Steroids in villous atrophy: opening a can of worms?
Ontology highlight
ABSTRACT:
SUBMITTER: Lee L
PROVIDER: S-EPMC5517287 | biostudies-other | 2012 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:IntroductionPersistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD).MethodsWe conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi.ResultsAutoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group ( P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not.DiscussiontTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.
| S-EPMC10749705 | biostudies-literature
Project description:Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis.
| S-EPMC1891516 | biostudies-other
Project description:Parasitic infections are a global occurrence and impact the health of many species. Coinfections, where two or more species of parasite are present in a host, are a common phenomenon across species. Coinfecting parasites can interact directly or indirectly via their manipulation of (and susceptibility to) the immune system of their shared host. Helminths, such as the cestode Schistocephalus solidus, are well known to suppress immunity of their host (threespine stickleback, Gasterosteus aculeatus), potentially facilitating other parasite species. Yet, hosts can evolve a more robust immune response (as seen in some stickleback populations), potentially turning facilitation into inhibition. Using wild-caught stickleback from 20 populations with non-zero S. solidus prevalence, we tested an a priori hypothesis that S. solidus infection facilitates infection by other parasites. Consistent with this hypothesis, individuals with S. solidus infections have 18.6% higher richness of other parasites compared to S. solidus-uninfected individuals from the same lakes. This facilitation-like trend is stronger in lakes where S. solidus is particularly successful but is reversed in lakes with sparse and smaller cestodes (indicative of stronger host immunity). These results suggest that a geographic mosaic of host-parasite co-evolution might lead to a mosaic of between-parasite facilitation/inhibition effects.
| S-EPMC10756930 | biostudies-literature
Project description:BACKGROUND: Small intestinal biopsy with villous atrophy (VA) is the gold standard for the diagnosis of celiac disease (CD). We validated VA (Marsh 3) and small intestinal inflammation without VA (Marsh 1+2) in Swedish regional biopsy registers. METHODS: All pathology departments in Sweden (n = 28) were searched to identify individuals with VA or duodenal/jejunal inflammation. The validation consisted of blinded examination of biopsy samples, manual review of biopsy reports, web surveys, and patient chart reviews of 121 individuals with VA and 39 with inflammation. RESULTS: We identified 29,148 individuals with VA and 13,446 individuals with inflammation. In a blinded examination, Swedish pathologists correctly classified 90% of biopsies with VA. Manual screening of 1,534 biopsy reports (performed by co-author JFL and a research assistant) found that comorbidity other than CD was rare. IBD was the most common comorbidity and occurred in 0.3% of biopsies with VA (1.6% in inflammation). Among 114 patients with VA and available data, 108 (95%) had a clinical diagnosis of CD. 79% of the validated individuals with VA and 64% of those with inflammation had documented gastrointestinal symptoms prior to biopsy. 88% of the validated individuals with VA had positive CD serology before their first biopsy. 172/180 (96%) of Swedish gastroenterologists and 68/68 (100%) of pediatricians perform a small intestinal biopsy in at least 9 out of 10 individuals prior to diagnosis of CD. CONCLUSION: Regional biopsy data are feasible to identify individuals with CD and small-intestinal inflammation. The specificity of CD is high in villous atrophy.
| S-EPMC2664822 | biostudies-other
Project description:BackgroundWe studied the expression of sulphated glycosaminoglycans (GAGs) in coeliac disease (CD) mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy.MethodsWe stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG), short-chain HSPG (?-HSPG) and the proteoglycan syndecan-1 (CD138), which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls.ResultsIn CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1(+) plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6(+) mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19.ConclusionsMatrix expansion, through syndecan-1(+) cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1(+) cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders, IL-6 is upregulated and represents a logical target for immunotherapy in patients with coeliac disease refractory to gluten-free diet.
| S-EPMC4157760 | biostudies-literature
Project description:To examine the association between the previous use of nonolmesartan angiotensin receptor blockers (ARBs) or any angiotensin-converting enzyme inhibitor (ACEI) and subsequent villous atrophy (VA) in patients with small-intestinal VA as compared with general population-matched controls.A case-control study was used to link nationwide histopathology data on 2933 individuals with VA (Marsh grade 3) to the Swedish Prescribed Drug Register to examine the association between the use of ACEIs as well as the specific use of ARBs other than olmesartan and subsequent VA. Olmesartan is not available in Sweden, so this exposure was not examined. All individuals with VA had biopsies performed between July 1, 2005, and January 29, 2008, and matched on age, sex, calendar period of birth, and county of residence to 14,571 controls from the general population.Use of nonolmesartan ARBs was not associated with VA (odds ratio, 0.84; 95% CI, 0.64-1.09; P=.19). Neither was VA associated with a previous medication of any ACEI (odds ratio, 1.08; 95% CI, 0.90-1.30; P=.41). Restricting the analysis to individuals with repeated prescriptions for ACEIs or ARBs revealed only marginally changed risk estimates for VA.The lack of association between the use of ACEIs and nonolmesartan ARBs and subsequent VA suggests that these medications are not a major risk factor for the development of VA in the general population.
| S-EPMC4469984 | biostudies-literature
Project description:In the past decade there have been an increasing number of studies on co-infections between worms and malaria. However, this increased interest has yielded results that have been at times conflicting and made it difficult to clearly grasp the outcome of this interaction. Despite the heterogeneity of study designs, reviewing the growing body of research may be synthesized into some broad trends: Ascaris emerges mostly as protective from malaria and its severe manifestations, whereas hookworm seems to increase malaria incidence. As efforts are made to de-worm populations in malaria endemic areas, there is still no clear picture of the impact these programmes have in terms of quantitative and qualitative changes in malaria.
| S-EPMC3192711 | biostudies-literature
Project description:Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1 (TRPV1) and TRP Ankyrin 1 (TRPA1), are expressed on primary sensory neurons. These thermosensor channels play a role in pain processing. We have provided evidence previously that lipid raft disruption influenced the TRP channel activation, and a carboxamido-steroid compound (C1) inhibited TRPV1 activation. Therefore, our aim was to investigate whether this compound exerts its effect through lipid raft disruption and the steroid backbone (C3) or whether altered position of the carboxamido group (C2) influences the inhibitory action by measuring Ca2+ transients on isolated neurons and calcium-uptake on receptor-expressing CHO cells. Membrane cholesterol content was measured by filipin staining and membrane polarization by fluorescence spectroscopy. Both the percentage of responsive cells and the magnitude of the intracellular Ca2+ enhancement evoked by the TRPV1 agonist capsaicin were significantly inhibited after C1 and C2 incubation, but not after C3 administration. C1 was able to reduce other TRP channel activation as well. The compounds induced cholesterol depletion in CHO cells, but only C1 induced changes in membrane polarization. The inhibitory action of the compounds on TRP channel activation develops by lipid raft disruption, and the presence and the position of the carboxamido group is essential.
| S-EPMC6168298 | biostudies-literature
Project description:BackgroundEvidence suggests that health care data sharing may strengthen care coordination, improve quality and safety, and reduce costs. However, to achieve efficient and meaningful adoption of health care data-sharing initiatives, it is necessary to engage all stakeholders, from health care professionals to patients. Although previous work has assessed health care professionals' perceptions of data sharing, perspectives of the general public and particularly of seldom heard groups have yet to be fully assessed.ObjectiveThis study aims to explore the views of the public, particularly their hopes and concerns, around health care data sharing.MethodsAn original, immersive public engagement interactive experience was developed-The Can of Worms installation-in which participants were prompted to reflect about data sharing through listening to individual stories around health care data sharing. A multidisciplinary team with expertise in research, public involvement, and human-centered design developed this concept. The installation took place in three separate events between November 2018 and November 2019. A combination of convenience and snowball sampling was used in this study. Participants were asked to fill self-administered feedback cards and to describe their hopes and fears about the meaningful use of data in health care. The transcripts were compiled verbatim and systematically reviewed by four independent reviewers using the thematic analysis method to identify emerging themes.ResultsOur approach exemplifies the potential of using interdisciplinary expertise in research, public involvement, and human-centered design to tell stories, collect perspectives, and spark conversations around complex topics in participatory digital medicine. A total of 352 qualitative feedback cards were collected, each reflecting participants' hopes and fears for health care data sharing. Thematic analyses identified six themes under hopes: enablement of personal access and ownership, increased interoperability and collaboration, generation of evidence for better and safer care, improved timeliness and efficiency, delivery of more personalized care, and equality. The five main fears identified included inadequate security and exploitation, data inaccuracy, distrust, discrimination and inequality, and less patient-centered care.ConclusionsThis study sheds new light on the main hopes and fears of the public regarding health care data sharing. Importantly, our results highlight novel concerns from the public, particularly in terms of the impact on health disparities, both at international and local levels, and on delivering patient-centered care. Incorporating the knowledge generated and focusing on co-designing solutions to tackle these concerns is critical to engage the public as active contributors and to fully leverage the potential of health care data use.
| S-EPMC7939935 | biostudies-literature
