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1.
Artigo em Inglês | MEDLINE | ID: mdl-33572734

RESUMO

The gut-brain axis describes a complex interplay between the central nervous system and organs of the gastrointestinal tract. Sensory neurons of dorsal root and nodose ganglia, neurons of the autonomic nervous system, and immune cells collect and relay information about the status of the gut to the brain. A critical component in this bi-directional communication system is the vagus nerve which is essential for coordinating the immune system's response to the activities of commensal bacteria in the gut and to pathogenic strains and their toxins. Local control of gut function is provided by networks of neurons in the enteric nervous system also called the 'gut-brain'. One element common to all of these gut-brain systems is the expression of nicotinic acetylcholine receptors. These ligand-gated ion channels serve myriad roles in the gut-brain axis including mediating fast synaptic transmission between autonomic pre- and postganglionic neurons, modulation of neurotransmitter release from peripheral sensory and enteric neurons, and modulation of cytokine release from immune cells. Here we review the role of nicotinic receptors in the gut-brain axis with a focus on the interplay of these receptors with the gut microbiome and their involvement in dysregulation of gut function and inflammatory bowel diseases.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/fisiopatologia , Receptores Nicotínicos/fisiologia , Encéfalo/fisiologia , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Nervo Vago
3.
Inflamm Res ; 69(12): 1163-1172, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32886145

RESUMO

Gut homeostasis is a process that requires a prudent balance of host responses to the beneficial enteric microbial community and the pathogenic stimuli that can arise. The lack of this balance in the intestine can result in inflammatory bowel diseases, where the immune system dysfunctions leading to exacerbated inflammatory responses. In this process, macrophages are considered to play a pivotal role. In this review, we describe the important role of macrophages in maintaining intestinal homeostasis and we discuss how altered macrophage function may lead to inflammatory bowel diseases. The plasticity of macrophages during the gut inflammatory response shows the broad role of these cells in orchestrating not only the onset of inflammation but also its termination as well as healing and repair. Indeed, the state of macrophage polarization can be the key factor in defining the resolution or the progression of inflammation and disease. Here, we discuss the different populations of macrophages and their implication in development, propagation, control and resolution of inflammatory bowel diseases.


Assuntos
Enterite/patologia , Homeostase , Intestinos/patologia , Intestinos/fisiologia , Macrófagos/patologia , Macrófagos/fisiologia , Animais , Polaridade Celular , Humanos , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Ativação de Macrófagos
4.
Medicina (Kaunas) ; 56(8)2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823727

RESUMO

Background and objectives: Spreading of SARS-CoV-2 infection from China to countries with a higher prevalence of inflammatory bowel disease (IBD) has generated concern among gastroenterologists and patients. The aim of this survey is to evaluate knowledge about clinical importance of COVID-19, disease management, prevention measures, and anxiety level during pandemic among patients with IBD. Material and methods: From 15th March to 15th April 2020, a questionnaire survey was administered to 200 patients with IBD by email or phone application. The questionnaire consisted of five sections: (1) anthropometric, demographic and clinical characteristics, (2) knowledge about clinical importance of COVID-19, (3) IBD management, (4) prevention measures, (5) anxiety level during pandemic. Results: One hundred forty two questionnaires were completed. Ninety-seven patients (68.3%) were males with a mean age of 46 years (SD 13; range 17-76). Fifty-four individuals (38%) were affected by Crohn disease and 88 (62%) by Ulcerative Colitis. Most patients reported high knowledge about clinical importance of COVID-19 (80%), IBD management (72%), and prevention measures (97%). Sixty-two percent of them showed moderate-high level of anxiety. High education level was independently associated with high knowledge about clinical importance of COVID-19 (odds ratio [OR] 5, 95% confidence interval [CI] 1.49-16.6, p = 0.009) and older age (OR 1, 95%, CI 1.01-1.1, p = 0.01), while the receipt of e-format educational material with low knowledge about clinical importance of COVID-19 (OR 3, 95%, CI 1.08-9.3, p = 0.03). Displaying an active disease appeared to be independently associated with low knowledge of IBD management (OR 5.8, 95% CI 1.4-22.8, p = 0.01) and no variables other than an older age was independently associated with higher level of anxiety (OR 1.04, 95% CI 1.009-1.09, p = 0.01). Conclusions: High educational level and aging promote knowledge about clinical importance of COVID-19, while e-format educational material does not. Taken together with findings that an active disease status compromises knowledge of IBD management and the high level of anxiety related to increasing age, these data suggest the need of further supporting patient-oriented strategies in IBD during Covid-19 pandemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Doenças Inflamatórias Intestinais/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adolescente , Adulto , Idoso , Ansiedade , Betacoronavirus , Escolaridade , Feminino , Humanos , Controle de Infecções , Doenças Inflamatórias Intestinais/fisiopatologia , Itália , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inquéritos e Questionários , Adulto Jovem
5.
PLoS One ; 15(6): e0233654, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502199

RESUMO

BACKGROUND AND AIMS: The disease-related knowledge levels in patients with inflammatory bowel disease (IBD) are important because it could affect the self-management ability and adaptive coping strategies. We set out to determine whether higher levels of disease-related knowledge reduce medical acceleration. METHODS: We evaluated the levels of disease-related knowledge in all patients at the time of enrollment for SNUBH IBD cohort using the validated IBD-KNOW questionnaire. Clinical data were prospectively collected and the factors related to step-up therapy were analyzed. Step-up therapy was defined as the new use of corticosteroids, immunomodulators, or biologics after the enrollment. RESULTS: Between April 2017 and January 2019, 298 patients were enrolled (mean age, 39.8 years; males, 69.5%); 193 patients (64.8%) had ulcerative colitis and 105 (35.2%) had Crohn's disease. The mean disease duration was 35.8 months. During the mean follow-up of 14.7 months, 90 patients (30.2%) underwent step-up therapy and 208 (69.8%) underwent continuous therapy. The prevalence of continuous therapy increased with increasing IBD-KNOW scores (p for trend = 0.019). Cox proportional hazards analysis revealed that high IBD-KNOW scores (≥ 16) (hazards ratio [HR]: 0.498, 95% confidence interval [CI]: 0.276-0.897, p = 0.020) was negatively associated with the step-up therapy. CONCLUSIONS: Higher disease-related knowledge could reduce the requirement of step-up therapy in IBD. The IBD-KNOW score was independently predictive of step-up therapy.


Assuntos
Doenças Inflamatórias Intestinais/fisiopatologia , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Prognóstico , Estudos Prospectivos
6.
Ceska Gynekol ; 85(2): 144-148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32527110

RESUMO

OBJECTIVE: To bring actual summary of pre and perinatal care of women with Crohn's disease and ulcerative colitis. DESIGN: Review. SETTING: Department of Gynaecology and Obstetrics, General Faculty Hospital and 1st Faculty of Medicine, Prague. METHODS: Review of articles. CONCLUSION: Care of women with inflammatory bowel diseases should be placed in a specialised centre and management of pregnancy should be discussed by a multidisciplinary team included obstetrician, gastroenterologist, surgeon and nutritional specialist. All the possibilities in treatment of these women (except a few of them) are safe during the pregnancy and in the puerperium both for mother and fetus.


Assuntos
Doenças Inflamatórias Intestinais/fisiopatologia , Complicações na Gravidez/fisiopatologia , Adulto , Feminino , Humanos , Período Pós-Parto , Gravidez , Resultado da Gravidez
7.
Lancet Gastroenterol Hepatol ; 5(6): 616-624, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32416862

RESUMO

Sleep quality and sleep disorders affect symptom manifestation and the pathogenesis of digestive diseases. Sleep is largely regulated by the light-dark cycle and associated circadian rhythms. These occurrences are closely regulated through several mechanisms with direct effects on the gastrointestinal tract. Misalignment of the circadian system is a common cause of sleep complaints, which play an important role in the presentation of many gastrointestinal disorders. This Review will focus on sleep disorders and how these alterations in sleep play an important role in many commonly encountered digestive diseases, such as gastro-oesophageal reflux disease, irritable bowel syndrome, inflammatory bowel disease, and non-alcoholic fatty liver disease. Therapeutic interventions focusing on resolving sleep disorders could optimise treatment and improve quality of life in these patients.


Assuntos
Relógios Biológicos/fisiologia , Refluxo Gastroesofágico/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Ritmo Circadiano/fisiologia , Refluxo Gastroesofágico/metabolismo , Trato Gastrointestinal/fisiologia , Trato Gastrointestinal/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Síndrome do Intestino Irritável/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Sono/fisiologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologia , Transtornos do Sono-Vigília/metabolismo
8.
Aliment Pharmacol Ther ; 52(2): 276-283, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32359205

RESUMO

BACKGROUND: Data on patients with inflammatory bowel diseases (IBD) who have had 2019 novel coronavirus (SARS-CoV-2) disease (COVID-19) are needed. AIMS: To report the clinical characteristics, including gastrointestinal symptoms, of COVID-19 in IBD patients, and to assess the risk of COVID-19 in IBD. METHODS: This case series included consecutive IBD patients with laboratory-confirmed COVID-19. Age-adjusted cumulative incidences were compared with the general population in the Madrid region. RESULTS: Through April 8, 12 of 1918 IBD patients were diagnosed with COVID-19. The average age was 52 years, 75% of the patients were female and 58.3% had Crohn's disease. Seven patients (58%) were on maintenance treatment with immunomodulators/biologics, of these four with combined therapy (33%). Eight patients (66%) required hospitalisation (one intensive care unit admission, and two deaths), and four patients were isolated at home. Nine patients had diarrhoea ranging between 4 and 10 loose stools per day (mean 5.4, SD 1.6). In five patients (42%) diarrhoea was a presenting symptom. In two patients, diarrhoea was the only symptom at debut. Cumulative incidence of COVID-19 was 6.2 per 1000 IBD patients. IBD patients had a lower adjusted incidence ratio of COVID-19 (OR 0.74, 95% CI 0.70-0.77; P < 0.001), and a similar associated mortality ratio (OR 0.95, 95% CI: 0.84-1.06; P = 0.36), compared with the general population. CONCLUSIONS: IBD patients do not have an increased risk of COVID-19 and associated mortality compared with the general population. In many IBD patients, diarrhoea was a presenting symptom, and sometimes, was the only symptom at onset of COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Doença de Crohn/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Betacoronavirus/isolamento & purificação , Produtos Biológicos/administração & dosagem , Doença de Crohn/fisiopatologia , Feminino , Hospitalização , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Incidência , Doenças Inflamatórias Intestinais/fisiopatologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias
10.
Am J Gastroenterol ; 115(6): 832-840, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32224703

RESUMO

Various lifestyle factors including physical activity and obesity, stress, sleep, and smoking may modify the risk of developing inflammatory bowel diseases (IBDs). In patients with established IBD, these lifestyle factors may significantly impact the natural history and clinical outcomes. Recreational exercise decreases the risk of flare and fatigue in patients with IBD. In contrast, obesity increases the risk of relapse and is associated with higher anxiety, depression, fatigue, and pain and higher health care utilization. Obesity also modifies pharmacokinetics of biologic agents unfavorably and is associated with a higher risk of treatment failure. Sleep disturbance is highly prevalent in patients with IBD, independent of disease activity, and increases the risk of relapse and chronic fatigue. Similarly, stress, particularly perceived stress rather than major life events, may trigger symptomatic flare in patients with IBD, although its impact on inflammation is unclear. Cigarette smoking is associated with unfavorable outcomes including the risk of corticosteroid dependence, surgery, and disease progression in patients with Crohn's disease; in contrast, smoking does not significantly impact outcomes in patients with ulcerative colitis, although some studies suggest that it may be associated with a lower risk of flare. The effect of alcohol and cannabis use in patients with IBD is inconsistent, with some studies suggesting that cannabis may decrease chronic pain in patients with IBD, without a significant effect of biological remission. Although these lifestyle factors are potentially modifiable, only a few interventional studies have been conducted. Trials of structured exercise and psychological therapy including mindfulness-based therapies such as meditation and yoga and gut-directed hypnotherapy have not consistently demonstrated benefit in clinical and/or endoscopic disease activity in IBD, although may improve overall quality of life.


Assuntos
Fumar Cigarros/epidemiologia , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Exercício Físico , Fadiga/fisiopatologia , Obesidade/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , Consumo de Bebidas Alcoólicas/epidemiologia , Ansiedade/psicologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/psicologia , Colite Ulcerativa/terapia , Doença de Crohn/epidemiologia , Doença de Crohn/psicologia , Doença de Crohn/terapia , Depressão/psicologia , Progressão da Doença , Serviços de Saúde/estatística & dados numéricos , Humanos , Hipnose , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/terapia , Estilo de Vida , Uso da Maconha/epidemiologia , Meditação , Atenção Plena , Ioga
11.
Clin Immunol ; 214: 108397, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32229290

RESUMO

Psoriatic arthritis is an inflammatory arthropathy frequently associated with psoriasis and several other comorbidities. The goal of this review is to summarize the available evidence on the epidemiology, clinical implications, pathological mechanisms proposed, and screening and management recommendations for the comorbidities related with PsA. Reported comorbidities include cardiovascular disease, metabolic syndrome, obesity, diabetes mellitus, dyslipidemia, inflammatory bowel disease, fatty liver disease, uveitis, kidney disease, infections, osteoporosis, depression, central sensitization syndrome, and gout. Given that these comorbidities may affect both clinical outcomes and the management for these patients, their recognition and monitoring by all health-care providers caring for patients with psoriatic arthritis is of utmost importance.


Assuntos
Artrite Psoriásica/epidemiologia , Ansiedade/epidemiologia , Artrite Psoriásica/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Sensibilização do Sistema Nervoso Central , Comorbidade , Efeitos Psicossociais da Doença , Depressão/epidemiologia , Gota/epidemiologia , Humanos , Infecções/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Resistência à Insulina , Nefropatias/epidemiologia , Hepatopatias/epidemiologia , Hepatopatias/fisiopatologia , Programas de Rastreamento , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Neoplasias/epidemiologia , Prevalência , Risco , Uveíte/epidemiologia , Uveíte/fisiopatologia
12.
Zhonghua Nei Ke Za Zhi ; 59(3): 189-194, 2020 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-32146744

RESUMO

Objective: To analyze the clinical characteristics of patients with ankylosing spondylitis (AS) with inflammation bowel disease (IBD). Methods: AS patients fulfilling the 1984 modified New York diagnostic criteria were recruited in Chinese AS Prospective Imaging Cohort (CASPIC) consecutively from April 2016 to June 2017 in Chinese People's Liberation Army General Hospital by using smart management system for spondyloarthritis (SpAMS). The diagnosis of IBD was confirmed by tissue pathology via ileocolonoscopy. Demographic, clinical and biochemical data were collected. Results: In total, 893 patients with AS were recruited with the mean age 30.8 years. The majority were men (739, 82.8%). There were 64 (7.2%) patients concomitant with IBD. The mean age [(34.5±7.5) years vs. (30.5±8.8) years, P<0.001] was older and the disease duration [(10.8±6.9) years vs. (8.1±5.9) years, P=0.001] was longer in patients with IBD than patients without. Compared with patients without IBD, patients with IBD had more frequent involvement of the cervical spine [(21.9% (14/64) vs. 10.5% (87/829), P=0.006) and thoracic spine [29.7% (19/64) vs. 12.3% (102/829), P<0.001]. Uveitis [28.1% (18/64) vs. 16.4% (136/829), P=0.017] and psoriasis [7.8% (5/64) vs. 2.3% (19/829), P=0.009] were also more common in patients concomitant with IBD. In addition, patients with IBD had significantly higher scores in BASDAI (3.3±2.1 vs. 2.4±1.8, P<0.001), BASFI [2.2 (1.0,3.3) vs. 1.1(0.2,2.4), P<0.001)] and ASAS HI (7.1±4.3 vs. 5.3±3.7, P= 0.001) than patients without IBD. Conclusions: Compared with patients without IBD, AS patients concomitant with IBD have more severe disease activity and organ dysfunction. Furthermore, the uveitis and psoriasis are more frequently accompanied in AS patients with IBD.


Assuntos
Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/fisiopatologia , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/fisiopatologia , Adulto , China , Feminino , Humanos , Masculino , Estudos Prospectivos , Psoríase , Índice de Gravidade de Doença , Espondilartrite , Uveíte
13.
Clin Pediatr (Phila) ; 59(6): 573-579, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32146830

RESUMO

Objectives. The available literature on pulmonary disease in pediatric inflammatory bowel disease is limited. We evaluated the prevalence of pulmonary manifestations in pediatric inflammatory bowel disease and their association with disease severity. Methods. Patients completed the St. George's Respiratory Questionnaire (SGRQ), a self-reported measure of quality of life in patients with pulmonary disease. Chart review provided demographic information and Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index scores. Regression models were utilized to evaluate associations between SGRQ score and clinical risk factors. Results. The prevalence of pulmonary manifestations was 9.62% (95% confidence interval = 5.48% to -15.36%). PCDAI scores in Crohn's disease patients with pulmonary symptoms were significantly higher (SGRQ mean = 10.71 ± 10.94) than in patients without such symptoms. SGRQ score was also higher in patients with indeterminate colitis (8.64, 95% confidence interval = 0.72-16.57, P = .03), when compared with Crohn's disease. Conclusions. Additional investigations including pulmonary function tests and imaging could provide further insight into this issue.


Assuntos
Doenças Inflamatórias Intestinais/complicações , Pneumopatias/complicações , Adolescente , Adulto , Feminino , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Pneumopatias/fisiopatologia , Masculino , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , População Urbana , Adulto Jovem
14.
Curr Gastroenterol Rep ; 22(2): 8, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002666

RESUMO

PURPOSE OF REVIEW: The bidirectional relationship between sleep disorders and inflammatory bowel disease (IBD) has gained considerable attention in recent years. It has been suggested that poor sleep and fatigue are extra-intestinal manifestations of IBD. This review reports recent studies exploring subjective and objective assessments of sleep in the adult IBD population. RECENT FINDINGS: In ulcerative colitis patients, poor sleep has been independently linked to depression and poorer IBD-related quality of life. Using home polysomnography, IBD patients were shown to have less rapid eye movement sleep and Crohn's patient had increased lighter sleep. A study utilizing surveys assessing circadian rhythms described circadian misalignment in IBD patients and reported that circadian misalignment in Crohn's disease was associated with a more aggressive disease phenotype. The use of biologics may improve sleep disturbances in patients with IBD. Translational and clinical studies have reported that disturbances in sleep quality are linked to intestinal inflammation and a heighted systemic immune response. IBD patients appear to have disturbed sleep. Poor sleep is also suggested as a marker for subclinical disease activity. Recent studies have suggested circadian misalignment in IBD patients, and future studies are needed to assess these clinical implications.


Assuntos
Fadiga/etiologia , Doenças Inflamatórias Intestinais/complicações , Transtornos do Sono-Vigília/etiologia , Produtos Biológicos/uso terapêutico , Ritmo Circadiano/fisiologia , Disbiose/fisiopatologia , Fadiga/tratamento farmacológico , Fadiga/fisiopatologia , Humanos , Inflamação/fisiopatologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/fisiopatologia , Polissonografia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/fisiopatologia
15.
BMC Res Notes ; 13(1): 48, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000855

RESUMO

OBJECTIVE: The ability to accurately and efficiently quantify mouse locomotor activity is essential for evaluating therapeutic efficacy and phenotyping genetically modified mice, in particular for the research of neuromuscular diseases. Our objective is to develop a program for video tracking of mice and locomotion analysis. RESULTS: Here we describe a MATLAB program for video tracking of mice and locomotion analysis. The system is composed of a webcam, an open field, and a computer with MATLAB installed. Animal behavior is recorded by the webcam and the video is then analyzed for mouse position on each frame by a customized MATLAB code. The system has been tested for analyzing two or more mice simultaneously placed in individual chambers. The accumulative moving distance, velocity and thigmotaxis (percentage of time spending in the outer peripheral of the arena, which is commonly used as an index of anxiety) within a test period can be readily obtained. This system can be easily implemented in any laboratory as an in vivo locomotion assay to assess the neuromuscular abnormality of genetically modified animals and the impact of therapeutic interventions.


Assuntos
Locomoção/fisiologia , Gravação em Vídeo , Animais , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/fisiopatologia
16.
Pharmacol Rep ; 72(1): 135-146, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32016839

RESUMO

BACKGROUND: Inflammatory bowel disease is an intestinal disorder presented by recurrent inflammation in the gastrointestinal tract. It has been reported that modafinil, also known as an awakening drug, has anti-inflammatory characteristics. The objective of this experiment is to investigate the protective effects of modafinil on colitis induced by acetic acid in rat and the involvement of nitric oxide pathway. METHODS: Colitis was induced by intra-rectal instillation of 1 ml acetic acid (4%). After one h of colitis induction (first day), intraperitoneal injection of dexamethasone (1 mg/kg), modafinil (50, 100, and 150 mg/kg), nitric oxide synthase inhibitors (NOS)-N (G)-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg, 7-nitroindazole 40 mg/kg, and aminoguanidine 50 mg/kg-was performed and continued for 2 consecutive days. Ultimately, macroscopic, microscopic, and biochemical assessments were performed. RESULTS: While induction of colitis caused severe macroscopic lesions, administration of dexamethasone and modafinil (100 and 150 mg/kg) significantly improved macroscopic ulcers. Interestingly, the combination of modafinil with NOS inhibitors reversed the beneficial effects of modafinil on macroscopic destructions. In addition, the elevated level of interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) was decreased by modafinil. However, treatment with NOS inhibitors before modafinil neutralized the anti-inflammatory influence of modafinil. Additionally, histological disorders emerged by acetic acid in colon tissue remarkably were disappeared after treatment with modafinil. CONCLUSIONS: In conclusion, modafinil has a protective effect on injuries induced by acetic acid in the colon of rat, which is presumably via the inhibition of inflammatory cascade and mediation of NO pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Modafinila/farmacologia , Óxido Nítrico/metabolismo , Ácido Acético , Animais , Anti-Inflamatórios/administração & dosagem , Colite/tratamento farmacológico , Colite/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Modafinila/administração & dosagem , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos , Ratos Wistar
17.
Nat Rev Gastroenterol Hepatol ; 17(3): 184-192, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32071420

RESUMO

Gut-brain dysregulation has been recognized by the scientific community as being crucial to the understanding of chronic gastrointestinal conditions, and this has translated into the practice of a newly established discipline, psychogastroenterology. Along with psychotherapy, antidepressants (a subtype of central neuromodulators) have been proposed as treatments for gut-brain disorders that might benefit both psychological and gastrointestinal health. Antidepressants have been found to be effective for the treatment of comorbid anxiety and depression, pain and impaired sleep. Although the efficacy of antidepressants is well established in disorders of gut-brain interaction (DGBI), evidence is only now emerging in IBD. This Perspective discusses the use of antidepressants in DGBI and IBD, focusing on how what we have learnt about the role of antidepressants in DGBI could be applied to help optimize the management of IBD.


Assuntos
Antidepressivos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Antidepressivos/efeitos adversos , Antidepressivos/farmacologia , Encéfalo/fisiopatologia , Dor Crônica/tratamento farmacológico , Comorbidade , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/psicologia , Neurotransmissores/farmacologia , Neurotransmissores/uso terapêutico , Medição de Risco/métodos , Transtornos do Sono-Vigília/tratamento farmacológico
18.
Clin Transl Gastroenterol ; 11(1): e00120, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899693

RESUMO

In traditional medicine, Cannabis sativa has been prescribed for a variety of diseases. Today, the plant is largely known for its recreational purpose, but it may find a way back to what it was originally known for: a herbal remedy. Most of the plant's ingredients, such as Δ-tetrahydrocannabinol, cannabidiol, cannabigerol, and others, have demonstrated beneficial effects in preclinical models of intestinal inflammation. Endogenous cannabinoids (endocannabinoids) have shown a regulatory role in inflammation and mucosal permeability of the gastrointestinal tract where they likely interact with the gut microbiome. Anecdotal reports suggest that in humans, Cannabis exerts antinociceptive, anti-inflammatory, and antidiarrheal properties. Despite these reports, strong evidence on beneficial effects of Cannabis in human gastrointestinal diseases is lacking. Clinical trials with Cannabis in patients suffering from inflammatory bowel disease (IBD) have shown improvement in quality of life but failed to provide evidence for a reduction of inflammation markers. Within the endogenous opioid system, mu opioid receptors may be involved in anti-inflammation of the gut. Opioids are frequently used to treat abdominal pain in IBD; however, heavy opioid use in IBD is associated with opioid dependency and higher mortality. This review highlights latest advances in the potential treatment of IBD using Cannabis/cannabinoids or opioids.


Assuntos
Analgésicos Opioides/uso terapêutico , Canabinoides/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Maconha Medicinal/uso terapêutico , Endocanabinoides/metabolismo , Sistema Nervoso Entérico , Microbioma Gastrointestinal , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/fisiopatologia , Uso da Maconha , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Peptídeos Opioides/metabolismo , Receptores de Canabinoides/metabolismo , Receptores Opioides mu/metabolismo , Automedicação
19.
Am J Med ; 133(1): 39-43, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398306

RESUMO

Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease.


Assuntos
Doenças Inflamatórias Intestinais/complicações , Pneumopatias/etiologia , Bronquiectasia/etiologia , Bronquiectasia/fisiopatologia , Bronquiolite/etiologia , Bronquiolite/fisiopatologia , Bronquite Crônica/etiologia , Bronquite Crônica/fisiopatologia , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/fisiopatologia , Pneumopatias/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pleurisia/etiologia , Pleurisia/fisiopatologia , Eosinofilia Pulmonar/etiologia , Eosinofilia Pulmonar/fisiopatologia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/fisiopatologia , Traqueíte/etiologia , Traqueíte/fisiopatologia , Inibidores do Fator de Necrose Tumoral/efeitos adversos
20.
Gut Liver ; 14(1): 7-19, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30919602

RESUMO

The current goal of inflammatory bowel disease (IBD) treatment is a symptom-free everyday life accompanied by mucosal healing with minimal use of corticosteroids. Recent therapeutic advances, particularly, the emergence of anti-tumor necrosis factor (anti-TNF) antibodies, have changed the natural history of IBD. Additionally, these advances also led to the emergence of the therapeutic concept of the "treat to target" strategy. With the development of new drugs and clinical trials, not only biologics but also small molecules have been applied to clinical practice to better individualize and optimize therapy. However, if newer drugs, including anti-TNF therapies, are recommended for all patients diagnosed with IBD, a significant number of patients will be overtreated. The basic goal of IBD treatment is still to make the best use of conventional treatments based on IBD pathophysiology. Thus, physicians should be familiar with the modes of action of the available drugs. In this review, the author discusses the existing data for many approved drugs and provide insights for optimizing current treatments for the management of patients with IBD in the era of biologics.


Assuntos
Produtos Biológicos/uso terapêutico , Imunoterapia/tendências , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/fisiopatologia
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