-
Clinical Nutrition ESPEN Dec 2023The presented review is an updating of Iron metabolism in context of normal physiology and pathological phases. Iron is one of the vital elements in humans and... (Review)
Review
PURPOSE (BACKGROUND)
The presented review is an updating of Iron metabolism in context of normal physiology and pathological phases. Iron is one of the vital elements in humans and associated into proteins as a component of heme (e.g. hemoglobin, myoglobin, cytochromes proteins, myeloperoxidase, nitric oxide synthetases), iron sulfur clusters (e.g. respiratory complexes I-III, coenzyme Q10, mitochondrial aconitase, DNA primase), or other functional groups (e.g. hypoxia inducible factor prolyl hydroxylases). All these entire iron-containing proteins ar e needed for vital cellular and organismal functions together with oxygen transport, mitochondrial respiration, intermediary and xenobiotic metabolism, nucleic acid replication and repair, host defense, and cell signaling.
METHODS (METABOLIC STRATEGIES)
Cells have developed metabolic strategies to import and employ iron safely. Regulatory process of iron uptake, storage, intracellular trafficking and utilization is vital for the maintenance of cellular iron homeostasis. Cellular iron utilization and intracellular iron trafficking pathways are not well established and very little knowledge about this. The predominant organs, which are associated in the metabolism of iron, are intestine, liver, bone marrow and spleen. Iron is conserved, recycled and stored. The reduced bioavailability of iron in humans has developed extremely efficient mechanisms for iron conservation. Prominently, the losses of iron cannot considerably enhance through physiologic mechanisms, even if iron intake and stores become excessive. Loss of iron is balanced or maintained from dietary sources.
RESULTS (OUTCOMES)
Numerous physiological abnormalities are associated with impaired iron metabolism. These abnormalities are appeared in the form of several diseases. There are duodenal ulcer, inflammatory bowel disease, sideroblastic anaemia, congenital dyserythropoietic anemias and low-grade myelodysplastic syndromes. Hereditary hemochromatosis and anaemia are two chronic diseases, which are responsible for disturbing the iron metabolism in various tissues, including the spleen and the intestine. Impairment in hepatic hepcidin synthesis is responsible for chronic liver disease, which is grounding from alcoholism or viral hepatitis. This condition directs to iron overload that can cause further hepatic damage. Iron has important role in several infectious diseases are tuberculosis, malaria trypanosomatid diseases and acquired immunodeficiency syndrome (AIDS). Iron is also associated with Systemic lupus erythematosus [SLE], cancer, Alzheimer's disease (AD) and post-traumatic epilepsy.
CONCLUSION
Recently, numerous research studies are gradually more dedicated in the field of iron metabolism, but a number of burning questions are still waiting for answer. Cellular iron utilization and intracellular iron trafficking pathways are not well established and very little knowledge about this. Increased information of the physiology of iron homeostasis will support considerate of the pathology of iron disorders and also make available the support to advance treatment.
Topics: Humans; Iron; Hemochromatosis; Iron Overload; Homeostasis; Liver Diseases
PubMed: 38057018
DOI: 10.1016/j.clnesp.2023.10.006 -
The Lancet. Gastroenterology &... Nov 2023Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA...
Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study.
BACKGROUND
Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease.
METHODS
In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data.
FINDINGS
We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet.
INTERPRETATION
Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA.
FUNDING
None.
Topics: Adolescent; Adult; Female; Humans; Male; Atrophy; Autoantibodies; Celiac Disease; IgA Deficiency; Immunoglobulin A; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Transglutaminases
PubMed: 37696284
DOI: 10.1016/S2468-1253(23)00205-4 -
Allergy, Asthma, and Clinical... Dec 2023Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the...
BACKGROUND
Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.
CASE PRESENTATION
A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.
CONCLUSIONS
Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.
PubMed: 38053199
DOI: 10.1186/s13223-023-00859-3 -
Journal of Periodontology Apr 2024The bidirectional link of periodontitis (PD) and gastrointestinal tract (GIT) disorders has been investigated in previous epidemiological studies; however, the...
BACKGROUND
The bidirectional link of periodontitis (PD) and gastrointestinal tract (GIT) disorders has been investigated in previous epidemiological studies; however, the conclusions still remain controversial. The aim of this study was to comprehensively explore the bidirectional causal effect between PD and various GIT diseases.
METHODS
Based on summary-level data of genome-wide association studies (GWASs), a two-sample bidirectional Mendelian randomization (MR) study was undertaken. Single-nucleotide polymorphisms (SNPs) associated with PD or GIT disorders (chronic gastritis [CG], gastric ulcer [GU], duodenal ulcer [DU], gastroesophageal reflux disease [GERD], irritable bowel syndrome [IBS], and diverticular disease of the intestine [DI]) in GWASs were applied as exposure. The primary method employed was the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed to investigate potential pleiotropy.
RESULTS
With regard to the investigation of the causality between PD and GIT disorders, the IVW method revealed that there is a causal impact of PD on GU (odds ratio [OR] 1.088; 95% confidence interval [CI], 1.036-1.141; adjusted p = 0.004) and DI (OR 0.938; 95% CI, 0.911-0.965; adjusted p = 0.000). However, no significant genetic liability was observed for the causal effect of PD on CG, DU, GERD, and IBS. Furthermore, the primary analysis did not demonstrate a causal effect of GIT disorders on PD.
CONCLUSION
This MR study suggests that PD may be associated with an increased risk of GU and a reduced risk of DI, with possibly limited clinical relevance. Further studies are needed to support the conclusions of this MR study.
PubMed: 38563552
DOI: 10.1002/JPER.23-0560 -
Infection Apr 2024This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements.
METHODS
Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically.
RESULTS
H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended.
CONCLUSION
This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.
Topics: Humans; Virulence; Helicobacter pylori; Peptic Ulcer; Stomach Neoplasms; Virulence Factors; Bacterial Proteins; Antigens, Bacterial
PubMed: 38270780
DOI: 10.1007/s15010-023-02159-9 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Areas of the body accessible to gastric secretions, such as the stomach and duodenum, are most commonly damaged by circumscribed lesions of the upper gastrointestinal... (Review)
Review
Areas of the body accessible to gastric secretions, such as the stomach and duodenum, are most commonly damaged by circumscribed lesions of the upper gastrointestinal tract mucosa. Peptic ulcer disease is the term for this illness (PUD). About 80% of peptic ulcers are duodenal ulcers, with stomach ulcers accounting for the remaining 20%. Duodenal ulcers are linked to the two primary results about Helicobacter pylori infection and COX inhibitor users. Additional causes might include drinking, smoking, stress, and coffee consumption. The indications and symptoms of a duodenal ulcer depend on the patient's age and the lesion's location. For duodenal ulcers, proton pump inhibitors (PPIs) are the usual course of treatment. This comprehensive study included an in-depth literature search in the literature and methods section using electronic databases such as PubMed, ScienceDirect, and Google Scholar. The search method included publications published from the inception of the relevant database to the present. Inclusion criteria included studies investigating different treatment options for duodenal ulcer disease, including traditional pharmacotherapy and naturopathic treatments. Data mining includes information on treatment techniques, treatment outcomes, and possible synergies between conventional and herbal treatments. In addition, this review critically examines the available information on the effectiveness, safety, and possible side effects of different treatments. The inclusion of conventional and herbal treatments is intended to provide a comprehensive overview of the many treatment options available for duodenal ulcer disease. A more comprehensive and personalized treatment plan can be achieved by incorporating dietary changes, lifestyle modifications, and, if necessary, herbal therapies to complement other treatments normally.
PubMed: 38837070
DOI: 10.1007/s00210-024-03178-5 -
Gastrointestinal Endoscopy Jul 2023Over-the-scope clips (OTSCs) substantially improved the endoscopic armamentarium for the treatment of severe GI bleeding and can potentially overcome limitations of...
BACKGROUND AND AIMS
Over-the-scope clips (OTSCs) substantially improved the endoscopic armamentarium for the treatment of severe GI bleeding and can potentially overcome limitations of standard clips. Data indicate a superiority of OTSCs in hemostasis as first- and second-line therapy. However, the impact of the OTSC designs, in particular the traumatic (-t) or atraumatic (-a) type, in duodenal ulcer bleeding has not been analyzed so far.
METHODS
This was a retrospective analysis of a prospective collected database from 2009 to 2020 of 6 German endoscopic centers. All patients who underwent emergency endoscopy and were treated using an OTSC for duodenal ulcer bleeding were included. OTSC-t and OTSC-a patients were compared by the Fisher exact test, χ test, or Mann-Whitney U test as appropriate. A propensity score-based 1:1 matching was performed to obtain equal distribution of baseline characteristics in both groups.
RESULTS
The entire cohort comprised 173 patients (93 OTSC-a, 80 OTSC-t). Age, gender, anticoagulant therapy, Rockall score, and treatment regimen had similar distributions in the 2 groups. However, the OTSC-t group showed significantly more active bleeding ulcers (Forrest Ia/b). Matching identified 132 patients (66 in both groups) with comparable baseline characteristics. Initial bleeding hemostasis (OTSC-a, 90.9%; OTSC-t, 87.9%; P = .82) and 72-hour mortality (OTSC-a, 4.5%; OTSC-t, 6.0%; P > .99) were not significantly different, but the OTSC-t group revealed a clearly higher rate of recurrent bleeding (34.9% vs 7.6%, P < .001) and necessity of red blood cell transfusions (5.1 ± 3.4 vs 2.5 ± 2.4 concentrates, P < .001).
CONCLUSIONS
For OTSC use, the OTSC-a should be the preferred option for duodenal ulcer bleeding.
Topics: Humans; Hemostasis, Endoscopic; Duodenal Ulcer; Retrospective Studies; Prospective Studies; Propensity Score; Peptic Ulcer Hemorrhage; Endoscopy, Gastrointestinal; Treatment Outcome
PubMed: 36738794
DOI: 10.1016/j.gie.2023.01.051 -
Cureus Oct 2023Neutrophil-lymphocyte ratio (NLR), a simple, inexpensive, and effective biomarker associated with various inflammatory and neoplastic diseases, has become the focus of...
Assessment of the Relationship Between Neutrophil-Lymphocyte Ratio and Dyspeptic Symptoms in Patients With Peptic Ulcer Diagnosed by Endoscopy and Patients Without Peptic Ulcer.
INTRODUCTION
Neutrophil-lymphocyte ratio (NLR), a simple, inexpensive, and effective biomarker associated with various inflammatory and neoplastic diseases, has become the focus of attention in recent years. Nevertheless, it has not been adequately studied in dyspeptic patients with peptic ulcer (PU) and without PU, i.e., patients with non-ulcer dyspepsia (NUD).
MATERIALS AND METHODS
The population of this retrospective study consisted of patients with dyspeptic complaints who underwent esophagogastroduodenoscopy between April 2023 and June 2023. A total of 180 patients included in the study sample were categorized into two groups based on the endoscopy results: patients without PU or NUD patients (Group 1) and those with PU (Group 2). Age, gender and pre-procedural NLR data, upper gastrointestinal endoscopy results, and the presence of (Hp) in endoscopic biopsy information were recorded for all patients.
RESULTS
Of the 180 patients, 140 were diagnosed with NUD (Group 1), and 40 were diagnosed with PU (Group 2). There was a significant difference between Groups 1 and 2 in terms of NLR (Group 1: 2.5±1.8 vs. Group 2: 3.6±3.7, p=0.014). There was also a significant difference in NLR between Group 1 and Group Gastric Ulcer (p=0.030) but not between Group 1 and Group Duodenal Ulcer (p=0.064). Rates of patients with positive Hp test results were 25% and 32.5% in Groups 1 and 2, respectively, indicating a significant difference between the groups (p=0.026).
CONCLUSION
The NLR measured in patients who presented with dyspeptic complaints was found to be significantly higher in PU patients than in NUD patients. The elevated NLR levels were even more evident in PU patients with GU compared to PU patients with DU.
PubMed: 37954706
DOI: 10.7759/cureus.46820 -
Frontiers in Medicine 2023Contradictory evidence suggested gastric xanthelasma (GX) was associated with some upper gastrointestinal (GI) diseases. Additionally, no research has been performed on...
BACKGROUND
Contradictory evidence suggested gastric xanthelasma (GX) was associated with some upper gastrointestinal (GI) diseases. Additionally, no research has been performed on the relationship between esophageal/duodenal xanthelasma and upper GI diseases.
METHODS
Individuals who underwent esophagogastroduodenoscopy at Tongji Hospital, Tongji Medical College, participated in this retrospective study. This study evaluated whether the risk of GX or esophageal/duodenal xanthelasma was influenced by the following gastroesophageal diseases: superficial gastritis, gastric polyp, bile reflux, peptic ulcer, reflux esophagitis, Barrett's esophagus, esophageal cancer, atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia, gastric cancer, and () infection. Furthermore, subgroup analysis was conducted to establish the relationship between the number of GX and upper GI diseases.
RESULTS
Of the 69,071 subjects reviewed, 1,220 (1.77%) had GX, and 54 (0.08%) had esophageal/duodenal xanthelasma. There was no difference in the prevalence of upper GI diseases between patients with and without esophageal/duodenal xanthelasma. Nevertheless, compared with non-xanthelasma patients, GX patients had a greater proportion of AG, IM, dysplasia, gastric cancer, and infection and a lower incidence of superficial gastritis ( < 0.05). The multivariate logistic regression analysis indicated AG (OR = 1.83, 95%CI: 1.56-2.16), IM (OR = 2.42, 95%CI: 2.41-2.85), and infection (OR = 1.32, 95%CI: 1.17-1.50) were independent risk factors for GX. In addition, patients with multiple GXs had a higher rate of AG and IM than those with single GX.
CONCLUSION
Esophageal/duodenal xanthelasma may not be associated with upper GI diseases, and further research is needed to support this hypothesis. Notably, GX, especially multiple GXs, may be a more easily detected warning sign of AG, IM, or infection.
PubMed: 37727758
DOI: 10.3389/fmed.2023.1252346 -
Pharmaceuticals (Basel, Switzerland) May 2024(-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Mill., L., and Molina. Pharmacological studies have reported its antinociceptive,...
(-)-Fenchone Prevents Cysteamine-Induced Duodenal Ulcers and Accelerates Healing Promoting Re-Epithelialization of Gastric Ulcers in Rats via Antioxidant and Immunomodulatory Mechanisms.
BACKGROUND
(-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Mill., L., and Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities.
METHODS
The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days.
RESULTS
In the cysteamine-induced duodenal ulcer model, fenchone (37.5-300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced ( < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-β). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced ( < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake.
CONCLUSION
(-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.
PubMed: 38794211
DOI: 10.3390/ph17050641