Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study

AIM:To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease(AN-PEP)to mitigate the im-munogenic effects of gluten in celiac patients.METHODS:Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet(GFD)resulting in normalised antibodies and mucosal healing classified as Marsh 0 orⅠwere included.In a randomised double-blind placebo-controlled pilot study,patients consumed toast(approximately 7 g/d gluten)with AN-PEP for 2 wk(safety phase).After a 2-wk washout period with adherence of the usual GFD,14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk(efficacy phase).Measurements at baseline included complaints,quality-of-life,serum antibodies,immunophenotyping of T-cells and duodenal mucosa immunohistology.Furthermore,serum and quality of life questionnaires were collected during and after the safety,washout and efficacy phase.Duodenal biopsies were collected after the safety phase and after the efficacy phase.A change in histological evaluation according to the modified Marsh classification was the primary endpoint.RESULTS:In total,16 adults were enrolled in the study.No serious adverse events occurred during the trial and no patients withdrew during the trial.The mean score for the gastrointestinal subcategory of the celiac disease quality(CDQ)was relatively high throughout the study,indicating that AN-PEP was well tolerated.In the efficacy phase,the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed.During the efficacy phase,neither the placebo nor the AN-PEP group developed significant antibody titers.The IgA-EM concentrations remained negative in both groups.Two patients were excluded from entering the efficacy phase as their mucosa showed an increase oftwo Marsh steps after the safety phase,yet with undetectable s     

Autistic enterocolitis: Fact or fiction?

Autism spectrum disorder refers to syndromes of varying severity, typified by impaired social interactions, communicative delays and restricted, repetitive behaviours and interests. The prevalence of autism spectrum disorders has been on the rise, while the etiology remains unclear and most likely multifactorial. There have been several reports of a link between autism and chronic gastrointestinal symptoms. Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls. Postulated mechanisms include aberrant immune responses to some dietary proteins, abnormal intestinal permeability and unfavourable gut microflora. Two autism spectrum disorder patients with chronic intestinal symptoms and abnormal endoscopic findings are described, followed by a review of this controversial topic.     

Effect of alternative photostimulable phosphor plates erasing times on subjective digital image quality

Objective

To evaluate the influence of alternative erasing times of DenOptix® (Dentsply/Gendex, Chicargo, IL) digital plates on subjective image quality and the probability of double exposure image not occurring.

Methods

Human teeth were X-rayed with phosphor plates using ten different erasing times. Two observers evaluated the images for subjective image quality (sharpness, brightness, contrast, enamel definition, dentin definition and dentin-enamel junction definition) and for the presence or absence of double exposure image. Spearman''s correlation analysis and ANOVA was performed to verify the existence of a linear association between the subjective image quality parameters and the alternative erasing times. A contingency table was constructed to evaluate the agreement among the observers, and a binominal logistic regression was performed to verify the correlation between the erasing time and the probability of double exposure image not occurring.

Results

All 6 parameters of image quality were rated high by the examiners for the erasing times between 25 s and 130 s. The same erasing time range, from 25 to 130 s, was considered a safe erasing time interval, with no probability of a double exposure image occurring.

Conclusions

The alternative erasing times from 25 s to 130 s showed high image quality and no probability of double image occurrence. Thus, it is possible to reduce the operating time of the DenOptix® digital system without jeopardizing the diagnostic task.     

The effect of aerobic exercise on treatment‐related acute toxicity in men receiving radical external beam radiotherapy for localised prostate cancer

KAPUR G., WINDSOR P.M. & Mc COWAN C. (2010) European Journal of Cancer Care 19 , 643–647 The effect of aerobic exercise on treatment‐related acute toxicity in men receiving radical external beam radiotherapy for localised prostate cancer We retrospectively analysed acute radiation toxicity data for patients who had participated in a randomised controlled study in our centre in order to assess the impact of aerobic exercise on acute rectal and bladder morbidity during treatment. Data from 65 of 66 patients were analysed: 33 allocated into a control group (standard advice) and 33 into an exercise group (aerobic walking for 30 min at least three times per week) during 4 weeks of external beam radiotherapy; one patient in the exercise group withdrew after randomisation before starting radiotherapy. There was a trend towards less severe acute rectal toxicity in the exercise group with a statistically significant difference in mean toxicity scores over the 4 weeks of radiotherapy (P = 0.004), with no significant difference in bladder toxicity scores between the two groups (P = 0.123). The lack of an association for severity of bladder toxicity could be attributed to the confounding effect of lower urinary tract symptoms from their prostate cancer. Keeping active and being asked to adhere to a well‐defined exercise schedule appears to reduce the severity of rectal toxicity during radiotherapy to the prostate.     

Mammary stem cells and cancer: roles of Wnt signaling in plain view

The likely roles of Wnt signaling in regulating mammary stem cell behavior have been much discussed, in part because they may underlie the oncogenic effects of Wnt signaling in mammary tissue. Two recent papers add important data to this field. One tests directly the effects of purified Wnt protein on mouse mammary stem cells in culture and finds a specific increase in the proportion of cells with self-renewing stem cell phenotypes. The second identifies a novel target gene of canonical Wnt signaling that may be expressed in stem cells and is induced in both mouse and human mammary tumors associated with Wnt pathway activation.     

Identification of critical regions for clinical features of distal 10q deletion syndrome

Array comparative genomic hybridization studies were performed to further characterize cytogenetic abnormalities found originally by karyotype and fluorescence in situ hybridization in five clinical cases of distal 10q deletions, including several with complex cytogenetic rearrangements and one with a partial male-to-female sex-reversal phenotype. These results have enabled us to narrow the previously proposed critical regions for the craniofacial, urogenital, and neuropsychiatric disease-related manifestations associated with distal 10q deletion syndrome. Furthermore, we propose that haploinsufficiency of the DOCK1 gene may play a crucial role in the pathogenesis of the 10q deletion syndrome. We hypothesize that alteration of DOCK1 and/or other genes involved in regulation and signaling of multiple pathways can explain the wide range of phenotypic variability between patients with similar or identical cytogenetic abnormalities.     

Intracellular sequestration of amiodarone: role of vacuolar ATPase and macroautophagic transition of the resulting vacuolar cytopathology

Background and purpose:

Tissue deposits of the anti-arrhythmic drug amiodarone are a major source of side effects (skin discoloration, etc.). We addressed the mechanism of the concentration of amiodarone in cells, and characterized the resulting vacuolar cytopathology and its evolution towards macroautophagy.

Experimental approach:

Sequestration of amiodarone in human cells (macrophages, smooth muscle cells, HEK 293a cells) was evaluated using its violet fluorescence and cytopathology using GFP-conjugated subcellular markers. Autophagic signalling was probed by immunoblotting for the effector protein LC3. A patient biopsy of amiodarone-induced blue-gray skin discoloration was investigated for the presence of macroautophagy (immunofluorescence for LC3).

Key results:

Most of the amiodarone (1–20 µM, 4–24 h) captured by cultured cells (macrophages were most avid) was present in enlarged vacuoles. The specific vacuolar ATPase (V-ATPase) inhibitors, bafilomycin A1 or {"type":"entrez-nucleotide","attrs":{"text":"FR167356","term_id":"258088392","term_text":"FR167356"}}FR167356, prevented vacuolization and drug uptake. Vacuoles in HEK 293a cells were positive for markers of late endosomes and lysosomes (GFP-Rab7, -CD63) and for an effector of macroautophagy, GFP-LC3. The vacuoles accumulated endogenous LC3 and filled with lipids (Nile red staining) following longer amiodarone treatments (≥24 h). The electrophoretic mobility of both GFP-LC3 and endogenous LC3 changed, showing activation in response to amiodarone. Paraffin tissue sections of the pigmented skin exhibited granular LC3 accumulation in superficial dermis macrophages.

Conclusion and implications:

Vacuolar sequestration of amiodarone occurs at concentrations close to therapeutic levels, is mediated by V-ATPase and evolves towards persistent macroautophagy and phospholipidosis. This cytopathology is not cell type specific, but tissue macrophages appear to be particularly susceptible.