Increased expression of transforming growth factor α precursors in acute experimental colitis in rats

Background and aim—Epidermal growth factor (EGF)and transforming growth factor α (TGF-α), members of the EGF familyof growth factors, protect rat gastric and colonic mucosa againstinjury. Having shown previously that exogenously applied EGF protects rat colonic mucosa against injury, the aim of the present study was toevaluate the endogenously expressed ligand mediating the protectiveeffect of EGF/TGF-α in vivo.
Methods—In an experimental model oftrinitrobenzene sulphonic acid (TNBS)/ ethanol induced colitis in ratsEGF and TGF-α expression was evaluated using a ribonucleaseprotection assay, northern blot analysis, western blot analysis, and immunohistochemistry.
Results—TGF-α mRNA increased 3-4 times at 4-8hours after induction of colitis and returned to control levels within24 hours. TGF-α immunoreactive protein with a molecular size of about28kDa representing TGF-α precursors increased markedly afterinduction of colitis with a peak at 8-12 hours. No fully processed 5.6 kDa TGF-α protein was detected in normal or inflamed colon tissue. Only a weak signal for EGF mRNA expression was detected in the ratcolon and no EGF protein was observed by immunohistochemistry orwestern blot analysis.
Conclusions—TGF-α precursors are the mainligands for the EGF receptor in acute colitis. It is hypothesised thatTGF-α precursors convey the biological activity of endogenous TGF-αpeptides during mucosal defence and repair.

     

Effect of rioprostil, a synthetic prostaglandin E1 on meal-stimulated gastric acid secretion and plasma gastrin levels in humans

The effects of rioprostil (a newly developed synthetic prostaglandin E1 analogue) on meal-stimulated gastric acid secretion was evaluated in 8 healthy human volunteers. Gastric acid output was measured by intragastric titration on 4 different occasions. The following procedure was invariably employed: after a basal period of 45 min, 5 peptone meals (8%, 500 ml each) were given intragastrically in 45-min intervals and gastric acid output was measured continuously. 45 min after the first meal, either placebo or 150, 300 or 600 micrograms of rioprostil were given intragastrically in a randomized order and on different days. 15 min later, the second meal was given and intragastric titration continued. Rioprostil caused a dose-dependent inhibition of the 3-hour integrated gastric acid response to the peptone meals. The percentage of inhibition was 41, 68 and 79%, respectively, for 150, 300 and 600 micrograms of rioprostil. Whereas the inhibition by the two highest doses was statistically significant, this was not the case for the lowest dose of rioprostil. The integrated 3-hour plasma gastrin response to the peptone meals was not significantly changed by any of the doses of rioprostil. No significant adverse effects were observed with rioprostil.     

Epidermal growth factor increases basal mucosal blood flow in the rat colon, a prostaglandin dependent effect

OBJECTIVE/BACKGROUND: Non-mitogenic biological activity such as modulation of mucosal blood flow is suspected to convey the protective effects of epidermal growth factor (EGF) in vivo. The aims of our present study were to determine the effects of EGF on colonic mucosal blood flow and injury induced hyperaemia in rats. DESIGN/METHODS: Rats were pretreated with i.p. injections of vehicle, EGF, or indomethacin and EGF prior to mucosal injury. Basal mucosal blood flow and injury induced hyperaemia at the border of the damaged mucosa was determined by using reflectance spectrophotometry. RESULTS: EGF significantly increased basal mucosal blood flow but did not further enhance injury induced hyperaemia. The EGF induced increase in basal mucosal blood flow was completely abolished by indomethacin pretreatment. CONCLUSIONS: EGF induces an increase of basal mucosal blood flow through induction of prostaglandin synthesis. We hypothesize that the increase in mucosal blood flow contributes to the ability of EGF to protect the colonic mucosa against injury.     

Reduced susceptibility of mice overexpressing transforming growth factor α to dextran sodium sulphate induced colitis

Background—Transforminggrowth factor α (TGF-α) knockout mice have increased susceptibilityto dextran sodium sulphate (DSS) induced colitis.
Aim—To substantiatethe findings that TGF-α is a key mediator of colonic mucosalprotection and/or repair mechanisms by evaluating the susceptibility ofmice overexpressing TGF-α to DSS induced colitis.
Methods—TGF-αoverexpression was induced in transgenic mice by ZnSO₄administration in drinking water (TG+). Three groups were used ascontrols: one transgenic group without ZnSO₄ administration (TG−), and two non-transgenic littermate groups receivingZnSO₄ (Non-TG+) or only water (Non-TG−). Acute colitiswas induced in all groups by administration of DSS (5%, w/v) indrinking water for six days ad libitum.
Results—About 35-39%of the entire colonic mucosa was destroyed in Non-TG−, Non-TG+, andTG− animals compared with 9% in TG+ mice. The crypt damage score was18.7 (0.9), 18.2 (1.0), 18.9(0.8), and 6.8 (1.5) (means (SEM)) inNon-TG−, Non-TG+, TG−, and TG+ mice respectively. Mucin andbromodeoxyuridine staining were markedly enhanced in colons of TG+ micecompared with controls, indicating increased mucosal protection and regeneration.
Conclusions—Thesignificantly reduced susceptibility of mice overexpressing TGF-α toDSS further substantiates that endogenous TGF-α is a pivotal mediatorof protection and/or healing mechanisms in the colon.

Keywords:transforming growth factor α; epidermal growthfactor; dextran sodium sulphate; colitis; inflammatory bowel disease; transgenic mice

     

Review article: A primer for clinical researchers in the emergency department: Part VI. Measuring what matters: Core outcome sets in emergency medicine research

In this series we address important topics for clinicians who participate in research as part of their work in the ED. The overarching goal of clinical research is to improve care and determine which treatment is best. Yet, defining and measuring outcomes – what is ‘best’ – can be one of the most difficult steps in the design of a study, in particular when answers to research questions cannot be captured in simple binary results. This article addresses how to choose outcome measures and highlights the increasingly important concept of core outcome sets.     

Hypervitaminosis A Inducing Intra-hepatic Cholestasis—A Rare Case Report

The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife^TM shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease.     

A cross-sectional survey of complementary and alternative medicine use by children and adolescents attending the University Hospital of Wales

Background  

A high prevalence of CAM use has been documented worldwide in children and adolescents with chronic illnesses. Only a small number of studies, however, have been conducted in the United Kingdom. The primary aim of this study was to examine the use of CAM by children and adolescents with a wide spectrum of acute and chronic medical problems in a tertiary children's hospital in Wales.