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2.
Adv Exp Med Biol ; 1278: 191-203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523449

RESUMO

Autoimmune conditions affect 23 million Americans or 7% of the US population. There are more than 100 autoimmune disorders, affecting every major organ system in humans. This chapter aims to further explain Treg dysfunction autoimmune disorders, including monogenic primary immune deficiency such as immune dysregulation polyendocrinopathy, enteropathy, X-linked inheritance (IPEX) syndrome, and polygenic autoimmune diseases with Treg dysfunction such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and food allergy. These conditions are associated with an abnormal small intestinal and colonic microbiome. Some disorders clearly improve with therapies aimed at microbial modification, including probiotics and fecal microbiota transplantation (FMT). Approaches to prevent and treat these disorders will need to focus on the acquisition and maintenance of a healthy colonic microbiota, in addition to more focused approaches at immune suppression during acute disease exacerbations.


Assuntos
Doenças Autoimunes , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Doenças Autoimunes/terapia , Disbiose , Transplante de Microbiota Fecal , Humanos , Linfócitos T Reguladores
3.
Adv Exp Med Biol ; 1278: 141-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523448

RESUMO

Mucosal surfaces are distinctive sites exposed to environmental, dietary, and microbial antigens. Particularly in the gut, the host continuously actively adapts via complex interactions between the microbiota and dietary compounds and immune and other tissue cells. Regulatory T cells (Tregs) are critical for tuning the intestinal immune response to self- and non-self-antigens in the intestine. Its importance in intestinal homeostasis is illustrated by the onset of overt inflammation caused by deficiency in Treg generation, function, or stability in the gut. A substantial imbalance in Tregs has been observed in intestinal tissue during pathogenic conditions, when a tightly regulated and equilibrated system becomes dysregulated and leads to unimpeded and chronic immune responses. In this chapter, we compile and critically discuss the current knowledge on the key factors that promote Treg-mediated tolerance in the gut, such as those involved in intestinal Treg differentiation, specificity and suppressive function, and their immunophenotype during health and disease. We also discuss the current state of knowledge on Treg dysregulation in human intestine during pathological states such as inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), graft-versus-host disease (GVHD), and colorectal cancer (CRC), and how that knowledge is guiding development of Treg-targeted therapies to treat or prevent intestinal disorders.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Humanos , Tolerância Imunológica , Recém-Nascido , Inflamação , Mucosa Intestinal , Linfócitos T Reguladores
4.
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
5.
Yonsei Med J ; 62(2): 99-108, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527789

RESUMO

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the gastrointestinal tract caused by interactions between genetic, environmental, immunological, and microbial factors. While the incidence and prevalence of IBD in Asian populations were relatively lower than those in Western countries, they appear to be gradually increasing. A Westernized diet, high socioeconomic status, improvement of hygiene, and development of vaccination could affect the increases in IBD incidence and prevalence in Asian countries. This review describes the latest trends in the incidence and prevalence of IBD in Asia. Studying the epidemiology of IBD in Asia may unravel the etiopathogenesis of and risk factors for IBD.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Ásia/epidemiologia , Grupo com Ancestrais do Continente Asiático , Humanos , Incidência , Prevalência , Fatores de Risco , Migrantes
8.
Cell Host Microbe ; 29(1): 10-12, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33444552

RESUMO

Intestinal immunoglobulin (Ig)A binds to distinct commensals and pathobionts, but do these IgA-coated bacterial communities define clinical characteristics of inflammatory disease? In this issue of Cell Host & Microbe, Shapiro et al. comprehensively analyze IgA-coated bacteria in new onset inflammatory bowel disease (IBD), revealing their potential in guiding precision therapy and diagnostic stratification.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Microbiota , Diamante , Humanos , Imunoglobulina A , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/genética
9.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431534

RESUMO

A man in his late 30s presented with a several-day history of rectal pain, discharge and bleeding associated with systemic upset. Sexual history revealed receptive anal sex with several male partners in the 2 weeks preceding his clinic visit. Examination of the perianal area was unremarkable. Proctoscopy showed evidence of non-ulcerative proctitis. Microscopy for Gram stain showed pus cells plus extracellular Gram-negative diplococci. The patient was treated for presumptive gonorrhoea and chlamydial infection with ceftriaxone, azithromycin and doxycycline. The patient failed to improve with this treatment regimen. Rectal swab results at 48 hours confirmed the causative agent to be herpes simplex virus (HSV) type 2. The patient was recalled and treated successfully with valaciclovir. This case serves as a useful reminder to clinicians to consider HSV in the differential diagnosis of sexually transmitted proctitis, in the absence of perianal or anorectal ulceration.


Assuntos
Herpes Simples/diagnóstico , Herpesvirus Humano 2/isolamento & purificação , Proctite/diagnóstico , Doenças Sexualmente Transmissíveis/diagnóstico , Adulto , Antivirais/uso terapêutico , DNA Viral/isolamento & purificação , Diagnóstico Diferencial , Gonorreia/diagnóstico , Herpes Simples/tratamento farmacológico , Herpes Simples/transmissão , Herpes Simples/virologia , Herpesvirus Humano 2/genética , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Mucosa Intestinal/virologia , Masculino , Proctite/tratamento farmacológico , Proctite/virologia , Reto/virologia , Comportamento Sexual , Doenças Sexualmente Transmissíveis/tratamento farmacológico , Doenças Sexualmente Transmissíveis/transmissão , Doenças Sexualmente Transmissíveis/virologia , Valaciclovir/uso terapêutico
10.
Lancet Gastroenterol Hepatol ; 6(3): 218-224, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33508241

RESUMO

SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success.


Assuntos
/farmacologia , Doenças Inflamatórias Intestinais , /epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Gastroenterologia/métodos , Gastroenterologia/tendências , Humanos , Hospedeiro Imunocomprometido , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/terapia , Sociedades Médicas , Reino Unido , Vacinação/métodos
12.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466734

RESUMO

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson's disease, Tourette's syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood-brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.


Assuntos
Canabinoides/farmacologia , Cannabis/química , Descoberta de Drogas , Compostos Fitoquímicos/farmacologia , Terpenos/farmacologia , Animais , Canabinoides/química , Canabinoides/uso terapêutico , Sinergismo Farmacológico , Endocanabinoides/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Receptores de Canabinoides/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Terpenos/química , Terpenos/uso terapêutico , Síndrome de Tourette/tratamento farmacológico , Síndrome de Tourette/metabolismo
13.
Zhonghua Nei Ke Za Zhi ; 60(1): 45-50, 2021 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-33397021

RESUMO

Objective: To determine the clinical features and genetic characters of patients with chronic enteropathy associated SLCO2A1 gene (CEAS). Methods: Five CEAS patients diagnosed at Peking Union Medical College Hospital from January 2012 to December 2019 were enrolled in this study. The clinical manifestations, laboratory test, radiological and endoscopic findings, gene detections, treatments and prognosis of these patients were reviewed and analyzed. Results: Five male patients presented gastrointestinal symptoms after puberty, including abdominal pain, diarrhea, intermittent melena or hematochezia, incomplete bowel obstruction, anemia, hypoalbuminemia and hypokalemia. The whole gastrointestinal tract except esophagus could be involved, especially the stomach and ileum. Intestinal lesions were characterized by multiple shallow ulcers with stenosis in the layers of mucosa and submucosa. Five patients were all accompanied with primary hypertrophic osteoarthropathy (PHO), and 1 with myelofibrosis and thoracic duct dysplasia. All patients were homozygous or compound heterozygous mutations of SLCO2A1 gene. Conventional treatment of inflammatory bowel disease and COX-2 inhibitors were ineffective. Conclusions: CEAS is an autosomal recessive genetic disease which widely involves the gastrointestinal tract, and can be associated with skin and bone involvement. There is no effective treatment for CEAS at present. CEAS is a different entity from other inflammatory gastrointestinal diseases.


Assuntos
Gastroenteropatias , Doenças Inflamatórias Intestinais , Transportadores de Ânions Orgânicos , Osteoartropatia Hipertrófica Primária , Humanos , Masculino , Úlcera
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