Critical role of interferons in gastrointestinal injury repair.

The etiology of ulcerative colitis is poorly understood and is likely to involve perturbation of the complex interactions between the mucosal immune system and the commensal bacteria of the gut, with cytokines acting as important cross-regulators. Here we use IFN receptor-deficient mice in a dextran sulfate sodium (DSS) model of acute intestinal injury to study the contributions of type I and III interferons (IFN) to the initiation, progression and resolution of acute colitis. We find that mice lacking both types of IFN receptors exhibit enhanced barrier destruction, extensive loss of goblet cells and diminished proliferation of epithelial cells in the colon following DSS-induced damage. Impaired mucosal healing in double IFN receptor-deficient mice is driven by decreased amphiregulin expression, which IFN signaling can up-regulate in either the epithelial or hematopoietic compartment. Together, these data underscore the pleiotropic functions of IFNs and demonstrate that these critical antiviral cytokines also support epithelial regeneration following acute colonic injury.

Real-time 2-5A kinetics suggest that interferons ß and λ evade global arrest of translation by RNase L.

Cells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate a ubiquitously expressed pseudokinase/endoribonuclease RNase L. RNase L executes regulated RNA decay and halts global translation. Here, we developed a biosensor for 2',5'-oligoadenylate (2-5A), the natural activator of RNase L. Using this biosensor, we found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular RNA cleavage by RNase L and arrested host protein synthesis. However, translation-arrested cells still transcribed IFN-stimulated genes and secreted IFNs of types I and III (IFN-ß and IFN-λ). Our data suggest that IFNs escape from the action of RNase L on translation. We propose that the 2-5A/RNase L pathway serves to rapidly and accurately suppress basal protein synthesis, preserving privileged production of defense proteins of the innate immune system.

Nonopioid (Dexmedetomidine, Dexamethasone, Magnesium) Adjuvant to Ropivacaine Caudal Anesthesia in Pediatric Patients Undergoing Infraumbilical Surgeries: A Comparative Study.

BACKGROUND: Desirable adjuvants to caudal ropivacaine are the one which prolongs analgesia and free of side effects. We compared nonopioid drugs dexmedetomidine, dexamethasone, and magnesium as adjuvants to ropivacaine caudal analgesia in pediatric patients undergoing infraumbilical surgeries. MATERIALS AND METHODS: This study was done on 128 pediatric patients (3-12-year olds) undergoing infraumbilical surgeries; they were randomly allocated to four groups to receive normal saline, dexmedetomidine 1 µg/kg, dexamethasone 0.1 mg/kg, and magnesium sulfate 50 mg with injection ropivacaine 0.2% in the dose 0.5 ml/kg caudally. Modified Objective Pain Score and Ramsay Sedation Score, duration of analgesia, hemodynamic changes, and side effects were assessed. ANOVA test was used for numerical values as data were expressed in mean and standard deviation. Kruskal-Wallis test was used for postoperative pain and sedation score as data were expressed as median and range. RESULTS: The demographic data and hemodynamics were comparable. There was a significant prolongation of duration of analgesia in all study groups, dexmedetomidine (406.2 ± 45.5 min), dexamethasone (450.0 ± 72.6 min), and magnesium (325.0 ± 45.8 min) as compared to ropivacaine (285.9 ± 52.7 min) group. None of the adjuvants resulted in either excess or prolonged sedation. No side effects were encountered. CONCLUSION: The adjuvants dexmedetomidine, dexamethasone, and magnesium added to ropivacaine prolong caudal analgesic duration without any sedation or side effect.

Comparing the Efficacy of Caudal with Intravenous Dexamethasone in the Management of Pain Following Lumbosacral Spine Surgeries: A Randomized Double Blinded Controlled Study.

BACKGROUND: The challenge in providing analgesia for spine surgeries is to provide extended postoperative pain relief and simultaneously allow early neurological assessment and mobilization. Our study aimed to evaluate the analgesic efficacy of intravenous versus caudal dexamethasone in lumbosacral spine surgeries. MATERIALS AND METHODS: In this prospective double-blind study, a total of 96 patients undergoing lumbosacral spine surgery were randomized into three groups to receive 25 ml of preemptive caudal epidural injection of either injection ropivacaine 0.2% (Group A, n = 32), a 25 ml of injection ropivacaine 0.2%, and intravenous injection dexamethasone 8 mg (Group B, n = 32) or 25 ml mixture of injection ropivacaine 0.2% with injection dexamethasone 8 mg (Group C, n = 32) under general anesthesia. Visual analog scale (VAS), heart rate, blood pressures, blood sugar levels, and time to rescue analgesia were recorded at regular intervals for the first 24 h. Time to discharge was noted. Analysis of variance has been used to find the significance of study parameters between the groups of patients. Statistical software, namely, SAS 9.2 and SPSS 15.0, have been used for the analysis of the data. RESULTS: The mean VAS was significantly lower in the Group C for up to 24 h following the caudal block. No significant hemodynamic changes were noted in any of the groups. The intravenous dexamethasone group showed higher blood glucose levels at 24 h but was not clinically relevant. CONCLUSION: These results suggest that injection dexamethasone is a safe adjunct to caudal ropivacaine in lumbosacral spine surgeries.