immunostaining-for-dna-modifications-computational-analysis-confocal

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

For several decades, 5-methylcytosine (5mC) has been thought to be the only DNA modification with a functional significance in metazoans. The discovery of ...

University of Nottingham

Treatment of murine myotubes with high glucose concentrations (10 and 25 mM) stimulated protein degradation through the ubiquitin-proteasome pathway, and also caused activation (autophosphorylation) of PKR (double-stranded-RNA-dependent protein kinase) and eIF2alpha (eukaryotic initiation factor 2alpha). Phosphorylation of PKR and eIF2alpha was also seen in the gastrocnemius muscle of diabetic ob/ob mice. High glucose levels also inhibited protein synthesis. The effect of glucose on protein synthesis and degradation was not seen in myotubes transfected with a catalytically inactive variant (PKRDelta6). High glucose also induced an increased activity of both caspase-3 and -8, which led to activation of PKR, since this was completely attenuated by the specific caspase inhibitors. Activation of PKR also led to activation of p38MAPK (mitogen activated protein kinase), leading to ROS (reactive oxygen species) formation, since this was attenuated by the specific p38MAPK inhibitor SB203580. ROS formation was important in protein degradation, since it was completely attenuated by the antioxidant butylated hydroxytoluene. These results suggest that high glucose induces muscle atrophy through the caspase-3/-8 induced activation of PKR, leading to phosphorylation of eIF2alpha and depression of protein synthesis, together with PKR-mediated ROS production, through p38MAPK and increased protein degradation.

Mechanism of induction of muscle protein loss by hyperglycaemia.

Celiac disease (CD) is recognized as one of the most common and important autoimmune gastrointestinal disorders affecting children. There is evidence that a diagnosis of CD during childhood improves health outcomes. The increasing prevalence of CD is due to increased awareness of the wide range of extraintestinal symptoms associated with CD.

The changing frequency of celiac disease diagnosed at the Stollery Children's Hospital.

To assess patient and parent satisfaction with a primarily nurse- and dietitian-led celiac disease clinic in a tertiary pediatric centre.

Patient and parent satisfaction with a dietitian- and nurse- led celiac disease clinic for children at the Stollery Children's Hospital, Edmonton, Alberta.

Celiac disease (CD) is a common autoimmune disorder with an increasing prevalence, including in ethnic minorities.

Exploring anthropometric and laboratory differences in children of varying ethnicities with celiac disease.

Background. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition endorses serological diagnosis (SD) for pediatric celiac disease (CD). The objective of this study was to pilot SD and to prospectively evaluate gastrointestinal permeability and mucosal inflammation at diagnosis and after one year on the gluten-free diet (GFD). We hypothesized that SD would be associated with similar short term outcomes as ED. Method. Children, 3-17 years of age, referred for possible CD were eligible for SD given aTTG level ≥200 U/mL, confirmed by repeat aTTG and HLA haplotypes. Gastrointestinal permeability, assessed using sugar probes, and inflammation, assessed using fecal calprotectin (FC), at baseline and after one year on a GFD were compared to patients who had ED. Results. Enrolled SD (n = 40) and ED (n = 48) patients had similar demographics. ED and SD groups were not different in baseline lactulose: mannitol ratio (L : M) (0.049 versus 0.034; p = 0.07), fractional excretion of sucrose (%FES; 0.086 versus 0.092; p = 0.44), or fecal calprotectin (FC; 89.6 versus 51.4; p = 0.05). At follow-up, urine permeability improved and was similar between groups, L : M (0.022 versus 0.025; p = 0.55) and %FES (0.040 versus 0.047; p = 0.87) (p > 0.05). FC improved but remained higher in the SD group (37.1 versus 15.9; p = 0.04). Conclusion. Patients on the GFD showed improved intestinal permeability and mucosal inflammation regardless of diagnostic strategy. This prospective study supports that children diagnosed by SD have resolving mucosal disease early after commencing a GFD.

A Canadian Study toward Changing Local Practice in the Diagnosis of Pediatric Celiac Disease.

Limited pediatric data exist examining the trend and predictors of antitissue transglutaminase (atTG) normalization over time in children with celiac disease (CD). We aimed to evaluate time to normalization of atTG in children after CD diagnosis, and to assess for independent predictors affecting this duration.

Article	Year
Mechanism of induction of muscle protein loss by hyperglycaemia. Experimental cell research\| PubMed ID: 18973755	2009
The changing frequency of celiac disease diagnosed at the Stollery Children's Hospital. Canadian journal of gastroenterology = Journal canadien de gastroenterologie\| PubMed ID: 20151069	2010
Patient and parent satisfaction with a dietitian- and nurse- led celiac disease clinic for children at the Stollery Children's Hospital, Edmonton, Alberta. Canadian journal of gastroenterology = Journal canadien de gastroenterologie\| PubMed ID: 23936876	2013
Exploring anthropometric and laboratory differences in children of varying ethnicities with celiac disease. Canadian journal of gastroenterology & hepatology\| PubMed ID: 25157524	2014
A Canadian Study toward Changing Local Practice in the Diagnosis of Pediatric Celiac Disease. Canadian journal of gastroenterology & hepatology\| PubMed ID: 27446854	2016
Antitissue Transglutaminase Normalization Postdiagnosis in Children With Celiac Disease. Journal of pediatric gastroenterology and nutrition\| PubMed ID: 27906802	2017

Seema Rajani

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