132 research outputs found

    Lack of Relationship Between Chronic Upper Abdominal Symptoms and Gastric Function in Functional Dyspepsia

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    To determine the relationship between gastric function and upper abdominal sensations we studied sixty FD patients (43 female). All patients underwent three gastric function tests: 13C octanoic gastric emptying test, three-dimensional ultrasonography (proximal and distal gastric volume), and the nutrient drink test. Upper abdominal sensations experienced in daily life were scored using questionnaires. Impaired proximal gastric relaxation (23%) and a delayed gastric emptying (33%) are highly prevalent in FD patients; however, only a small overlap exists between the two pathophysiologic disorders (5%). No relationship was found between chronic upper abdominal symptoms and gastric function (proximal gastric relaxation, gastric emptying rate, or drinking capacity) (all P > 0.01). Proximal gastric relaxation or gastric emptying rate had no effect on maximum drinking capacity (P > 0.01). The lack of relationship between chronic upper abdominal sensations and gastric function questions the role of these pathophysiologic mechanisms in the generation of symptoms

    International prospective observational study investigating the disease course and heterogeneity of paediatric-onset inflammatory bowel disease: the protocol of the PIBD-SETQuality inception cohort study

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    INTRODUCTION: Patients with paediatric-onset inflammatory bowel disease (PIBD) may develop a complicated disease course, including growth failure, bowel resection at young age and treatment-related adverse events, all of which can have significant and lasting effects on the patient's development and quality of life. Unfortunately, we are still not able to fully explain the heterogeneity between patients and their disease course and predict which patients will respond to certain therapies or are most at risk of developing a more complicated disease course. To investigate this, large prospective studies with long-term follow-up are needed. Currently, no such European or Asian international cohorts exist. In this international cohort, we aim to evaluate disease course and which patients are most at risk of therapy non-response or development of complicated disease based on patient and disease characteristics, immune pathology and environmental and socioeconomic factors. METHODS AND ANALYSIS: In this international prospective observational study, which is part of the PIBD Network for Safety, Efficacy, Treatment and Quality improvement of care (PIBD-SETQuality), children diagnosed with inflammatory bowel disease <18 years are included at diagnosis. The follow-up schedule is in line with standard PIBD care and is intended to continue up to 20 years. Patient and disease characteristics, as well as results of investigations, are collected at baseline and during follow-up. In addition, environmental factors are being assessed (eg, parent's smoking behaviour, dietary factors and antibiotic use). In specific centres with the ability to perform extensive immunological analyses, blood samples and intestinal biopsies are being collected and analysed (flow cytometry, plasma proteomics, mRNA expression and immunohistochemistry) in therapy-naïve patients and during follow-up. ETHICS AND DISSEMINATION: Medical ethical approval has been obtained prior to patient recruitment for all sites. The results will be disseminated through peer-reviewed scientific publications. TRIAL REGISTRATION NUMBER: NCT03571373

    Adrenergic β2 receptor activation stimulates anti-inflammatory properties of dendritic cells in vitro

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    Vagal nerve efferent activation has been shown to ameliorate the course of many inflammatory disease states. This neuromodulatory effect has been suggested to rest on acetylcholine receptor (AChR) activation on tissue macrophages or dendritic cells (DCs). In more recent studies, vagal anti-inflammatory activity was shown involve adrenergic, splenic, pathways. Here we provide evidence that the adrenergic, rather than cholinergic, receptor activation on bone marrow derived DCs results in enhanced endocytosis uptake, enhanced IL-10 production but a decreased IL-6, IL-12p70 and IL-23 production. In antigen specific T cell stimulation assays, adrenergic β2 receptor activation on bone marrow DCs led to an enhanced potential to induce Foxp3 positive suppressive Treg cells. These effects were independent of IL10-R activation, TGFβ release, or retinoic acid (RA) secretion. Hence, adrenergic receptor β2 activation modulates DC function resulting in skewing towards anti-inflammatory T cell phenotypes

    Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI) expression

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    <p>Abstract</p> <p>Background</p> <p>Mucosal levels of Secretory Leukocyte Protease Inhibitor (SLPI) are specifically reduced in relation to <it>H. pylori</it>-induced gastritis. Progranulin is an epithelial growth factor that is proteolytically degraded into fragments by elastase (the main target of SLPI). Considering the role of SLPI for regulating the activity of elastase, we studied whether the <it>H. pylori</it>-induced reduction of SLPI and the resulting increase of elastase-derived activity would reduce the Progranulin protein levels both <it>ex vivo </it>and <it>in vitro</it>.</p> <p>Methods</p> <p>The expression of Progranulin was studied in biopsies of <it>H. pylori</it>-positive, -negative and -eradicated subjects as well as in the gastric tumor cell line AGS by ELISA, immunohistochemistry and real-time RT-PCR.</p> <p>Results</p> <p><it>H. pylori</it>-infected subjects had about 2-fold increased antral Progranulin expression compared to <it>H. pylori</it>-negative and -eradicated subjects (P < 0.05). Overall, no correlations between mucosal Progranulin and SLPI levels were identified. Immunohistochemical analysis confirmed the upregulation of Progranulin in relation to <it>H. pylori </it>infection; both epithelial and infiltrating immune cells contributed to the higher Progranulin expression levels. The <it>H. pylori</it>-induced upregulation of Progranulin was verified in AGS cells infected by <it>H. pylori</it>. The down-regulation of endogenous SLPI expression in AGS cells by siRNA methodology did not affect the Progranulin expression independent of the infection by <it>H. pylori</it>.</p> <p>Conclusions</p> <p>Taken together, Progranulin was identified as novel molecule that is upregulated in context to <it>H. pylori </it>infection. In contrast to other diseases, SLPI seems not to have a regulatory role for Progranulin in <it>H. pylori</it>-mediated gastritis.</p

    Diabetic gastroparesis: Therapeutic options

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    Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

    The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis

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    <div><p>Objective</p><p>In current clinical practice, optimal treatment of inflammatory bowel disease (IBD) aims at the induction and maintenance of clinical remission. Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to categorize patients with clinical remission into subsets with variable states of immune activation.</p><p>Design</p><p>By using Affymetrix GeneChips, we analysed RNA gene expression profiles of peripheral blood leukocytes from pediatric IBD patients in clinical remission and controls. We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients.</p><p>Results</p><p>Pediatric IBD patients with disease in clinical remission display heterogeneously distributed gene expression profiles that are significantly distinct from controls. We identified three clusters of IBD patients, each displaying specific expression profiles of IBD-associated genes.</p><p>Conclusion</p><p>The expression of immune- and IBD-associated genes in peripheral blood leukocytes from pediatric IBD patients in clinical remission was different from healthy controls, indicating that sub-clinical immune mechanisms are still active during remission. As such, RNA profiling of peripheral blood may allow for non-invasive patient subclassification and new perspectives in treatment regimes of IBD patients in the future.</p></div

    Intranasal Delivery of E-Selectin Reduces Atherosclerosis in ApoE−/− Mice

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    Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or “tolerogenic” responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE−/− mice received intranasal delivery of E-selectin prior to (pre-tolerization) or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE−/− mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke

    Activation of NF-κB driven inflammatory programs in mesenchymal elements attenuates hematopoiesis in low-risk myelodysplastic syndromes

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    Activation of NF-κB signaling in mesenchymal cells is common in LR-MDS.Activation of NF-κB in mesenchymal cells leads to transcriptional overexpression of inflammatory factors including negative regulators of hematopoiesis.Activation of NF-κB attenuates HSPC numbers and function ex vivo

    Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?

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    [EN] Academic spin-offs (ASOs) help universities transfer knowledge or technology through business projects developed by academic staff. This investigation aims at analyzing the critical factors for spin-off creation at universities operating in crisis-raven, entrepreneurship-unfriendly environments. Such factors revolve around four types of resources: environmental, institutional, organizational, and personal. Focusing on a Southern European context, as an example of an unfriendly environment affected by economic crisis, an entrepreneurial university (the Technical University of Valencia in Spain, UPV) is our research setting. Through a case study approach, we examine the potential of UPV as a springboard for ASOs. Our results show an adverse local environment, a rather favorable influence of institutional and organizational drivers, and a mixed role of personal factors. Our findings illustrate that UPV consistently supports spin-off creation due to a greater (rather positive) reflexivity from its institutional, organizational and personal resources than the (negative) imprinting of the unfriendly environment. This helps counter-balance the structural unfriendliness for academic entrepreneurship, and trigger a crisis-led risk-taking attitude by academic staff. Hence, UPV should continue with its current strategy of supporting academic entrepreneurship, and might transfer best practices to other universities also affected by unfavorable environmental conditions. Generally speaking, we would advise universities facing adverse circumstances to develop rules and mechanisms for academic entrepreneurship, carefully revise and improve malfunctions, and become involved throughout the whole process of spin-off development. 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