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2.
Clin Gastroenterol Hepatol ; 21(3): 741-749.e3, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35952942

RESUMO

BACKGROUND & AIMS: Although perceived stress (PS) has been associated with symptomatic flares in inflammatory bowel disease, clinical and physiological measures associated with perceived stress and flare are not known. The aim of this study was to identify physiological factors associated with perceived stress in ulcerative colitis (UC) subjects, and their relationship with flare. METHODS: Patients with UC in clinical remission (Simple Colitis Clinical Activity Index [SCCAI] score <5) underwent clinical and behavioral assessments, morning salivary cortisol measurements, autonomic nervous system activity testing (heart rate variability, electrodermal activity) at baseline with patient-reported SCCAI every 2 weeks over 1 to 2 years and fecal calprotectin at time of flare. Clinical flares (SCCAI ≥5) and biochemical flares (SCCAI ≥5 with fecal calprotectin ≥250 µg/g) were evaluated. RESULTS: One hundred ten patients with UC were enrolled, with mean follow-up of 65.6 weeks. Patients with UC with higher and lower PS were determined. Although the high PS group had 3.6 times higher odds of a clinical flare than the low PS group, no significant differences in biochemical flares were observed between the low and high PS groups. The high vs low PS group differed in tonic sympathetic arousal as indexed by significantly greater baseline electrodermal activity (4.3 vs 3.4 microsiemens; P = .026) in the high PS group, but not in terms of heart rate variability and morning cortisol levels. Increased fecal calprotectin was associated with cardioautonomic measures, suggesting lower parasympathetic activity. CONCLUSIONS: Increased PS assessed at baseline is associated with tonic sympathetic arousal and greater odds of clinical flares in patients with UC.


Assuntos
Colite Ulcerativa , Estresse Psicológico , Exacerbação dos Sintomas , Humanos , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/psicologia , Fezes/química , Hidrocortisona , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/psicologia , Complexo Antígeno L1 Leucocitário , Estresse Psicológico/fisiopatologia
3.
J Ethnopharmacol ; 289: 115056, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35104576

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lepidium virginicum L. (Brassicaceae) is a plant widely used in traditional Mexican medicine as an expectorant, diuretic, and as a remedy to treat diarrhea and dysentery, infection-derived gastroenteritis. However, there is no scientific study that validates its clinical use as an anti-inflammatory in the intestine. AIM OF THE STUDY: This study aimed to investigate the anti-inflammatory properties of the ethanolic extract of Lepidium virginicum L. (ELv) in an animal model of inflammatory bowel disease (IBD)-like colitis. MATERIALS AND METHODS: The 2,4-dinitrobenzene sulfonic acid (DNBS) animal model of IBD was used. Colitis was induced by intrarectal instillation of 200 mg/kg of DNBS dissolved vehicle, 50% ethanol. Control rats only received the vehicle. Six hours posterior to DNBS administration, ELv (3, 30, or 100 mg/kg) was administered daily by gavage or intraperitoneal injection. The onset and course of the inflammatory response were monitored by assessing weight loss, stool consistency, and fecal blood. Colonic damage was evaluated by colon weight/length ratio, histopathology, colonic myeloperoxidase (MPO) activity, and gene expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), chemokine C-X-C motif ligand 1 (CXCL-1), and interleukin-6 (IL-6). RESULTS: Rats treated with DNBS displayed significant weight loss, diarrhea, fecal blood, colon shortening, a significant increase in immune cell infiltration and MPO activity, as well as increased proinflammatory cytokine expression. Intraperitoneal administration of ELv significantly reduced colon inflammation, whereas oral treatment proved to be ineffective. In fact, intraperitoneal ELv significantly attenuated the clinical manifestations of colitis, immune cell infiltration, MPO activity, and pro-inflammatory (CXCL-1, TNF-α, and IL-1ß) gene expression in a dose-dependent manner. CONCLUSION: Traditional medicine has employed ELv as a remedy for common infection-derived gastrointestinal symptoms; however, we hereby present the first published study validating its anti-inflammatory properties in the mitigation of DNBS-induced colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Lepidium/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Colite/genética , Colite/fisiopatologia , Dinitrofluorbenzeno/análogos & derivados , Relação Dose-Resposta a Droga , Etanol/química , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/fisiopatologia , Medicina Tradicional , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar
4.
PLoS One ; 17(2): e0264194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35192646

RESUMO

Physical and chemical methods for generating rat models of enteritis have been established; however, antibiotic induction has rarely been used for this purpose. The present study aimed to establish and evaluate a rat model of inflammatory bowel disease (IBD) using antibiotics. A total of 84 Sprague-Dawley (SD) rats were divided into the following groups, according to the dosage and method of administration of the antibiotics: A, control; B, low-dose clindamycin; C, medium-dose clindamycin; D, high-dose clindamycin; E, low-dose clindamycin, ampicillin and streptomycin; F, medium-dose clindamycin, ampicillin and streptomycin; and G, high-dose clindamycin, ampicillin and streptomycin. Antibiotic administration was stopped on day 7; the modeling period covered days 1-7, and the recovery period covered days 8-15. Half of the animals were dissected on day 11, with the remaining animals dissected on day 15. Food and water intake, body weight and fecal weight were recorded. Intestinal flora was analyzed via microbial culture and quantitative PCR. The content of TNF-α, IL1-ß, IL-6 and C-reactive protein (CRP) was assessed in abdominal aorta blood. Colonic and rectal tissues were examined pathologically via hematoxylin-eosin staining to assess leukocyte infiltration and intestinal mucosal changes as indicators of inflammation. Rat weight, food intake, water intake and 2-h fecal weight were significantly different across the experimental groups (P = 0.040, P = 0.016, P<0.001 and P = 0.009, respectively). Microbial cultures revealed no significant differences between group A and B,C (P = 0.546,0.872) but significant differences betwenn group A and the other experimental groups (all P<0.001). Furthermore, significant differences in the levels of Bacteroides, Faecalibacterium prausnitzii and Dialister invisus on day 4 between groups A, C and F (P = 0.033, P = 0.025 and P = 0.034, respectively). Significant differences were detected in the levels of TNF-α, IL1-ß, IL-6 and CRP between the groups (all P<0.001). The colonic and rectal pathological inflammation scores of the experimental groups were significantly different compared with group A (B vs. A, P = 0.002; others, all P<0.001). These findings indicated that an antibiotic-induced IBD model was successfully established in SD rats; this animal model may serve as a useful model for clinical IBD research.


Assuntos
Antibacterianos/toxicidade , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/fisiopatologia , Animais , Proteína C-Reativa/metabolismo , Feminino , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/metabolismo , Interleucinas/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
5.
J Neuroinflammation ; 19(1): 4, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983592

RESUMO

Patients with inflammatory bowel disease (IBD) suffer from depression at higher rates than the general population. An etiological trigger of depressive symptoms is theorised to be inflammation within the central nervous system. It is believed that heightened intestinal inflammation and dysfunction of the enteric nervous system (ENS) contribute to impaired intestinal permeability, which facilitates the translocation of intestinal enterotoxins into the blood circulation. Consequently, these may compromise the immunological and physiological functioning of distant non-intestinal tissues such as the brain. In vivo models of colitis provide evidence of increased blood-brain barrier permeability and enhanced central nervous system (CNS) immune activity triggered by intestinal enterotoxins and blood-borne inflammatory mediators. Understanding the immunological, physiological, and structural changes associated with IBD and neuroinflammation may aid in the development of more tailored and suitable pharmaceutical treatment for IBD-associated depression.


Assuntos
Eixo Encéfalo-Intestino/fisiologia , Depressão/etiologia , Doenças Inflamatórias Intestinais/etiologia , Doenças Neuroinflamatórias/complicações , Depressão/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Neuroinflamatórias/fisiopatologia
6.
Adv Drug Deliv Rev ; 181: 114101, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34999122

RESUMO

The complex pathogenesis of inflammatory bowel disease (IBD) explains the several hurdles for finding an efficient approach to cure it. Nowadays, therapeutic protocols aim to reduce inflammation during the hot phase or maintain remission during the cold phase. Nonetheless, these drugs suffer from severe side effects or poor efficacy due to low bioavailability in the inflamed region of the intestinal tract. New protocols based on antibodies that target proinflammatory cytokines are clinically relevant. However, besides being expensive, their use is associated with a primary nonresponse or a loss of response following a long administration period. Accordingly, many researchers exploited the physiological changes of the mucosal barrier for designing nanoparticulate drug delivery systems to target inflamed tissues. Others exploited biocompatibility and relative affordability of polysaccharides to test their intrinsic anti-inflammatory and healing properties in IBD models. This critical review updates state of the art on advances in IBD treatment. Data on using polysaccharide nanoparticulate drug delivery systems for IBD treatment are reviewed and discussed.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/fisiopatologia , Sistemas de Liberação de Fármacos por Nanopartículas/farmacologia , Polissacarídeos/farmacologia , Administração Oral , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Concentração de Íons de Hidrogênio , Mediadores da Inflamação/fisiologia , Muco/metabolismo , Polissacarídeos/administração & dosagem
7.
PLoS One ; 17(1): e0262571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35061808

RESUMO

BACKGROUNDS AND AIMS: Inflammatory bowel disease (IBD) patients often experience disease flare-ups during international air travel. We aimed to identify risk factors associated with IBD flare-up during international air travel. METHODS: Patients with scheduled international air travel were enrolled in the study from the Seoul National University Bundang Hospital IBD clinic. Flight information and clinical data were collected via questionnaires and personal interviews, and risk factors associated with IBD flares were determined. RESULTS: Between May 2018 and February 2020, 94 patients were prospectively enrolled in the study (mean age, 33.0 years; males, 53.2%; mean disease duration, 56.7 months), including 56 (59.6%) with ulcerative colitis and 38 (40.4%) with Crohn's disease. Of the 94 patients enrolled, 15 (16.0%) experienced an IBD flare-up and 79 (84.0%) remained in remission throughout travel. Logistic regression analysis revealed that high fecal calprotectin levels before travel (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000-1.001, p = 0.016), the presence of a comorbidity (OR: 6.334, 95% CI: 1.129-35.526, p = 0.036), and history of emergency room visit (OR: 5.283, 95% CI: 1.085-25.724, p = 0.039) were positively associated with disease flare-up. The previous and current use of immunomodulators and biologics, time of flight, altitude, number countries visited, travel duration, objective of visit, and previous medical consultations were not associated with disease flare-up. CONCLUSIONS: Elevated fecal calprotectin levels, history of emergency room visits, and the presence of a comorbidity predicted IBD flare-up during international air travel.


Assuntos
Doenças Inflamatórias Intestinais/fisiopatologia , Exacerbação dos Sintomas , Adulto , Viagem Aérea , Colite/etiologia , Colite/fisiopatologia , Colite Ulcerativa/etiologia , Colite Ulcerativa/fisiopatologia , Doença de Crohn/etiologia , Doença de Crohn/fisiopatologia , Fezes/química , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Complexo Antígeno L1 Leucocitário/análise , Masculino , Prognóstico , Estudos Prospectivos
8.
Food Funct ; 13(2): 514-529, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34935814

RESUMO

Intestinal inflammation represented by inflammatory bowel disease (IBD) has become a global epidemic disease and the number of patients with IBD continues to increase. This digestive tract disease not only affects the absorption of food components by destroying the intestinal epithelial structure, but also can induce diseases in remote organs via the gut-organ axis, seriously harming human health. Nowadays, increasing attention is being paid to the nutritional and medicinal value of food components with increasing awareness among the general public regarding health. As an important member of the isothiocyanates, sulforaphane (SFN) is abundant in cruciferous plants and is famous for its excellent anti-cancer effects. With the development of clinical research, more physiological activities of SFN, such as antidepressant, hypoglycemic and anti-inflammatory activities, have been discovered, supporting the fact that SFN and SFN-rich sources have great potential to be dietary supplements that are beneficial to health. This review summarizes the characteristics of intestinal inflammation, the anti-inflammatory mechanism of SFN and its various protective effects on intestinal inflammation, and the possible future applications of SFN for promoting intestinal health have also been discussed.


Assuntos
Anti-Inflamatórios , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Isotiocianatos , Sulfóxidos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Brassicaceae , Colite/metabolismo , Colite/microbiologia , Colite/fisiopatologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Isotiocianatos/química , Isotiocianatos/metabolismo , Isotiocianatos/farmacologia , Camundongos , Sulfóxidos/química , Sulfóxidos/metabolismo , Sulfóxidos/farmacologia , Verduras
9.
United European Gastroenterol J ; 10(1): 104-114, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34939350

RESUMO

BACKGROUND: Educating patients regarding thier inflammatory bowel disease (IBD) is important for their empowerment and disease management. We aimed to develop a questionnaire to evaluate patient understanding and knowledge of IBD. METHODS: We have developed the Understanding IBD Questionnaires (U-IBDQ), consisting of multiple-choice questions in two versions [for Crohn's disease (CD) and ulcerative colitis (UC)]. The questionnaires were tested for content and face validity, readability, responsiveness and reliability. Convergent validity was assessed by correlating the U-IBDQ score with physician's subjective assessment scores. Discriminant validity was assessed by comparison to healthy controls (HC), patients with chronic gastrointestinal (GI) conditions other than IBD, and to GI nurses. Multivariate analysis was performed to determine factors associated with a high level of disease understanding. RESULTS: The study population consisted of IBD patients (n = 106), HC (n = 35), chronic GI disease patients (n = 38) and GI nurses (n = 19). Mean U-IBDQ score among IBD patients was 56.5 ± 21.9, similar for CD and UC patients (P = 0.941), but significantly higher than that of HC and chronic GI disease patients and lower than that of GI nurses (P < 0.001), supporting its discriminant validity. The U-IBDQ score correlated with physician's subjective score (r = 0.747, P < 0.001) and was found to be reliable (intra-class correlation coefficient = 0.867 P < 0.001). Independent factors associated with high U-IBDQ scores included academic education (OR = 1.21, 95% CI 1.10-1.33, P < 0.001), biologic therapy experience (OR = 1.24, 95% CI 1.01-1.53, P = 0.046), and IBD diagnosis at <21 years of age (OR = 2.97, 95% CI 1.05-8.87, P = 0.050). CONCLUSIONS: The U-IBDQ is a validated, reliable and short, self-reported questionnaire that can be used for assessing understanding of disease pathophysiology and treatment by IBD patients.


Assuntos
Colite Ulcerativa , Doença de Crohn , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto , Inquéritos e Questionários , Adulto , Fatores Etários , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/terapia , Compreensão , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Análise Discriminante , Feminino , Gastroenteropatias , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recursos Humanos de Enfermagem no Hospital/estatística & dados numéricos , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Adulto Jovem
10.
Dig Liver Dis ; 54(3): 309-315, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34866011

RESUMO

BACKGROUND AND AIMS: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD. METHODS: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement. RESULTS: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient. CONCLUSION: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients.


Assuntos
Gastroenterologia/normas , Doenças Inflamatórias Intestinais/fisiopatologia , Nefropatias/etiologia , Testes de Função Renal/normas , Guias de Prática Clínica como Assunto , Consenso , Humanos , Doenças Inflamatórias Intestinais/complicações , Rim/fisiopatologia
11.
Biomed Pharmacother ; 145: 112414, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34808552

RESUMO

Inflammatory bowel diseases, irritable bowel syndrome, and mucositis are characterized by intestinal inflammation, but vary according to their pathological mechanisms, severity, location, and etiology. Significant intestinal inflammation that occurs in these diseases induces weight loss, nutritional depletion, and gastrointestinal tract dysfunction. Nutritional support is important in alleviating symptoms and improving patients' quality of life. In this review, we summarize some nutritional components used to manage intestinal disorders. These include fatty acids, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and low FODMAP (LFD) diets. These components and LFD diets have been studied and clinical trials have been designed to develop new strategies to alleviate intestinal inflammation and improve the quality of life. Clinical trials on their use in intestinal inflammation do not allow firm conclusions to be drawn mainly because of the heterogeneity of the dose used and the study design or their inconclusive results. However, in the majority of cases, the use of omega-3, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and LFD improve the health.


Assuntos
Suplementos Nutricionais , Inflamação/terapia , Enteropatias/terapia , Animais , Humanos , Inflamação/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Enteropatias/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/terapia , Mucosite/fisiopatologia , Mucosite/terapia , Apoio Nutricional/métodos , Qualidade de Vida
12.
J Ethnopharmacol ; 283: 114749, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34666140

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Baicalin (BI) is an important biologically active flavonoid isolated from the root of Scutellaria radix (Huang Qin). Traditionally Scutellaria radix was the common drug of dysentery. As the main flavonoid compound, there is a distribution tendency of baicalin to the intestinal tract and it has a protective effect on the gastrointestinal tract. AIM OF THE REVIEW: This review aims to compile up-to-date and comprehensive information on the efficacy of baicalin in vitro and in vivo, about treating inflammatory bowel disease. Relevant information on the therapeutic potential of baicalin against inflammatory bowel disease was collected from the Web of Science, Pubmed and so on. Additionally, a few books and magazines were also consulted to get the important information. RESULTS: The mechanisms of baicalin against inflammatory bowel disease mainly include anti-inflammation, antioxidant, immune regulation, maintenance of intestinal barrier, maintenance of intestinal flora balance. Also, BI can relieve parts of extraintestinal manifestations (EIMs), and prevent colorectal cancer. CONCLUSION: Baicalin determined the promising therapeutic prospects as potential supplementary medicines for the treatment of IBD.


Assuntos
Flavonoides/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Scutellaria baicalensis/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/isolamento & purificação , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia
13.
Gastroenterol Hepatol ; 45(1): 66-76, 2022 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34023477

RESUMO

The presence of digestive symptoms associated with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in remission is a topic of growing interest. Although there is heterogeneity in clinical studies regarding the use of IBD remission criteria and the diagnosis of IBS, the available data indicate that the IBD-IBS overlap would affect up to one third of patients in remission, and they agree on the finding of a negative impact on the mental health and quality of life of the individuals who suffer from it. The pathophysiological bases that would explain this potential overlap are not completely elucidated; however, an alteration in the gut-brain axis associated with an increase in intestinal permeability, neuroimmune activation and dysbiosis would be common to both conditions. The hypothesis of a new clinical entity or syndrome of "Irritable Inflammatory Bowel Disease" or "Post-inflammatory IBS" is the subject of intense investigation. The clinical approach is based on certifying the remission of IBD activity and ruling out other non-inflammatory causes of potentially treatable persistent functional digestive symptoms. In the case of symptoms associated with IBS and in the absence of sufficient evidence, comprehensive and personalized management of the clinical picture (dietary, pharmacological and psychotherapeutic measures) should be carried out, similar to a genuine IBS.


Assuntos
Eixo Encéfalo-Intestino/fisiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Disbiose , Motilidade Gastrointestinal/fisiologia , Humanos , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/terapia , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/psicologia , Síndrome do Intestino Irritável/terapia , Qualidade de Vida , Indução de Remissão , Síndrome
14.
Dig Dis Sci ; 67(2): 622-628, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33932198

RESUMO

BACKGROUND: Frailty may be a risk factor for complications in inflammatory bowel diseases (IBD) patients. We examined the impact of treatment on IBD patients who were frail prior to treatment and identified predictors of post-treatment change in frailty. METHODS: In an electronic health record-based cohort of IBD patients initiating anti-tumor necrosis factor (TNF)-α agents, we applied a validated claims-based frailty index to determine frailty in the 1 year prior to and after treatment initiation. We characterized treatment non-response using a composite outcome of IBD-related hospitalization, surgery, change in therapy, or initiation of systemic steroids. We constructed multivariable logistic regression models to identify determinants of post-treatment frailty. RESULTS: The 1210 patients initiating anti-TNF therapy had a median age of 30 years; 20% were ≥ 50 years. In the first year after anti-TNF initiation, 40% were non-responders. Many more treatment non-responders were frail in the year following treatment compared with treatment responders (27% vs 7%, p < 0.001). Pre-treatment frailty (OR 2.01, 95% CI 1.35-3.00) and prior IBD-related hospitalization (OR 1.63, 95% CI 1.15-2.30) were independently predictive of higher likelihood of post-treatment frailty. Therapy response was associated with a lower likelihood (OR 0.24, 95% CI 0.16-0.34) of post-treatment frailty. Nearly 85% of patients who were frail prior to treatment demonstrated improvement in frailty following treatment CONCLUSIONS: Response to anti-TNF therapy is an important determinant of post-treatment frailty in patients with IBD. Our findings suggest that effectively treating inflammatory states in older patients with IBD may improve frailty.


Assuntos
Fragilidade/fisiopatologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Adulto , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/fisiopatologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Feminino , Fragilidade/complicações , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Infliximab/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Resultado do Tratamento , Adulto Jovem
15.
Dig Dis Sci ; 67(2): 457-462, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33721160

RESUMO

BACKGROUND: IBD, both Crohn's disease and ulcerative colitis, is associated with significant functional disability. Gastrointestinal symptoms alone are not the sole purpose of the interaction between patients and providers. In order to ascertain patients' disabilities, we utilized the recently developed IBD Disk to help determine their functional concerns and initiate relevant conversation. We aimed to ascertain patient acceptability and their major disabilities. PATIENTS AND METHODS: In this multicenter study, IBD patients at their outpatient visit were given the paper version of the IBD Disk. Patients were asked to score their level of disability for each item of the IBD Disk. The completed scores were then shared with their healthcare provider to act as a focus of discussion during the consultation. Patients and clinicians were also asked to provide informal qualitative feedback as to the benefits of the IBD Disk and areas for improvement. RESULTS: A total of 377 (female 60%) patients completed the questionnaires over the study period. Patient acceptability scored on a 0-10 Likert scale was excellent. All patients scored all domains of disability. Sleep, energy, and joint pain were the highest scoring domains of the IBD Disk, scoring higher than digestive symptoms. Clinicians and patients agreed that the IBD Disk allowed for ease of communication about disability symptoms and relevance to their day-to-day functioning. CONCLUSION: The IBD Disk is a novel easy-to-use tool to assess the functional disability of patients. We next plan to utilize it in the form of an electronic app internationally and in relation to treatment commencement and escalation.


Assuntos
Dor Abdominal/fisiopatologia , Artralgia/fisiopatologia , Atitude do Pessoal de Saúde , Fadiga/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Aceitação pelo Paciente de Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Transtornos do Sono-Vigília/fisiopatologia , Adulto , Estudos de Viabilidade , Feminino , Gastroenterologistas , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Inquéritos e Questionários
16.
Dig Dis Sci ; 67(2): 639-645, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33638748

RESUMO

BACKGROUND: While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in disease initiation and progression. Currently, there is no convenient way to measure this in vivo. AIMS: Our aim is to determine whether a mucosal integrity (MI) testing device that has been used to measure MI in the esophagus can also be used to measure barrier function in the colon during colonoscopy. METHODS: Mucosal integrity testing was measured in patients with IBD (n = 17) and controls (n = 7) during colonoscopy. During the procedure, an MI catheter was passed down the working channel of the colonoscope and placed along the mucosal wall to measure MI in the rectum, left, transverse, and right colon. In patients with IBD, MI measurements and biopsies were taken in areas which appeared inflamed when present. We then determined if there was a significant difference in MI between patients with IBD and controls. RESULTS: MI was significantly higher in the rectum of patients with IBD (CD and UC combined) versus control colons [767 (618-991) vs. 531 (418-604) ohms, P < 0.01]. There were no significant differences in MI among patients with IBD versus controls in the right, transverse, or left colon. Within the IBD group, there were no significant differences in MI between inflamed versus non-inflamed rectums. There was no correlation between quality of life scores or endoscopic severity with MI, though this study was likely underpowered to detect these differences. CONCLUSION: Rectal MI is significantly higher in patients with IBD versus controls. Future studies are needed to determine how this information can be used clinically.


Assuntos
Colo/fisiopatologia , Impedância Elétrica , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/fisiopatologia , Reto/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Colo/fisiologia , Colonoscopia , Feminino , Humanos , Mucosa Intestinal/fisiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reto/fisiologia
17.
Nat Commun ; 12(1): 7294, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911964

RESUMO

Recruitment of bone marrow derived monocytes via bloodstream and their subsequent conversion to CX3CR1+ macrophages in response to intestinal injury is dependent on CCR2, Nr4a1, and the microbiome. This process is critical for proper tissue repair; however, GATA6+ peritoneal cavity macrophages might represent an alternative, more readily available source of mature and functional myeloid cells at the damaged intestinal locations. Here we show, using spinning-disk confocal microscopy, that large F4/80hiGATA6+ peritoneal cavity macrophages promptly accumulate at damaged intestinal sites upon intestinal thermal injury and upon dextran sodium sulfate induced colitis in mice via a direct route from the peritoneal cavity. In contrast to bloodstream derived monocytes/macrophages, cavity macrophages do not depend on CCR2, Nr4a1 or the microbiome for recruitment, but rather on the ATP-release and exposed hyaluronan at the site of injury. They participate in the removal of necrotic cells, revascularization and collagen deposition and thus resolution of tissue damage. In summary, peritoneal cavity macrophages represent a rapid alternative route of intestinal tissue repair to traditional monocyte-derived macrophages.


Assuntos
Fator de Transcrição GATA6/imunologia , Doenças Inflamatórias Intestinais/imunologia , Macrófagos Peritoneais/imunologia , Peritônio/imunologia , Animais , Fator de Transcrição GATA6/genética , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/fisiopatologia , Intestinos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/imunologia , Receptores CCR2/genética , Receptores CCR2/imunologia , Regeneração
18.
Gut Microbes ; 13(1): 1990827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34747326

RESUMO

Intestinal epithelium represents a dynamic and diverse cellular system that continuously interacts with gut commensals and external cues. Intestinal stem cells, which lie at the heart of epithelial renewal and turnover, proliferate to maintain a steady stem cell population and differentiate to form functional epithelial cell types. This rather sophisticated assembly-line is maintained by an elaborate micro-environment, sculpted by a myriad of host and gut microbiota-derived signals, forming an intestinal stem cell niche. This complex, yet crucial signaling niche undergoes dynamic changes during homeostasis and chronic intestinal inflammation. Inflammatory bowel disease refers to a chronic inflammatory response toward pathogenic or commensal microbiota, in a genetically susceptible host. Compositional and functional alterations in gut microbiota are pathognomonic of IBD.The present review highlights the modulatory role of gut microbiota on the intestinal stem cell niche during homeostasis and inflammatory bowel disease. We discuss the mechanisms of direct action of gut commensals (through microbiota-derived or microbiota-influenced metabolites) on ISCs, followed by their effects via other epithelial and immune cell types.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/citologia , Nicho de Células-Tronco , Animais , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/microbiologia , Células-Tronco/citologia , Células-Tronco/metabolismo
19.
Biomed Res Int ; 2021: 2294942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820453

RESUMO

lncRNA is a transcript that is more than 200 bp in length. Currently, evidence has shown that lncRNA is of great significance in cell activity, involved in epigenetics, gene transcription, chromatin regulation, etc. The existence of an intestinal mucosal mechanical barrier hinders the invasion of pathogenic bacteria and toxins, maintaining the stability of the intestinal environment. Serious destruction or dysfunction of the mechanical barrier often leads to intestinal diseases. This review first summarizes the ability of lncRNAs to regulate the intestinal mucosal mechanical barrier. We then discussed how lncRNAs participate in various intestinal diseases by regulating the intestinal mucosal mechanical barrier. Finally, we envision its potential as a new marker for diagnosing and treating intestinal inflammatory diseases.


Assuntos
Mucosa Intestinal/fisiologia , RNA Longo não Codificante/genética , Animais , Fenômenos Biomecânicos , Neoplasias Colorretais/genética , Neoplasias Colorretais/fisiopatologia , Expressão Gênica , Marcadores Genéticos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/lesões , Mucosa Intestinal/microbiologia , Modelos Biológicos , Permeabilidade , Receptores de Calcitriol/genética
20.
Int J Mol Sci ; 22(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34768752

RESUMO

For a significant proportion of patients with inflammatory bowel disease (IBD), primary non-response and secondary loss of response to treatment remain significant issues. Anti-tumor necrosis factor therapies have been licensed for use in IBD. Other disease-related pathways have been targeted as well, including the interleukin 12/23 axis and lymphocyte tracking. However, the need for parenteral administration and the associated costs of dispensing and monitoring all biologics remain a burden on healthcare systems and patients. Janus kinase inhibitors are small-molecule drugs that can be administered orally and are relatively inexpensive, thus offering an additional option for treating IBD. They have been shown to be effective in patients with ulcerative colitis (UC), but they are less effective in those with Crohn's disease (CD). Nonetheless, given the immune-system-based mechanism of these drugs, their safety profile remains a cause for concern. This article provides an overview of Janus kinase (JAK) inhibitors and new trends in the treatment of IBD.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Colite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Inibidores de Janus Quinases/farmacologia , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Piperidinas/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Triazóis/uso terapêutico
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