Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.
BACKGROUNDChronic obstructive pulmonary disease (COPD) is a risk factor that increases the incidence of postoperative cardiopulmonary morbidity and mortality after lung resection. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has been reported previously to attenuate intrapulmonary shunt during one-lung ventilation (OLV) and to alleviate bronchoconstriction.OBJECTIVEThe objective is to determine whether dexmedetomidine improves oxygenation and lung mechanics in patients with moderate COPD during lung cancer surgery.DESIGNA randomised, double-blinded, placebo-controlled study.SETTINGSingle university hospital.PARTICIPANTSFifty patients scheduled for video-assisted thoracoscopic surgery who had moderate COPD. Patients were randomly allocated to a control group or a Dex group (n = 25 each).INTERVENTIONSIn the Dex group, dexmedetomidine was given as an initial loading dose of 1.0 μg kg−1 over 10 min followed by a maintenance dose of 0.5 μg kg−1 h−1 during OLV while the control group was administered a comparable volume of 0.9% saline. Data were measured at 30 min (DEX-30) and 60 min (DEX-60) after dexmedetomidine or saline administration during OLV.MAIN OUTCOME MEASURESThe primary outcome was the effect of dexmedetomidine on oxygenation. The secondary outcome was the effect of dexmedetomidine administration on postoperative pulmonary complications.RESULTSPatients in the Dex group had a significantly higher PaO2/FiO2 ratio (27.9 ± 5.8 vs. 22.5 ± 8.4 and 28.6 ± 5.9 vs. 21.0 ± 9.9 kPa, P < 0.05), significantly lower dead space ventilation (19.2 ± 8.5 vs. 24.1 ± 8.1 and 19.6 ± 6.7 vs. 25.3 ± 7.8%, P < 0.05) and higher dynamic compliance at DEX-30 and DEX-60 (P = 0.0001 and P = 0.0184) compared with the control group. In the Dex group, the PaO2/FiO2 ratio in the postoperative period was significantly higher (P = 0.022) and the incidence of ICU admission was lower than in the control group.CONCLUSIONDexmedetomidine administration may provide clinically relevant benefits by improving oxygenation and lung mechanics in patients with moderate COPD undergoing lung cancer surgery.TRIAL REGISTRATIONClinicalTrial.gov identifier: NCT 02185430.
Objective To investigate the effects of single-dose intravenous dexamethasone on inflammatory responses, pain, nausea, and vomiting after uterine artery embolisation (UAE).Design Prospective, randomised, double-blind, and placebocontrolled study.Setting Tertiary-care University centre in Korea.Population Patients undergoing UAE for the treatment of symptomatic fibroids or adenomyosis.Methods Patients were randomised to receive either intravenous dexamethasone (10 mg; dexamethasone group) or normal saline (control group) 1 hour before UAE. Both groups received fentanyl-based intravenous patient-controlled analgesia (PCA) during the 24 hours after UAE.Main outcome measures The primary outcomes were the inflammatory and stress responses measured by white blood cell count, neutrophil percentage, C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol. Secondary outcomes were severity of pain and incidence of nausea and vomiting.Results Sixty-four patients were enrolled and 59 patients completed the study. CRP, IL-6, and cortisol were significantly lower in the dexamethasone group compared with the control group during the 24 hours after UAE. Although the cumulative dose of fentanyl and additional analgesics administered during the 24 hours after UAE were similar between the two groups, pain scores were significantly lower in the dexamethasone group from 12 hours after UAE, and the incidence of severe nausea and vomiting was lower in the dexamethasone group. ConclusionsThe administration of single-dose intravenous dexamethasone as an adjunct to fentanyl-based intravenous PCA is effective in reducing inflammation and pain during the first 24 hours after UAE.
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