Colonic dysmotility associated with high-fat diet-induced obesity: Role of enteric glia
FASEB JOURNAL
Authors: Antonioli, Luca; D'Antongiovanni, Vanessa; Pellegrini, Carolina; Fornai, Matteo; Benvenuti, Laura; di Carlo, Alma; van den Wijngaard, Rene; Caputi, Valentina; Cerantola, Silvia; Giron, Maria Cecilia; Nemeth, Zoltan H.; Hasko, Gyorgy; Blandizzi, Corrado; Colucci, Rocchina
Abstract
The present study was designed to examine the role of enteric glial cells (EGCs) in colonic neuromuscular dysfunctions in a mouse model of high-fat diet (HFD)-induced obesity. C57BL/6J mice were fed with HFD or standard diet (SD) for 1, 2, or 8 weeks. Colonic interleukin (IL)-1 beta, IL-6, and malondialdehyde (MDA) levels were measured. Expression of occludin in colonic tissues was examined by western blot. Substance P (SP), S100 beta, GFAP, and phosphorylated mitogen-activated protein kinase 1 (pERK) were assessed in whole mount specimens of colonic plexus by immunohistochemistry. Colonic tachykininergic contractions, elicited by electrical stimulation or exogenous SP, were recorded in the presence or absence of fluorocitrate (FC). To mimic exposure to HFD, cultured EGCs were incubated with palmitate (PA) and/or lipopolysaccharide (LPS). SP and IL-1 beta levels were assayed in the culture medium by ELISA. HFD mice displayed an increase in colonic IL-1 beta and MDA, and a reduction of occludin at week 2. These changes occurred to a greater extent at week 8. In vitro electrically evoked tachykininergic contractions were enhanced in HFD mice after 2 or 8 weeks, and they were blunted by FC. Colonic IL-6 levels as well as substance P and S100 beta density in myenteric ganglia of HFD mice were increased at week 8, but not at week 1 or 2. In cultured EGCs, co-incubation with palmitate plus LPS led to a significant increase in both SP and IL-1 beta release. HFD-induced obesity is characterized by a hyperactivation of EGCs and is involved in the development of enteric motor disorders through an increase in tachykininergic activity and release of pro-inflammatory mediators.
Validation of the scandinavian guidelines for initial management of minor and moderate head trauma in children
EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY
Authors: Sonnerqvist, Caroline; Brus, Ole; Olivecrona, Magnus
Abstract
Background Head trauma in children is common, with a low rate of clinically important traumatic brain injury. CT scan is the reference standard for diagnosis of traumatic brain injury, of which the increasing use is alarming because of the risk of induction of lethal malignancies. Recently, the Scandinavian Neurotrauma Committee derived new guidelines for the initial management of minor and moderate head trauma. Our aim was to validate these guidelines. Methods We applied the guidelines to a population consisting of children with mild and moderate head trauma, enrolled in the study: "Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study" by Kuppermann et al. (Lancet 374(9696):1160-1170,, 2009). We calculated the negative predictive values of the guidelines to assess their ability to distinguish children without clinically-important traumatic brain injuries and traumatic brain injuries on CT scans, for whom CT could be omitted. Results We analysed a population of 43,025 children. For clinically-important brain injuries among children with minimal head injuries, the negative predictive value was 99.8% and the rate was 0.15%. For traumatic findings on CT, the negative predictive value was 96.9%. Traumatic finding on CT was detected in 3.1% of children with minimal head injuries who underwent a CT examination, which accounts for 0.45% of all children in this group. Conclusion Children with minimal head injuries can be safely discharged with oral and written instructions. Use of the SNC-G will potentially reduce the use of CT.