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1.
J Gastroenterol ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589597

RESUMEN

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

2.
Hepatol Res ; 54(1): 67-77, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37691006

RESUMEN

AIMS: Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. METHODS: This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. RESULTS: Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). CONCLUSIONS: We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

3.
Sci Rep ; 13(1): 20262, 2023 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-37985889

RESUMEN

Not all patients with ulcerative colitis (UC) respond initially to treatment with biologic agents, and predicting their efficacy prior to treatment is difficult. Vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 (α4ß7) integrin, suppresses immune cell migration by blocking the interaction between α4ß7 integrin and mucosal addressin cell adhesion molecule 1. Reports about histological features that predict vedolizumab efficacy are scarce. So, we examined the association between histological features and vedolizumab efficacy. This was a multicenter, retrospective study of patients with UC treated with vedolizumab. Biopsy specimens taken from the colonic mucosa prior to vedolizumab induction were used, and the areas positively stained for CD4, CD68, and CD45 were calculated. Clinical and histological features were compared between those with and without remission at week 22, and the factors associated with clinical outcomes were identified. We enrolled 42 patients. Patients with a high CD4+ infiltration showed a better response to vedolizumab [odds ratio (OR) = 1.44, P = 0.014]. The concomitant use of corticosteroids and high Mayo scores had a negative association with the vedolizumab response (OR = 0.11, P = 0.008 and OR = 0.50, P = 0.009, respectively). Histological evaluation for CD4+ cell infiltration may be helpful in selecting patients who can benefit from vedolizumab.


Asunto(s)
Colitis Ulcerosa , Humanos , Colitis Ulcerosa/metabolismo , Estudios Retrospectivos , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/farmacología , Integrinas , Resultado del Tratamiento
4.
Circ Rep ; 5(8): 331-337, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37564876

RESUMEN

Background: Endomyocardial biopsy (EMB) is a useful modality in diagnosing the origin of cardiomyopathy and the condition of the impaired myocardium. However, the usefulness of obtaining an EMB from the right and left ventricles (RV and LV, respectively), and its associations with echocardiographic parameters, have not been explored. Methods and Results: Ninety-five consecutive patients with non-ischemic cardiomyopathy excluding myocarditis who underwent EMB between July 2017 and May 2019 were studied. Seventy-nine RV and 93 LV biopsy specimens were pathologically analyzed. The relationships among echocardiographic data before EMB and pathologically measured cardiomyocyte diameter (CMD) and interstitial fibrosis (IF) were evaluated. CMD in both LV and RV specimens correlated with echocardiographic LV morphology, but only CMD in the LV was significantly correlated with cardiac function evaluation, including LV ejection fraction, E' and E/E'. In contrast, there were no significant correlations between IF in either the LV or RV and any echocardiographic parameters measured. Furthermore, CMD of both ventricles was significantly correlated with B-type natriuretic peptide (BNP) concentration at EMB, whereas IF of the LV was barely related and IF of the RV was not significantly correlated with BNP concentrations. Conclusions: Pathologically evaluated CMD of EMB specimens of the LV may be more related to functional parameters for heart failure status and LV geometry on echocardiographic examination, than IF.

5.
Indian J Gastroenterol ; 42(5): 701-707, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37505394

RESUMEN

BACKGROUND/PURPOSE OF THIS STUDY: It has been recommended that individuals with inflammatory bowel disease (IBD) be vaccinated against Coronavirus disease - 19 (COVID-19). Recently, we documented the incidence of side effects (SEs) after COVID-19 immunization among individuals with IBD in Japan. However, the study did not show differences between the types of IBD or the patients' clinical backgrounds. In this survey, we aimed at investigating whether the frequency of SEs differed among patients with IBD. METHODS: A cross-sectional survey was conducted among adult patients with IBD at Kobe University between March 2022 and September 2022. RESULTS: Total 195 patients, including 134 with ulcerative colitis (UC) and 61 with Crohn's disease (CD), completed the questionnaire and were included in the analysis. Of these, 92.3%, 91.3% and 44.1% received the initial, second and third dose of the COVID-19 vaccine, respectively. The frequency of local symptoms following the initial, second and third dose of the vaccine was comparable between patients with UC and CD (69.6% vs. 72.7%, 64.2% vs. 69.1% and 63.5% vs. 73.9%, respectively). Muscle pain after the initial and second doses of the COVID-19 vaccine was more common among patients treated with corticosteroids (58.1% vs. 37.6% and 60.0% vs. 31.8%, p < 0.05). Female sex, younger age and current or former smoking were associated with an increased incidence of fever or chills after the initial dose of the vaccine (p < 0.05). In contrast, corticosteroid use was identified as a factor associated with an increased incidence of muscle pain after the initial dose of vaccine (p < 0.05). CONCLUSION: The use of corticosteroids could increase the risk of muscle pain following COVID-19 vaccination. Additionally, factors such as female sex, younger age and current or former smoking can affect the incidence of fever or chills. This information should encourage patients with IBD to get vaccinated against COVID-19.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Colitis Ulcerosa , Coronavirus , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adulto , Femenino , Humanos , Corticoesteroides , Colitis Ulcerosa/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Estudios Transversales , Enfermedades Inflamatorias del Intestino/complicaciones , Japón/epidemiología , Mialgia/complicaciones , Vacunación/efectos adversos
7.
ACG Case Rep J ; 10(4): e01033, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37091209

RESUMEN

Mycobacterium avium complex (MAC) is an important cause of opportunistic infections in immunosuppressed hosts, such as patients with HIV infection and solid organ transplant recipients. MAC disease usually presents in 4 distinct clinical categories: chronic pulmonary disease, disseminated disease, skin/soft-tissue infection, and superficial lymphadenitis. However, clinical reports on gastrointestinal (GI) MAC disease are rare, especially in patients without HIV infection or a history of organ transplantation. We describe a case of non-HIV-associated GI MAC disease in a patient with long-term mycophenolate mofetil use. In this case, MAC organisms in the GI tract and ascites were observed. Endoscopy revealed a unique colonic image with large, deep epithelial denudations. This suggests that apart from patients with HIV infection or transplant recipients, those treated with immunosuppressants can have disseminated MAC. Therefore, internal physicians need to monitor patients undergoing mycophenolate mofetil immunosuppressant therapy.

9.
J Gastroenterol ; 58(5): 444-457, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36739585

RESUMEN

BACKGROUND: Amino acid transporters play an important role in supplying nutrition to cells and are associated with cell proliferation. L-type amino acid transporter 1 (LAT1) is highly expressed in many types of cancers and promotes tumor growth; however, how LAT1 affects tumor development is not fully understood. METHODS: To investigate the role of LAT1 in intestinal tumorigenesis, mice carrying LAT1 floxed alleles that also expressed Cre recombinase from the promoter of gene encoding Villin were crossed to an ApcMin/+ background (LAT1fl/fl; vil-cre; ApcMin/+), which were subject to analysis; organoids derived from those mice were also analyzed. RESULTS: This study showed that LAT1 was constitutively expressed in normal crypt base cells, and its conditional deletion in the intestinal epithelium resulted in fewer Paneth cells. LAT1 deletion reduced tumor size and number in the small intestine of ApcMin/+ mice. Organoids derived from LAT1-deleted ApcMin/+ intestinal crypts displayed fewer spherical organoids with reduced Wnt/ß-catenin target gene expression, suggesting a low tumor-initiation capacity. Wnt3 expression was decreased in the absence of LAT1 in the intestinal epithelium, suggesting that loss of Paneth cells due to LAT1 deficiency reduced the risk of tumor initiation by decreasing Wnt3 production. CONCLUSIONS: LAT1 affects intestinal tumor development in a cell-extrinsic manner through reduced Wnt3 expression in Paneth cells. Our findings may partly explain how nutrient availability can affect the risk of tumor development in the intestines.


Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon , Sistema de Transporte de Aminoácidos y+L , Neoplasias Intestinales , Células de Paneth , Animales , Ratones , Transformación Celular Neoplásica/genética , Mucosa Intestinal/patología , Neoplasias Intestinales/metabolismo , Intestino Delgado/patología , Intestinos , Células de Paneth/metabolismo , Células de Paneth/patología , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Sistema de Transporte de Aminoácidos y+L/metabolismo
11.
Dig Dis Sci ; 68(2): 564-570, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36178566

RESUMEN

BACKGROUND: Patients with inflammatory bowel disease (IBD) are recommended to receive the coronavirus disease 2019 (COVID-19) vaccine. However, a recent survey showed that patients with IBD are more hesitant to receive the vaccine than the general population. Detailed information on the side effects of the COVID-19 vaccine is necessary to encourage vaccination among patients with IBD. AIM: To investigate the frequency of side effects following COVID-19 vaccination in patients with IBD in Japan. STUDY DESIGN: a cross-sectional survey was conducted using a questionnaire administered to adult patients with IBD in a tertiary medical facility. RESULTS: Among the participants who answered the questionnaire, 92.6%, 91.5%, and 41.5% of the participants had received their first, second, and third doses of the COVID-19 vaccine, respectively. Of the vaccinated participants, 88.3%, 86.3%, and 89.0% experienced side effects after receiving the first, second, and third doses of the vaccine, respectively. The incidences of fever, chills, and headaches were significantly higher among female participants than among male participants (p < 0.05). However, the frequencies of most side effects were comparable between the BNT162b2 mRNA and mRNA-1273 vaccines. CONCLUSION: The findings of our survey can help encourage patients with IBD to receive the COVID-19 vaccine.


Asunto(s)
COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades Inflamatorias del Intestino , Adulto , Humanos , Femenino , Masculino , Vacunas contra la COVID-19 , Vacuna BNT162 , Estudios Transversales , Japón , Vacunación
12.
Digestion ; 103(6): 462-469, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36380621

RESUMEN

INTRODUCTION: Sodium picosulfate plus magnesium citrate is a bowel preparation agent with high patient acceptability. However, it is unclear which patients are more likely to have inadequate bowel preparation when using this agent. This study aimed to identify the risk factors for inadequate bowel preparation when using sodium picosulfate plus magnesium citrate for colonoscopy and to develop a scoring model to predict which patients will have inadequate bowel preparation. METHODS: A total of 350 Japanese patients were enrolled from June 2021 to April 2022. Data on patient background, details of colonoscopy, and satisfaction assessment questionnaire results were prospectively collected. The scoring model for inadequate bowel preparation was developed based on multiple logistic regression analyses, and its performance was internally validated using bootstrapping. RESULTS: Adequate bowel preparation was obtained in 295 patients (84.3%); 335 (95.7%) were able to ingest the drug without difficulty. The scoring model consisted of five independent risk factors and points of risk scores were assigned to each one as follows: American Society of Anesthesiologists physical status III (1 point), diabetes comorbidities (5 points), use of laxatives (4 points), no defecation once in a day (2 points), and drug use for mental disorder (6 points). The C-statistics of the scoring system for inadequate bowel preparation was 0.75. DISCUSSION: We identified five risk factors for inadequate bowel preparation when using sodium picosulfate plus magnesium citrate regimen and developed a scoring model for inadequate bowel preparation with satisfactory discrimination and calibration.


Asunto(s)
Catárticos , Compuestos Organometálicos , Humanos , Catárticos/efectos adversos , Polietilenglicoles/efectos adversos , Ácido Cítrico/efectos adversos , Compuestos Organometálicos/efectos adversos , Colonoscopía/métodos
13.
Heart Vessels ; 37(12): 2119-2127, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35701559

RESUMEN

Microbubble testing using transcranial Doppler (TCD) is an important screening tool for diagnosing paradoxical cerebral embolism with high-risk PFO. However, little is known about the association between the microbubble test by TCD and the features of high-risk PFO evaluated by transesophageal echocardiography (TEE). We studied 101 consecutive patients at Showa University, from April 2019 to October 2020, who underwent both TCD and TEE with a sufficient Valsalva maneuver and who were strongly suspected by neurologists as cryptogenic stroke. According to the appearance of microbubbles as high-intensity transient signals (HITS), the TCD grade was stratified into three categories based on the criteria (A: none, no HITS, B: small; 1-10 HITS, and C: large; > 10 HITS, or an uncountable number of HITS). Among patients with RLS through the PFO in TEE, high-risk morphological features of PFO for cerebral embolism were evaluated as follows: (1) tunnel height, (2) tunnel length, (3) total excursion distance of the atrial septum into the right and left atrium, (4) existence of Eustachian valve or Chiari network, (5) angle of PFO from the inferior vena cava, and (6) large shunt (20 or more microbubbles). Of 101 patients (TCD grade; Group A = 49, Group B = 26, Group C = 26), RLS through PFO was detected in 37 patients (grade A = 8, grade B = 6, grade C = 23) by TEE. Among PFO-positive patients, tunnel height, length, total excursion distance into the right and left atria, angle of PFO from the inferior vena cava, and frequency of large shunt in TEE were significantly larger in grade C than in grade A and B (p < 0.05). Additionally, grade C patients had significantly more forms of high-risk PFOs than those in grades A and B when the six features of high-risk PFO were compared. A multivariate logistic regression demonstrated that the tunnel length of PFO and the presence of large shunt in TEE were independently associated with large HITS in TCD (odds ratio: 1.18 and 49.5, 95% confidence interval 1.043-1.337 and 10.05-244.3, p = 0.0086 and p < 0.0001, respectively). In conclusion, the existence of a large HITS detected by TCD may have a screening advantage in predicting the high-risk morphologies of PFO that can cause paradoxical cerebral embolism.


Asunto(s)
Foramen Oval Permeable , Embolia Intracraneal , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/diagnóstico por imagen , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/etiología , Ultrasonografía Doppler Transcraneal/efectos adversos , Ecocardiografía Transesofágica , Accidente Cerebrovascular/etiología
14.
BMC Gastroenterol ; 22(1): 149, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35346067

RESUMEN

BACKGROUND: Behçet's disease (BD) is a recurrent multisystem inflammatory disease. Anti-tumor necrosis factor (TNF) α agents have been used to treat patients with intestinal BD with severe disease activity or those who are resistant to conventional treatments; however, the long-term efficacy of anti-TNFα agents in intestinal BD remains unclear. In the present study, we investigated the clinical outcomes and predictors of discontinuation of anti-TNFα agents in patients with intestinal BD. METHODS: We reviewed the medical records of patients with intestinal BD who received first-line anti-TNFα agents between January 2009 and June 2020. The primary outcome was the percentage of patients who continued anti-TNFα therapy for 48 weeks. Secondary outcomes included the percentage of patients who achieved marked improvement, complete remission, and mucosal healing, as well as predictors of discontinuation of anti-TNFα agents. RESULTS: A total of 29 patients were included in the study. Twenty-two (75.9%) patients continued anti-TNFα therapy for 48 weeks. The percentage of patients who achieved marked improvement, complete remission, and mucosal healing at week 48 was 48.3%, 37.9%, and 48.3%, respectively. At week 96, 11 (37.9%) patients achieved marked improvement, complete remission, and mucosal healing. A higher C-reactive protein level (CRP; ≥ 1 mg/dL) at baseline was a predictor of discontinuation of anti-TNFα agents. CONCLUSIONS: The 48-week continuation rate of anti-TNFα agents was 75.9% in bio-naïve patients with intestinal BD. However, a higher baseline CRP level (≥ 1 mg/dL) was associated with discontinuation of anti-TNFα agents.


Asunto(s)
Síndrome de Behçet , Enfermedades Intestinales , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Síndrome de Behçet/patología , Humanos , Enfermedades Intestinales/tratamiento farmacológico , Intestinos/patología , Inducción de Remisión , Factor de Necrosis Tumoral alfa
15.
Commun Biol ; 5(1): 206, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35246619

RESUMEN

T-cell-specific Rap1 deletion causes spontaneous colitis in mice. In the present study, we revealed that Rap1 deficiency in T cells impaired the preceding induction of intestinal RORγt+ Treg cells. In the large intestinal lamina propria (LILP) of T-cell-specific Rap1-knockout mice (Rap1KO mice), Th17 cells were found to increase in a microbiota-dependent manner, and the inhibition of IL-17A production prevented the development of colitis. In the LILP of Rap1KO mice, RORγt+ Treg cells were scarcely induced by 4 weeks of age. The expression of CTLA-4 on Rap1-deficient Treg cells was reduced and the expression of CD80 and CD86 on dendritic cells was consequently elevated in Rap1KO mice. When cultured under each polarizing condition, Rap1-deficient naïve CD4+ T cells did not show biased differentiation into Th17 cells; their differentiation into Treg cells as well as Th1 and Th2 cells was lesser than that of wild-type cells. Rap1-deficient naïve CD4+ T cells were found to exhibit the defective nuclear translocation of NFAT and formation of actin foci in response to TCR engagement. These data suggest that Rap1 amplifies the TCR signaling required for Treg-mediated control of intestinal colitogenic Th17 responses.


Asunto(s)
Colitis , Células Th17 , Proteínas de Unión al GTP rap1 , Animales , Diferenciación Celular , Colitis/metabolismo , Colitis/prevención & control , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Proteínas de Unión al GTP rap1/genética
16.
Heart Vessels ; 37(5): 755-764, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34677658

RESUMEN

Tricuspid regurgitation (TR) is a common condition that is independently associated with high mortality rates in patients with heart failure (HF). Several studies have demonstrated the clinical efficacy of add-on tolvaptan in patients hospitalized for HF. However, the effects of add-on tolvaptan in patients with significant TR are less well understood. Among the patients with moderate-to-severe TR assessed by transthoracic echocardiography during hospitalization for congestive HF, 39 patients who could complete the clinical course after starting add-on tolvaptan were included in the study. Rehospitalization due to HF and cardiac death were defined as adverse cardiac events in this study. We investigated the presence or absence of cardiac events within 2 years following the introduction of tolvaptan and evaluated echocardiographic functional parameters associated with cardiac events. The average patient age was 75 ± 14 years, and 23 patients (59%) experienced adverse cardiac events within 2 years after add-on tolvaptan administration. Serum creatinine (mg/dL) and brain natriuretic peptide (pg/mL) concentrations at discharge were significantly higher in patients with cardiac events than in those without cardiac events {1.48 [1.02-1.58] vs. 1.07 [0.79-1.41], p = 0.03; 526 [414-1044] vs. 185 [104-476], p = 0.01, respectively}. The presence or absence of past hospitalization for HF was also significantly higher in the event-positive group compared to event-free group (78 vs. 44%, p = 0.04). Comparison of echocardiographic parameters revealed that patients with cardiac events had a significantly lower left ventricular ejection fraction (40 ± 16 vs. 49 ± 15%, p = 0.049) and lower right ventricular fractional area change (RVFAC) (35 ± 12 vs. 45 ± 10%, p = 0.008) than those without cardiac events. Multiple logistic regression analysis revealed that RVFAC and past hospitalization for HF were independently associated with cardiac events following the introduction of tolvaptan (odds ratio, 0.934 and 4.992; p = 0.048 and 0.04, respectively). Right ventricular contractility as well as past history of admission for HF, left ventricular ejection fraction, renal function, and brain natriuretic peptide level at discharge may reflect the clinical outcomes after HF hospitalization in patients with significant TR who were treated with tolvaptan.


Asunto(s)
Insuficiencia Cardíaca , Insuficiencia de la Válvula Tricúspide , Anciano , Anciano de 80 o más Años , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización , Humanos , Persona de Mediana Edad , Péptido Natriurético Encefálico , Volumen Sistólico , Tolvaptán/uso terapéutico , Resultado del Tratamiento , Insuficiencia de la Válvula Tricúspide/diagnóstico , Insuficiencia de la Válvula Tricúspide/tratamiento farmacológico , Función Ventricular Izquierda
17.
Intest Res ; 20(1): 144-149, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33476510

RESUMEN

Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.

18.
Kobe J Med Sci ; 66(4): E139-E148, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33994517

RESUMEN

Daikenchuto (TU-100) is herbal medicine which predominantly contains ginger, Japanese pepper, and ginseng. We investigated whether TU-100 can affect the composition of gut flora and intestinal tumor development using ApcMin/+ mice, a murine model of intestinal tumor. Bacterial 16S rRNA sequencing and short-chain fatty acid analysis were performed on faecal samples. Tumor number and size were analysed. Any change in gene expression of the tumor tissues was assessed by real-time PCR. Principal coordinate analysis (PCoA) showed that the faecal microbiota cluster of TU-100-fed mice was different from the microbiota of control mice. However, no significant difference was observed in the concentration of short-chain fatty acids, tumor number, and gene expression levels between the two groups. Our data showed that TU-100 can affect the intestinal environment; however, it does not contribute in tumor progression or inhibition in our setting.


Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Medicina de Hierbas , Mucosa Intestinal/efectos de los fármacos , Neoplasias Intestinales/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Heces , Microbioma Gastrointestinal/genética , Neoplasias Intestinales/patología , Ratones , Microbiota , Panax , ARN Ribosómico 16S , Reacción en Cadena en Tiempo Real de la Polimerasa , Zanthoxylum , Zingiberaceae
19.
JGH Open ; 4(5): 937-944, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33102767

RESUMEN

BACKGROUND AND AIM: Upper gastrointestinal symptoms (UGSs), including reflux and dyspeptic symptoms (postprandial distress syndrome [PDS] and epigastric pain syndrome [EPS]), affect health-related quality of life. However, the influence of sex on the relationship between body mass index (BMI) and UGSs remains controversial. This study investigates the influence of sex on this association in healthy subjects. METHODS AND RESULTS: We utilized the database of a prospective, multicenter, cohort study of 7112 subjects who underwent upper endoscopy for health screening. A multivariable logistic regression analysis was conducted to assess the association between BMI and UGSs stratified by sex, adjusting for clinical features. The influence of sex on the association between the overlapping of UGSs and BMI in symptomatic subjects was also investigated. Reflux symptoms were significantly associated with high BMI (multivariable odds ratio [OR] 1.36; 95% confidence interval [CI] 1.10-1.67, P = 0.004). PDS symptoms were significantly associated with low BMI (OR 2.37; 95% CI 1.70-3.25; P < 0.0001), but EPS symptoms were not associated with BMI. The association between reflux symptoms and higher BMI was limited to men (men: OR 1.40; 95% CI 1.10-1.77; P = 0.005, women: P = 0.40). sex did not influence the association between the presence of PDS symptoms and lower BMI. The percentage of overlapping of all three symptoms (reflux, PDS, and EPS) was higher in women than in men (19.9% [58/292] vs 10.5% [49/468], P = 0.0002). CONCLUSIONS: The influence of BMI on the presence of UGSs was significantly different according to sex in this large-scale cohort.

20.
J Phys Chem B ; 124(33): 7251-7257, 2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32697908

RESUMEN

Salts containing the merocyanine form of a pyridinium-fused spiropyran ([6'-MC]X; X = I and PF6) were prepared, and their crystal structures were determined. In addition, the photochromic properties of the salts were spectroscopically and kinetically investigated. In the solution state, the salts exhibited negative photochromism. Theoretical calculations revealed that the negative photochromism of the salt originates from the drastic stabilization of the merocyanine structure by electron delocalization of the pyridinium ring. Furthermore, the salts containing the merocyanine and spiropyran forms ([6'-MC]I, [6'-MC]PF6, and [6'-SP]PF6) were obtained by recrystallization. The crystals of [6'-SP]PF6 exhibited positive photochromism in the solid state; however, no photochromism was observed in the [6'-MC]X crystals.

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