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1.
Digestion ; : 1, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857583

ABSTRACT

INTRODUCTION: Crohn's disease (CD) induces persistent inflammation throughout the gastrointestinal (GI) tract, potentially resulting in complications such as intestinal stenosis and fistulas, particularly in the small bowel. Small bowel capsule endoscopy (SBCE) is recommended for monitoring CD, especially when GI tract patency is maintained. This study aimed to retrospectively assess patients with CD who underwent SBCE to determine the timing of clinical changes and address the current lack of evidence regarding GI tract patency loss during CD treatment. METHODS: Of the 166 consecutive patients who underwent SBCE at our institution, 120 were followed up and included in this study. Forty-six patients were excluded due to colitis type or immediate treatment changes post-SBCE. This study focused on the primary and secondary endpoints, including the cumulative stricture-free rate of the GI tract, emergency hospitalization post-SBCE, and post-SBCE treatment strategies, at the discretion of the attending physicians. RESULTS: Demographic data revealed that the mean age of the study population was 43 years and that there was a male predominance (75%). The median disease duration was 12 years and the mean Crohn's Disease Activity Index was 98. During a 1,486-day observation period, 37% of patients experienced treatment changes. A Lewis score of >264 and perianal lesions were identified as independent risk factors for additional treatment needs. Emergency hospitalization occurred in 6% of patients and GI patency failure in 11%. Female sex and Lewis score>264 were associated with higher risks. GI patency rate declined 2 years after SBCE. CONCLUSIONS: For patients who experienced no treatment changes based on SBCE results, it is recommended to undergo SBCE monitoring at intervals of no longer than 2 years.

2.
Dig Dis Sci ; 69(7): 2573-2585, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38713271

ABSTRACT

BACKGROUND: Numerous biological interventions and small molecules are used to treat Crohn's disease; however, the effectiveness of these treatments varies largely. Non-responsiveness to biological therapies is associated with interleukin (IL)-18 gene polymorphisms and high IL-18 expression has been implicated in the pathogenesis of Crohn's disease. AIMS: The aim of this study was to elucidate the expression of precursor and mature IL-18 in patients with Crohn's disease who exhibited varied responses to cytokine-targeted treatments and determine whether selective inhibition of mature IL-18 offers a novel therapeutic avenue. METHODS: We generated a monoclonal antibody that specifically recognizes the neoepitope of caspase-cleaved mature IL-18. Expression of precursor and mature IL-18 was analyzed in patients with Crohn's disease. Anti-mature IL-18 monoclonal antibodies were intraperitoneally administered in an acute colitis mouse model, and the disease activity index, body weight loss, tissue pathology, proinflammatory cytokine expression, goblet cell function, and microbiota composition were assessed. RESULTS: Precursor and mature IL-18 expression was upregulated and goblet cell function was impaired in patients with Crohn's disease who were unresponsive to biological therapies. Administration of anti-mature IL-18 antibodies ameliorated induced colitis by repairing goblet cell function and restoring the mucus layer. CONCLUSIONS: The newly developed monoclonal antibody holds promise as a therapeutic alternative for Crohn's disease.


Subject(s)
Antibodies, Monoclonal , Crohn Disease , Goblet Cells , Interleukin-18 , Interleukin-18/metabolism , Interleukin-18/immunology , Animals , Goblet Cells/immunology , Goblet Cells/pathology , Goblet Cells/drug effects , Humans , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Mice , Crohn Disease/immunology , Crohn Disease/drug therapy , Female , Male , Disease Models, Animal , Colitis/immunology , Colitis/drug therapy , Adult , Mice, Inbred C57BL
3.
Sci Rep ; 14(1): 8398, 2024 04 10.
Article in English | MEDLINE | ID: mdl-38600251

ABSTRACT

Allergic rhinitis (AR) is caused by type I hypersensitivity reaction in the nasal tissues. The interaction between CD300f and its ligand ceramide suppresses immunoglobulin E (IgE)-mediated mast cell activation. However, whether CD300f inhibits the development of allergic rhinitis (AR) remains elusive. We aimed to investigate the roles of CD300f in the development of AR and the effectiveness of intranasal administration of ceramide liposomes on AR in murine models. We used ragweed pollen-induced AR models in mice. Notably, CD300f deficiency did not significantly influence the ragweed-specific IgE production, but increased the frequency of mast cell-dependent sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in our models. Similar results were also obtained for MCPT5-exprssing mast cell-specific loss of CD300f. Importantly, intranasal administration of ceramide liposomes reduced the frequency of sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in AR models. Thus, CD300f-ceramide interaction, predominantly in mast cells, alleviates the symptoms and progression of AR. Therefore, intranasal administration of ceramide liposomes may be a promising therapeutic approach against AR by targeting CD300f.


Subject(s)
Liposomes , Rhinitis, Allergic , Animals , Mice , Administration, Intranasal , Sneezing , Ceramides , Disease Models, Animal , Rhinitis, Allergic/drug therapy , Immunoglobulin E , Nasal Mucosa , Mice, Inbred BALB C , Ovalbumin
4.
Rev Esp Enferm Dig ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38525848

ABSTRACT

Since even subtle mucosal changes may be depicted using virtual endoscopy created by the three-dimensional reconstruction of MDCT images, we developed a novel diagnostic imaging system that integrates and displays virtual enteroscopy, curved planar reconstruction, and a virtual unfolded view, the width of which changes with increases/decreases in the inner luminal diameter. The system is also equipped with artificial intelligence that superimposes and displays depressed areas, generates an automatic small bowel centerline that connects fragmented small bowel regions, and performs electronic cleansing. We retrospectively evaluated the diagnostic performance of this system for small bowel lesions in Crohn's disease, which were divided into two groups: endoscopically-observable and endoscopically-unobservable. Lesion detection rates for stenoses, longitudinal ulcers with a cobblestone appearance, and scars were excellent in both groups. This system, when used in combination with endoscopy, shows slight mucosal changes in areas in which an endoscope cannot reach due to strictures, thereby extending the range of observation of the small bowel. This system is a useful diagnostic modality that has the capacity to assess mucosal healing and provide extraluminal information.

6.
Ir J Med Sci ; 193(1): 173-179, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37432526

ABSTRACT

BACKGROUND: Rebleeding after hemostasis of the gastroduodenal ulcer (GDU) is one of the indicators associated with death among GDU patients. However, there are few studies on risk score that contribute to rebleeding after endoscopic hemostasis of bleeding peptic ulcers. AIMS: The aim of this study was to identify factors associated with rebleeding, including patient factors, after endoscopic hemostasis of bleeding gastroduodenal ulcers and to stratify the risk of rebleeding. METHODS: We retrospectively enrolled 587 consecutive patients who were treated for Forrest Ia to IIa bleeding gastroduodenal ulcers with endoscopic hemostasis at three institutions. Risk factors associated with rebleeding were assessed using univariate and multivariate logistic regression analyses. The Rebleeding Nagoya University (Rebleeding-N) scoring system was developed based on the extracted factors. The Rebleeding-N score was internally validated using bootstrap resampling methods. RESULTS: Sixty-four patients (11%) had rebleeding after hemostasis of gastroduodenal ulcers. Multivariate logistic regression analysis revealed four independent rebleeding risk factors: blood transfusion, albumin <2.5, duodenal ulcer, and diameter of the exposed vessel ≧2 mm. Patients with 4 risk factors in the Rebleeding-N score had a 54% rebleeding rate, and patients with 3 risk factors had 44% and 25% rebleeding rates. In the internal validation, the mean area under the curve of the Rebleeding-N score was 0.830 (95% CI = 0.786-0.870). CONCLUSIONS: Rebleeding after clip hemostasis of bleeding gastroduodenal ulcers was associated with blood transfusion, albumin <2.5, diameter of the exposed vessel ≧2 mm, and duodenal ulcer. The Rebleeding-N score was able to stratify the risk of rebleeding.


Subject(s)
Duodenal Ulcer , Peptic Ulcer , Humans , Duodenal Ulcer/therapy , Peptic Ulcer Hemorrhage/therapy , Retrospective Studies , Risk Factors , Recurrence , Albumins
7.
Heart Vessels ; 39(4): 310-318, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38062328

ABSTRACT

BACKGROUND: The increased amount of contrast media in frequency-domain optical coherence tomography (FD-OCT) imaging during percutaneous coronary intervention (PCI) has raised potential concerns regarding impairment of renal function. OBJECTIVES: This study aimed to evaluate the effectiveness of heparinized saline flush in FD-OCT-guided PCI and identify clinical factors contributing to optimal image quality. METHODS: We retrospectively collected 100 lesions from 90 consecutive patients, and a total of 200 pullbacks were analyzed for the initial and final evaluation in which saline was used as the flushing medium. RESULTS: The study population had a mean age of 73, with 52% having chronic kidney disease (CKD). The median amount of contrast used was 28 ml, and no complications were observed associated with saline flush OCT. Imaging quality was then categorized as excellent, good, or unacceptable. Among the total runs, 87% demonstrated clinically acceptable image quality, with 66.5% classified as excellent images and 20.5% classified as good images. Independent predictors of excellent images included lumen area stenosis ≥ 70% (adjusted odds ratio [OR] 2.37, 95% confidence interval [CI] 1.02-5.47, P = 0.044), and the use of intensive flushing (adjusted OR 2.06, 95% CI 1.11-3.86, P = 0.023) defined as a deep engagement of guiding catheter (GC) or a selective insertion of guide extension catheter (GE). Intensive flushing was performed in 60% of the total pullbacks, and it was particularly effective in improving image quality in the left coronary artery (LCA). CONCLUSION: The use of saline flush during FD-OCT imaging was safe and feasible, which had a benefit in renal protection with adequate imaging quality.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Humans , Aged , Tomography, Optical Coherence/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Retrospective Studies , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Treatment Outcome , Coronary Angiography , Predictive Value of Tests
8.
Inflamm Bowel Dis ; 2023 Dec 23.
Article in English | MEDLINE | ID: mdl-38141180

ABSTRACT

BACKGROUND: Antitumor necrosis factor (TNF)-α antibodies have improved the outcome of inflammatory bowel disease (IBD); but half of patients remain unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated with resistance to anti-TNF-α antibodies, but therapies targeting IL-18 have not been clinically applied. Only the mature protein is biologically active, and we aimed to investigate whether specific inhibition of mature IL-18 using a monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 could be an innovative treatment for IBD. METHODS: The expression of precursor and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 mice by administering dextran sulfate sodium (DSS), followed by injection with anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to histological analysis, immunohistochemistry, immunoblotting, and quantitative polymerase chain reaction. Colon epithelial permeability and microbiota composition were analyzed. RESULTS: Mature IL-18 expression was elevated in colon tissues of patients with active ulcerative colitis. Administration of anti-IL-18 neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced interferon-γ, TNF-α, and chemokine (CXC motif) ligand-2 production and epithelial cell permeability; promoted goblet cell function; and altered the intestinal microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with anti-TNF-α Ab suppressed acute and chronic colitis additively by suppressing cytokine expressions and reducing cell permeability by upregulating claudin1 and occludin expression. CONCLUSIONS: Anti-IL-18 neoepitope mAb ameliorates acute and chronic colitis, suggesting that this mAb will be an innovative therapeutic option for IBD.


We investigate a novel monoclonal antibody that specifically recognizes a neoepitope of caspase-cleaved IL-18 and alleviates dextran sulfate sodium-induced colitis by suppressing the secretion of inflammatory cytokines, improving intestinal epithelial permeability, promoting goblet cell function, and regulating intestinal microbiota.

9.
Inflamm Intest Dis ; 8(2): 60-68, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37901340

ABSTRACT

Introduction: Ustekinumab (UST) has been approved for the treatment of moderate-to-severe ulcerative colitis (UC). Real-world data showing the effectiveness and safety of UST are necessary to confirm the results of clinical trials for applicability in daily clinical practice. Although some studies have reported real-world evidence of UST, only few studies have confirmed its effectiveness in the real world. The aim of this study was to assess the short- and long-term effectiveness, durability, safety, and risk factors for discontinuation of UST in UC in clinical practice. Methods: This was a retrospective, single-center, observational study. From March 2020 to January 2023, all consecutive patients with active UC who were treated with UST at Nagoya University Hospital were included. The primary outcome was the clinical remission rate at weeks 2-8 and weeks 24-48. The secondary outcomes included clinical response, persistence of UST therapy, endoscopic changes during follow-up, risk factors for UST discontinuation, and occurrence of any adverse events. The clinical effectiveness was evaluated using the Lichtiger score. Results: A total of 31 patients were included in this study. The clinical remission rates were 9.7%, 29.0%, 54.8%, and 64.5% at weeks 2, 8, 24, and 48, respectively. Twelve (38.7%) patients discontinued UST during the follow-up period. The probability of continuing UST was 93.5%, 80.6%, 77%, and 70% at weeks 2, 8, 24, and 48, respectively. The major reason for discontinuation of UST was primary failure (75.0%). A high baseline C-reactive protein (CRP) level was a significant risk factor for the discontinuation of UST. No adverse events were observed in this study. Conclusion: UST is effective for patients with UC. High CRP levels were identified as a risk factor for UST discontinuation. The findings of this study would help clinicians to select appropriate treatment options for patients with UC by identifying the risk factors for treatment discontinuation.

10.
Transplant Proc ; 55(9): 2046-2052, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37783591

ABSTRACT

This study aimed to analyze male renal transplant recipients' experience with their partners' pregnancy and childbirth and to investigate their methods of nursing their condition. We performed semistructured interviews and collected data from 6 Japanese males who underwent a kidney transplant after their partner had given birth. The data were analyzed using the Qualitative Synthesis Method (KJ Method). The mean age of the participants at data collection was 40.3 ± 4.7 years, whereas it was 34.7 ± 5.8 years when the transplant was performed. The Qualitative Synthesis Method revealed 7 symbols related to the pregnancy and childbirth experience of the partners of male kidney transplant recipients. Males who received a kidney transplant struggled with severe renal disease before the transplant. They also experienced indecisiveness about whether they should go through with the transplant. However, their lives changed because of the transplant and having children. This situation resulted in a sense of responsibility and a reason to live robustly for the male kidney transplant recipients. Nevertheless, they faced distress as kidney transplant patients. Their wives supported them through this experience. They communicated to their children what they learned from the experience while effectively dealing with their condition. The improvement in their sexual function resulting from the transplant influenced their determination to get married. It is necessary to offer information about the recovery of fertility and the possibility of having a child when choosing renal replacement therapy, give explanations based on evidence, and construct a counseling system.


Subject(s)
Kidney Transplantation , Pregnancy , Female , Child , Humans , Male , Adult , Middle Aged , Kidney Transplantation/adverse effects , Kidney Transplantation/psychology , Spouses , Transplant Recipients/psychology , Fertility
11.
JCI Insight ; 8(21)2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37819721

ABSTRACT

The penetration of allergens through the epithelial layer is the initial step in the development of allergic conjunctivitis. Although pollinosis patients manifest symptoms within minutes after pollen exposure, the mechanisms of the rapid transport of the allergens remain unclear. In the present study, we found that the instillation of pollen shells rapidly induces a large number of goblet cell-associated antigen passages (GAPs) in the conjunctiva. Antigen acquisition by stromal cells, including macrophages and CD11b+ dendritic cells, correlated with surface GAP formation. Furthermore, a substantial amount of antigen was transported to the stroma during the first 10 minutes of pollen exposure, which was sufficient for the full induction of an allergic conjunctivitis mouse model. This inducible, rapid GAP formation and antigen acquisition were suppressed by topical lidocaine or trigeminal nerve ablation, indicating that the sensory nervous system plays an essential role. Interestingly, pollen shell-stimulated GAP formation was not suppressed by topical atropine, suggesting that the conjunctival GAPs and intestinal GAPs are differentially regulated. These results identify pollen shell-induced GAP as a therapeutic target for allergic conjunctivitis.


Subject(s)
Conjunctivitis, Allergic , Animals , Mice , Humans , Conjunctivitis, Allergic/diagnosis , Conjunctivitis, Allergic/drug therapy , Goblet Cells , Allergens , Pollen , Conjunctiva
12.
BMC Gastroenterol ; 23(1): 290, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620810

ABSTRACT

BACKGROUND: Obscure gastrointestinal bleeding refers to bleeding for which the source cannot be ascertained even through balloon-assisted endoscopy. In certain instances, Dieulafoy's lesion in the small bowel is presumed to be the underlying cause. AIM: This retrospective study aimed to elucidate the clinical characteristics of Dieulafoy's lesion in the small bowel as diagnosed via double-balloon endoscopy while also exploring the feasibility of predicting bleeding from Dieulafoy's lesion prior to endoscopy in cases of obscure gastrointestinal bleeding. METHODS: A comprehensive analysis of our database was conducted, identifying 38 patients who received a diagnosis of Dieulafoy's lesion and subsequently underwent treatment via double-balloon endoscopy. The clinical background, diagnosis, and treatment details of patients with Dieulafoy's lesion were carefully examined. RESULTS: The median age of the 38 patients was 72 years, and 50% of the patients were male. A total of 26 (68%) patients exhibited a high comorbidity index. The upper jejunum and lower ileum were the most frequently reported locations for the occurrence of Dieulafoy's lesion in the small bowel. The detected Dieulafoy's lesions exhibited active bleeding (n = 33) and an exposed vessel with plaque on the surface (n = 5). Rebleeding after endoscopic treatment occurred in 8 patients (21%, median period: 7 days, range: 1-366 days). We conducted an analysis to determine the definitive nature of the initial double-balloon endoscopy diagnosis. Multivariate analysis revealed that hematochezia of ≥ 2 episodes constituted the independent factor associated with ≥ 2 double-balloon endoscopy diagnoses. Additionally, we explored factors associated with rebleeding following endoscopic treatment. Although the number of hemoclips utilized displayed a likely association, multivariate analysis did not identify any independent factor associated with rebleeding. CONCLUSION: If a patient encounters multiple instances of hematochezia, promptly scheduling balloon-assisted endoscopy, equipped with optional instruments without delay is advised, after standard endoscopic evaluation with esophagogastroduodenoscopy and colonoscopy is unrevealing.


Subject(s)
Endoscopy, Gastrointestinal , Intestine, Small , Humans , Male , Aged , Female , Retrospective Studies , Intestine, Small/diagnostic imaging , Colonoscopy , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy
13.
Front Immunol ; 14: 1173069, 2023.
Article in English | MEDLINE | ID: mdl-37275864

ABSTRACT

Background: Patients with food allergy often suffer from atopic dermatitis, in which Staphylococcus aureus colonization is frequently observed. Staphylococcus aureus δ-toxin activates mast cells and promotes T helper 2 type skin inflammation in the tape-stripped murine skin. However, the physiological effects of δ-toxin present on the steady-state skin remain unknown. We aimed to investigate whether δ-toxin present on the steady-state skin impacts the development of food allergy. Material and methods: The non-tape-stripped skins of wild-type, KitW-sh/W-sh, or ST2-deficient mice were treated with ovalbumin (OVA) with or without δ-toxin before intragastric administration of OVA. The frequency of diarrhea, numbers of jejunum or skin mast cells, and serum levels of OVA-specific IgE were measured. Conventional dendritic cell 2 (cDC2) in skin and lymph nodes (LN) were analyzed. The cytokine levels in the skin tissues or culture supernatants of δ-toxin-stimulated murine keratinocytes were measured. Anti-IL-1α antibody-pretreated mice were analyzed. Results: Stimulation with δ-toxin induced the release of IL-1α, but not IL-33, in murine keratinocytes. Epicutaneous treatment with OVA and δ-toxin induced the local production of IL-1α. This treatment induced the translocation of OVA-loaded cDC2 from skin to draining LN and OVA-specific IgE production, independently of mast cells and ST2. This resulted in OVA-administered food allergic responses. In these models, pretreatment with anti-IL-1α antibody inhibited the cDC2 activation and OVA-specific IgE production, thereby dampening food allergic responses. Conclusion: Even without tape stripping, δ-toxin present on skin enhances epicutaneous sensitization to food allergen in an IL-1α-dependent manner, thereby promoting the development of food allergy.


Subject(s)
Dermatitis, Atopic , Food Hypersensitivity , Mice , Animals , Staphylococcus aureus , Disease Models, Animal , Interleukin-1 Receptor-Like 1 Protein , Immunoglobulin E , Ovalbumin , Exotoxins
14.
STAR Protoc ; 4(2): 102335, 2023 05 25.
Article in English | MEDLINE | ID: mdl-37243601

ABSTRACT

Transcytosis is the primary mechanism by which macro-molecules transverse epithelial cell barriers. Here, we present an assay for measuring transcytosis and recycling of IgG in intestinal epithelial Caco-2 cells and primary human intestinal organoids. We describe steps for establishing human enteroids or Caco-2 cells and plating monolayers. We then provide procedures for a transcytosis and recycling assay and a luciferase assay. The protocol facilitates quantification of membrane trafficking and can be used to probe endosomal compartments unique to polarized epithelia. For complete details on the use and execution of this protocol, please refer to Maeda K et al. (2022).1.

15.
J Atheroscler Thromb ; 30(12): 1778-1790, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37100628

ABSTRACT

AIM: This study aimed to investigate the association between a combination of elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels and target lesion revascularization (TLR) following everolimus-eluting stent (EES) implantation. The adverse impact of clinical, lesion, and procedural characteristics on TLR in patients with elevated TG and reduced HDL-C levels was also assessed. METHODS: We retrospectively collected data on 3,014 lesions from 2,022 consecutive patients, who underwent EES implantation at Koto Memorial Hospital. Atherogenic dyslipidemia (AD) is defined as a combination of non-fasting serum TG ≥ 175 mg/dL and HDL-C <40 mg/dL. RESULTS: AD was observed in 212 lesions in 139 (6.9%) patients. The cumulative incidence of clinically driven TLR was significantly higher in patients with AD than in those without AD (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.43-3.73, P=0.0006). Subgroup analysis showed that AD increased the risk of TLR with the implantation of small stents (≤ 2.75 mm). Multivariable Cox regression analysis showed that AD was an independent predictor of TLR in the small EES stratum (adjusted HR 3.00, 95% CI 1.53-5.93, P=0.004), whereas the incidence of TLR was similar in the non-small-EES stratum, irrespective of the presence or absence of AD. CONCLUSIONS: Patients with AD had a higher risk of TLR after EES implantation, and this risk was greater for lesions treated with small stents.


Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Hypertriglyceridemia , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Everolimus , Sirolimus/therapeutic use , Myocardial Infarction/etiology , Drug-Eluting Stents/adverse effects , Lipoproteins, HDL , Lipoproteins, LDL , Retrospective Studies , Treatment Outcome , Percutaneous Coronary Intervention/adverse effects , Stents/adverse effects , Hypertriglyceridemia/etiology , Hypertriglyceridemia/drug therapy , Risk Factors , Coronary Artery Disease/complications
16.
Nat Commun ; 14(1): 1417, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36932081

ABSTRACT

Gel-forming mucins secreted by conjunctival goblet cells have been implicated in the clearance of allergens, pathogens, and debris. However, their roles remain incompletely understood. Here we show that human and mouse conjunctival goblet cell mucins have Alcian blue-detectable sialic acids, but not sulfates in the steady state. Interestingly, Balb/c mouse strain lacks this sialylation due to a point mutation in a sialyltransferase gene, St6galnac1, which is responsible for sialyl-Tn synthesis. Introduction of intact St6galnac1 to Balb/c restores the sialylation of conjunctival goblet cell mucus. Sialylated mucus efficiently captures and encapsulates the allergen particles in an impenetrable layer, leading to the protection of mice from the development of allergic conjunctivitis. Expression of ST6GALNAC1 and sialyl-Tn is upregulated in humans under conditions with chronic stimuli. These results indicate that the sialylated glycans on the ocular mucins play an essential role in maintaining the conjunctival mucosa by protecting from the incoming foreign bodies such as allergen particles.


Subject(s)
Goblet Cells , Mucins , Mice , Humans , Animals , Goblet Cells/metabolism , Mucins/genetics , Mucins/metabolism , Conjunctiva , Mucus/metabolism , Allergens
17.
Nutrients ; 15(6)2023 Mar 19.
Article in English | MEDLINE | ID: mdl-36986203

ABSTRACT

The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.


Subject(s)
Diet, High-Fat , Tight Junctions , Animals , Mice , Diet, High-Fat/adverse effects , Epithelial Cell Adhesion Molecule/metabolism , Tight Junctions/metabolism , Proteomics , Mice, Inbred C57BL , Intestinal Mucosa/metabolism
18.
Transplant Direct ; 9(3): e1457, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36860659

ABSTRACT

A valid and reliable instrument that can measure adherence is needed to identify nonadherent patients and to improve adherence. However, there is no validated Japanese self-report instrument to evaluate adherence to immunosuppressive medications for transplant patients. The purpose of this study was to determine the reliability and validity of the Japanese version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS). Methods: We translated the BAASIS into Japanese and developed the Japanese version of the BAASIS (J-BAASIS) according to the International Society of Pharmacoeconomics and Outcomes Research task force guidelines. We analyzed the reliability (test-retest reliability and measurement error) and validity of the J-BAASIS (concurrent validity with the medication event monitoring system and the 12-item Medication Adherence Scale) referring to the COSMIN Risk of Bias checklist. Results: A total of 106 kidney transplant recipients were included in this study. In the analysis of test-retest reliability, Cohen's kappa coefficient was found to be 0.62. In the analysis of measurement error, the positive and negative agreement were 0.78 and 0.84, respectively. In the analysis of concurrent validity with the medication event monitoring system, sensitivity and specificity were 0.84 and 0.90, respectively. In the analysis of concurrent validity with the 12-item Medication Adherence Scale, the point-biserial correlation coefficient for the "medication compliance" subscale was 0.38 (P < 0.001). Conclusions: The J-BAASIS was determined to have good reliability and validity. Using the J-BAASIS to evaluate adherence can help clinicians to identify medication nonadherence and institute appropriate corrective measures to improve transplant outcomes.

19.
Aliment Pharmacol Ther ; 57(11): 1249-1257, 2023 06.
Article in English | MEDLINE | ID: mdl-36644995

ABSTRACT

BACKGROUND: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1-kestose is effective for active ulcerative colitis remains controversial. AIMS: This randomised, double-blind, placebo-controlled pilot trial investigated the efficacy of 1-kestose against active ulcerative colitis. METHODS: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1-kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. RESULTS: The clinical activity index at week 8 was significantly lower in the 1-kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1-kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha-diversity in the 1-kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short-chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups. DISCUSSION: Oral 1-kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome.


Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Pilot Projects , Double-Blind Method , Dietary Supplements , Treatment Outcome , Remission Induction
20.
J Gastroenterol Hepatol ; 38(5): 761-767, 2023 May.
Article in English | MEDLINE | ID: mdl-36648892

ABSTRACT

BACKGROUND AND AIM: Double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable procedure for patients with altered gastrointestinal anatomy. Nonetheless, it is time-consuming and burdensome for both patients and endoscopists, partly because route selection in the reconstructed bowel with complicating loop is challenging. Carbon dioxide insufflation enterography is reportedly useful for route selection in the blind loop. This prospective randomized clinical trial investigated the usefulness of carbon dioxide insufflation enterography for route selection by comparing it with conventional observation. METHODS: Patients scheduled to undergo DBERC were consecutively registered. They were divided into carbon dioxide insufflation enterography and conventional groups via randomization according to stratification factors, type of reconstruction methods, and experience with DBERC. The primary endpoint was the correct rate of initial route selection. The secondary endpoints were the insertion time, examination time, amount of anesthesia drugs, and complications. RESULTS: The correct rate of route selection was significantly higher in the carbon dioxide insufflation enterography group (23/25, 92%) than in the visual method (15/25, 60%) (P = 0.018). The insertion time was significantly shorter in the carbon dioxide insufflation enterography group than in the visual group (10.8 ± 11.1 min vs 29.8 ± 15.7 min; P < 0.001). No significant differences in complications were noted between the two groups. The amounts of sedatives and analgesics used were significantly lower in the carbon dioxide insufflation enterography group (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: Carbon dioxide insufflation enterography can reduce the burden of DBERC on patients and endoscopists by shortening the examination time and reducing the amount of medication.


Subject(s)
Carbon Dioxide , Insufflation , Humans , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Prospective Studies , Endoscopy, Gastrointestinal/methods , Cholangiography , Insufflation/methods
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