15,613 research outputs found

    The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease.

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    BACKGROUND: Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. AIM: The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. METHODS: Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. CONCLUSIONS: Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.info:eu-repo/semantics/publishedVersio

    Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation

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    Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence of acute pancreatitis. Pancreatic triglyceride lipase (PNLIP) increased in adipose tissue during pancreatitis and entered adipocytes by multiple mechanisms, hydrolyzing adipose triglyceride and generating excess NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike obese adipocyte-specific ATGL knockouts, had lower visceral adipose tissue lipolysis, milder inflammation, less severe organ failure, and improved survival. PNLIP-knockout mice, unlike ATGL knockouts, were protected from adipocyte-induced pancreatic acinar injury without affecting NEFA signaling or acute pancreatitis induction. Therefore, during pancreatitis, unlike diverticulitis, PNLIP leaking into visceral adipose tissue can cause excessive visceral adipose tissue lipolysis independently of adipocyte-autonomous ATGL, and thereby worsen organ failure

    SAPHO: has the time come for tailored therapy?

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    SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a heterogeneous condition combining osteoarticular and cutaneous manifestations. Conventional treatments are mostly ineffective. We hereby report two patients, the first with an aggressive form of disease and the second with an incomplete response to two different anti-TNF-α agents. Both were successfully treated with tocilizumab and ustekinumab, respectively, over a long period of time. A narrative review of a biological therapy in SAPHO syndrome yielded very little information on the specific use of these agents. We highlight the advantages of personalising therapy and describe emerging promising treatments for this disease.info:eu-repo/semantics/publishedVersio

    Paraovarian tumor of borderline malignancy: a case report

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    A case of a 23-year-old woman with a paraovarian tumor is presented. The patient complained of pelvic pain and abdominal swelling. Cystectomy was the initial surgical treatment, but after the histological diagnosis, a staging surgery was carried out. The clinical aspects and subsequent management of related cases are discussed, and a literature review is made

    General Relativistic Mean Field Theory for Rotating Nuclei

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    We formulate a general relativistic mean field theory for rotating nuclei starting from the special relativistic σω\sigma - \omega model Lagrangian. The tetrad formalism is adopted to generalize the model to the accelerated frame.Comment: 13 pages, REVTeX, no figures, submitted to Phys. Rev. Lett., the word `curved' is replaced by `non-inertial' or `accelerated' in several places to clarify the physical situation interested, some references are added, more detail discussions are given with omitting some redundant sentence

    Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium

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    BACKGROUND: The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts intestinal stem cells functions, thus affecting the epithelial structure. METHODS: Mice were fed with a diet containing 5% of the insoluble fiber cellulose or the same diet enriched with an additional 10% of inulin. Using a combination of histochemistry, host cell transcriptomics, 16S microbiome analysis, germ-free, gnotobiotic, and genetically modified mouse models, we analyzed the impact of inulin intake on the colonic epithelium, intestinal bacteria, and the local immune compartment. RESULTS: We show that the consumption of inulin diet alters the colon epithelium by increasing the proliferation of intestinal stem cells, leading to deeper crypts and longer colons. This effect was dependent on the inulin-altered gut microbiota, as no modulations were observed in animals deprived of microbiota, nor in mice fed cellulose-enriched diets. We also describe the pivotal role of γδ T lymphocytes and IL-22 in this microenvironment, as the inulin diet failed to induce epithelium remodeling in mice lacking this T cell population or cytokine, highlighting their importance in the diet-microbiota-epithelium-immune system crosstalk. CONCLUSION: This study indicates that the intake of inulin affects the activity of intestinal stem cells and drives a homeostatic remodeling of the colon epithelium, an effect that requires the gut microbiota, γδ T cells, and the presence of IL-22. Our study indicates complex cross kingdom and cross cell type interactions involved in the adaptation of the colon epithelium to the luminal environment in steady state. Video Abstract

    Diagnosis and outcome of oesophageal Crohn's disease

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    BACKGROUND AND AIMS: Crohn's disease (CD) can involve any part of the gastrointestinal tract. We aimed to characterize clinical, endoscopic, histologic features and treatment outcomes of CD patients with oesophageal involvement. METHODS: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. RESULTS: A total of 40 patients were reported [22 males, mean (±SD, range) age at oesophageal CD diagnosis: 25 (±13.3, 10-71) years and mean time of follow-up: 67 (±68.1, 3-240) months]. Oesophageal involvement was established at CD diagnosis in 26 patients (65%) and during follow-up in 14. CD was exclusively located in the oesophagus in 2 patients. Thirteen patients (32.2%) were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in 5 patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors (PPIs) were administered in 37 patients (92.5%). Three patients underwent endoscopic dilation for symptomatic strictures and none oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients (82.5%) after a mean time of 7 (±5.6, 1-18) months. Follow-up endoscopy was performed in 29/40 patients and 26/29 (89.7%) achieved mucosal healing. CONCLUSION: In this case series the endoscopic and histologic characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing IBD-related therapy occurring in two thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.info:eu-repo/semantics/publishedVersio
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