Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy

Autophagy is a degradation process that acts in response to environmental stressors. Recently, autophagy has been detected in normal term, preeclamptic and intrauterine growth-restricted placentas. The object of this work was to investigate the presence of autophagy in first trimester voluntary interruption of pregnancy placental villi by the expression of autophagy-related proteins, light chain 3 (LC3), and Beclin-1. In first trimester placental villi laser scanning confocal microscopy (LSCM) analysis revealed LC3 and Beclin-1 immunoreactivity prevalently located in villous cytotrophoblasts. Using LSCM, LC3, and Beclin-1 were localized to the cytoplasm of the trophoblast layer in human full-term placentas. Beclin-1 expression and LC3 activation were confirmed by western blotting. These data emphasize that autophagy activation is different among cytotrophoblasts and syncytiotrophoblasts depending on the gestational age and thus we speculate that autophagy might play a prosurvival role throughout human pregnancy

European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations

Introduction: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. Methods: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. Results: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. Conclusion: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Review article: Biological agents in the treatment of Crohn's disease

The main aim of the management of Crohn's disease is to reduce inflammation. Current approaches with corticosteroids, immunosuppressive agents, mesalazine and antibiotics have limited therapeutic benefit for many patients. Considerable progress has been made with regard to our knowledge of the basic mechanisms of the disease, which is associated with immunological imbalance characterized by an excess of pro-inflammatory cytokines. Recent advances in bio-technology have led to the development of many new therapeutic agents, so-called biological agents, which selectively target single key processes involved in the pathogenesis of the disease. A growing number of biological agents are under investigation in both randomized controlled trials and uncontrolled studies. The aim of this review is to provide the clinician with an insight into the randomized controlled trials published in the literature on the use of biological agents in the treatment of Crohn's disease

Retrospective study recommends endoscopy when diagnosing lymphocytic colitis or eosinophilic gastrointestinal disorder in children with abdominal pain

Aim: This study assessed the prevalence, clinical presentation and outcome of lymphocytic colitis (LC) and eosinophilic gastrointestinal disease (EGID) in children with severe, recurrent abdominal pain (RAP), by describing the predominant symptoms, diagnostic approaches and treatment options. Methods: We performed a retrospective follow-up study at a Danish regional hospital by reviewing the histology reports of the children who had undergone gastrointestinal endoscopy for RAP. Data were retrieved from the medical records of those who met the diagnostic criteria for LC and, or, EGID from 2011 to 2016. The study population comprised 381 patients who underwent a diagnostic process to clarify RAP. Results: A total of 74 patients (39 females) aged 2–17 years, with severe RAP as the most predominant symptom underwent gastrointestinal endoscopy. This identified 16/74 (21.6%) with LC (n = 6) and, or, EGID (n = 11), which equated to 4.2% with RAP. No biochemical patterns of abnormalities were found. Medical treatment and, or, diet generally induced and maintained clinical remission. Conclusion: We found 16 children with LC and, or, EGID. The predominant symptom was severe RAP. All patients had a macroscopically normal mucosa at endoscopy, a specific histopathological feature and no characteristic biochemical findings. Endoscopy should be considered in these cases.</p

Effect of infliximab on small bowel stenoses in patients with Crohn's disease

AIM: To assess prospectively small bowel stenoses in Crohn's disease (CD) patients treated with infliximab using Small Intestine Contrast Ultrasonography (SICUS). METHODS: Twenty patients (M 12, age, 42.7 +/- 11.8 years), 15 of whom showed obstructive symptoms indicating the presence of small bowel stenosis, and 5 without stenosis, were treated with infliximab (5 mg/kg at A 0, 2, 6 and 5 mg/kg every 8 A thereafter) for steroid refractoriness, fistulizing disease, or to avoid high-risk surgery. SICUS was performed at the induction phase and at regular time intervals during the follow-up period of 34.7 +/- 16.1 mo (range 7-58). Small bowel stenoses were detected by SICUS, endoscopy and MRI. RESULTS: In no case was progression of stenoses or the appearance of new ones seen. Of the 15 patients with stenosis, 5 stopped treatment after the induction phase (2 for no response, 3 for drug intolerance, one of whom showed complete regression of one stenosis). Among the remaining 10 patients, a complete regression of 8 stenoses (1 stenosis in 5 patients and 3 stenoses in one patient) was observed after 6-22 infliximab infusions. CONCLUSION: In patients with CD treated with infliximab we observed: (a) No progression of small bowel stenosis and no appearance of new ones, (b) Complete regression of 1/22 stenosis after the induction phase and of 8/15 (53.3%) stenosis after 6-22 infusions during maintenance therapy. (c) 2008 WJG. All rights reserved