Several neuraxial techniques have demonstrated effective post-cesarean section analgesia. According to previous reports, it is likely that patient-controlled epidural analgesia (PCEA) without opioids is inferior to intrathecal morphine (IM) alone for post-cesarean section analgesia. However, little is known whether adding PCEA to IM is effective or not. The aim of this study was to compare post-cesarean section analgesia between IM with PCEA and IM alone.
Methods
Fifty patients undergoing elective cesarean section were enrolled in this prospective randomized study. Patients were randomized to one of two groups: IM group and IMâ+âPCEA group. All patients received spinal anesthesia with 12âmg of 0.5% hyperbaric bupivacaine, 10âÎŒg of fentanyl, and 150âÎŒg of morphine. Patients in IMâ+âPCEA group received epidural catheterization through Th11â12 or Th12-L1 before spinal anesthesia and PCEA (basal 0.167% levobupivacaine infusion rate of 6âmL/h, bolus dose of 3âmL in lockout interval of 30âmin) was commenced at the end of surgery. A numerical rating scale (NRS) at rest and on movement at 4,8,12,24,48âh after the intrathecal administration of morphine were recorded. In addition, we recorded the incidence of delayed ambulation and the number of patients who requested rescue analgesics. We examined NRS using Bonferroniâs multiple comparison test following repeated measures analysis of variance; pâ<â0.05 was considered as statistically significant.
Results
Twenty-three patients in each group were finally analyzed. Mean NRS at rest was significantly higher in IM group than in IMâ+âPCEA group at 4 (2.7 vs 0.6), 8 (2.2 vs 0.6), and 12âh (2.5 vs 0.7), and NRS during mobilization was significantly higher in IM group than in IMâ+âPCEA group at 4 (4.9 vs 1.5), 8 (4.8 vs 1.9), 12 (4.9 vs 2), and 24âh (5.7 vs 3.5). The number of patients who required rescue analgesics during the first 24âh was significantly higher in IM group compared to IMâ+âPCEA group. No significant difference was observed between the groups in incidence of delayed ambulation.
Conclusions
The combined use of PCEA with IM provided better post-cesarean section analgesia compared to IM alone.
Trial registration
UMIN-CTR (Registration No. UMIN000032475). Registered 6 May 2018 â Retrospectively registered
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Viral VectorâMediated Gene Transfer of Glutamic Acid Decarboxylase for Chronic Pain Treatment: A Literature Review
Chronic pain is long-lasting nociceptive state, impairing the patient's quality of life. Existing analgesics are generally not effective in the treatment of chronic pain, some of which such as opioids have the risk of tolerance/dependence and overdose death with higher daily opioid doses for increasing analgesic effect. Opioid use disorders have already reached an epidemic level in the United States; therefore, nonopioid analgesic approach and/or use of nonpharmacologic interventions will be employed with increasing frequency. Viral vectorâmediated gene therapy is promising in clinical trials in the nervous system diseases. Glutamic acid decarboxylase (GAD) enzyme, a key enzyme in biosynthesis of Îł-aminobutyric acid (GABA), plays an important role in analgesic mechanism. In the literature review, we used PubMed and bioRxiv to search the studies, and the eligible criteria include (1) article written in English, (2) use of viral vectors expressing GAD67 or GAD65, and (3) preclinical pain models. We identified 13 eligible original research articles, in which the pain models include nerve injury, HIV-related pain, painful diabetic neuropathy, and formalin test. GAD expressed by the viral vectors from all the reports produced antinociceptive effects. Restoring GABA systems is a promising therapeutic strategy for chronic pain, which provides evidence for the clinical trial of gene therapy for pain in the near future
Inhibition of Mitochondrial Fission Protein Reduced Mechanical Allodynia and Suppressed Spinal Mitochondrial Superoxide Induced by Perineural Human Immunodeficiency Virus gp 120 in Rats
Anesthesia and Analgesia in Pres