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1.
BMC Gastroenterol ; 13: 96, 2013 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-23721294

RESUMEN

BACKGROUND: An association between eosinophilic esophagitis (EoE) and celiac disease (CD) has been suggested in the literature. Our aim was to confirm and quantify the association between these two diseases. METHODS: All patients in a large Canadian city diagnosed with EoE or CD over a five-year period were identified. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Over the five-year study EoE was diagnosed in 421 patients and CD was diagnosed in 763 patients. The incidence of EoE ranged from 2.1 to 10.7 cases per 100,000 population. The incidence of CD ranged from 10.4 to 15.7 cases per 100,000 population. Among the EoE cohort, 83 (20%) cases of EoE and 245 (32%) cases of CD were diagnosed in pediatric patients. The incidence of EoE in the pediatric subpopulation ranged from 3.7 to 6.9 cases per 100,000 population. The incidence of CD in the pediatric subpopulation ranged from 9.5 to 22.7 cases per 100,000 population. The concomitant diagnosis of both EoE and CD was made in three patients, all of whom were pediatric males. The SIR for EoE in the CD cohort was 48.4 (95% CI = 9.73, 141.41) with a SIR for CD within the paediatric EoE cohort of 75.05 (95% CI = 15.08, 219.28). CONCLUSIONS: This study confirms the association between EoE and CD. However, this association may be limited to pediatrics where the risk of each condition is increased 50 to 75-fold in patients diagnosed with the alternative condition. The concomitant diagnosis of these conditions should be considered in pediatric patients with upper gastrointestinal symptoms.


Asunto(s)
Enfermedad Celíaca/epidemiología , Esofagitis Eosinofílica/epidemiología , Adolescente , Adulto , Factores de Edad , Alberta/epidemiología , Niño , Estudios de Cohortes , Intervalos de Confianza , Femenino , Humanos , Incidencia , Masculino , Adulto Joven
2.
Cytokine ; 57(2): 201-9, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22178716

RESUMEN

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, which presents with one or more gastrointestinal symptoms without any structural or organic abnormality. The etiology and pathophysiological mechanisms of IBS remain uncertain. Residual or reactivated inflammation at the molecular level is considered the underlying mechanism of post-infectious IBS. On the other hand, genetic variations in the immunological components of the body, including cytokine gene polymorphisms, are proposed as a potential mechanism of IBS even in patients without previous gastrointestinal infection. Several studies have suggested imbalanced cytokine signaling as an etiology for IBS. In this review, recent findings on cytokine profiles and cytokine gene polymorphisms in patients with IBS are described and the role of cytokines in animal models of IBS is discussed.


Asunto(s)
Citocinas/inmunología , Síndrome del Colon Irritable/inmunología , Síndrome del Colon Irritable/fisiopatología , Animales , Citocinas/clasificación , Citocinas/genética , Modelos Animales de Enfermedad , Motilidad Gastrointestinal/fisiología , Humanos , Síndrome del Colon Irritable/genética , Síndrome del Colon Irritable/psicología
3.
Clin Gastroenterol Hepatol ; 9(10): 881-90, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21699817

RESUMEN

BACKGROUND & AIMS: The incidence of microscopic colitis and its disease burden are increasing, yet there is limited systematic information addressing the use of conventional corticosteroids and budesonide in microscopic colitis. We performed a systematic review and meta-analysis on the short- and long-term efficacy of corticosteroids in treatment of microscopic colitis. METHODS: Randomized controlled trials that met predetermined selection criteria were included. Articles were identified through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, proceedings of major gastroenterology meetings, and reference lists of trials and review articles. RESULTS: Eight randomized trials were identified. A total of 248 patients were randomized to corticosteroid versus placebo. The intervention was budesonide in 7 trials and prednisolone in 1 trial. Budesonide was significantly more effective than placebo for short-term clinical response (risk ratio [RR], 3.07; 95% confidence interval [CI], 2.06-4.57) and long-term clinical response (RR, 3.22; 95% CI, 1.05-9.89). Prednisolone was not superior to placebo for short-term clinical response (RR, 2.00; 95% CI, 0.38-10.58). Histologic improvement was seen with both short- and long-term budesonide (RR, 3.76; 95% CI, 2.00-7.06, and RR, 2.50; 95% CI, 1.25-4.98, respectively). Symptom relapse occurred in 46%-80% of patients within 6 months of treatment cessation. Withdrawal because of adverse effects occurred in 4.4% of patients, with no difference between study groups (P = .55). CONCLUSIONS: Both short- and long-term treatment with budesonide is effective and well-tolerated for microscopic colitis. However, the rate of symptom relapse once budesonide is discontinued is high. Further studies are needed to determine optimal treatment duration, dose, and withdrawal procedure.


Asunto(s)
Antiinflamatorios/administración & dosificación , Budesonida/administración & dosificación , Colitis Microscópica/tratamiento farmacológico , Prednisolona/administración & dosificación , Antiinflamatorios/efectos adversos , Budesonida/efectos adversos , Humanos , Prednisolona/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Resultado del Tratamiento
4.
Br Med Bull ; 100: 59-72, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22012125

RESUMEN

BACKGROUND: Primary eosinophilic gastrointestinal disorders, a spectrum of inflammatory conditions, occurs when eosinophils selectively infiltrate the gut in the absence of known causes for such tissue eosinophilia. These may be classified into eosinophilic esophagitis, eosinophilic gastroenteritis and eosinophilic colitis (EC). This review focuses on EC: its pathogenesis, epidemiology, clinical presentation, diagnosis and current approach to treatment. SOURCES OF DATA: A literature review published in English was performed using Pubmed, Ovid, Google scholar search engines with the following keywords: eosinophilic gastrointestinal disorder, EC, eosinophils, colitis and gastrointestinal. AREAS OF AGREEMENT: The basis for primary EC appears related to increased sensitivity to allergens, principally as a food allergy in infants and a T lymphocyte-mediated event in adults. Endoscopic changes are generally modest, featuring edema and patchy granularity. AREAS OF CONTROVERSY: Clear clinical and pathological diagnostic criteria of EC and its management strategy. GROWING POINTS: Intestinal involvement of EC is primarily mucosal, presenting as a mild self-limited proctitis in infants and self-limited colitis in young adults. Therapeutic approaches based on case reports tend to use either elimination diets to avoid a presumed allergen; agents traditionally used in inflammatory disease or targeted drugs like anti-histamines or leukotriene receptor antagonists. AREAS TIMELY FOR DEVELOPING RESEARCH: Prospective randomized controlled trials addressing the disease natural history, possible preventive methods and effective medical approach and long-term prognosis are required.


Asunto(s)
Colitis/terapia , Eosinofilia/terapia , Colitis/diagnóstico , Colitis/epidemiología , Colitis/etiología , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/epidemiología , Eosinofilia/etiología , Hipersensibilidad a los Alimentos/complicaciones , Humanos , Lactante , Pronóstico
5.
Can J Gastroenterol ; 25(1): 35-8, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21258666

RESUMEN

Proton pump inhibitors (PPIs) are the gold standard treatment for gastroesophageal reflux disease. In clinical practice, failure of PPIs occurs frequently, and may affect up to 30% of patients in a typical gastroenterology practice. Multichannel impedance monitoring combined with pH monitoring helps to detect nonacid reflux, and if symptoms correlate with these nonacid reflux episodes, nonacid reflux disease can be diagnosed. In contrast to PPIs, reflux inhibitors target transient lower esophageal sphincter relaxations, which are involved in the pathophysiology of reflux disease and may be the appropriate future treatment for nonacid reflux disease. The present article discusses the current understanding of nonacid reflux disease, its diagnosis and treatment.


Asunto(s)
Esfínter Esofágico Inferior/fisiopatología , Reflujo Gastroesofágico/fisiopatología , Baclofeno/análogos & derivados , Baclofeno/farmacología , Baclofeno/uso terapéutico , Esfínter Esofágico Inferior/efectos de los fármacos , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Ácidos Fosfínicos/farmacología , Ácidos Fosfínicos/uso terapéutico , Propilaminas/farmacología , Propilaminas/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Receptores de GABA-A/efectos de los fármacos
6.
Age Ageing ; 39(2): 162-8, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20065357

RESUMEN

Diarrhoeal diseases are common in older populations and often markedly affect their quality of life. Although there are numerous potential causes, microscopic colitis (MC) is increasingly recognised as a major diagnostic entity in older individuals. MC is comprised of two distinct histological forms - collagenous colitis and lymphocytic colitis, both of which frequently occur in older populations. Recent studies suggest that between 10 and 30% of older patients investigated for chronic diarrhoea with an endoscopically normal appearing colon will have MC. It is unclear why MC is more common in older populations, but it is associated with both autoimmune disorders and several drugs that are commonly used by seniors. A definitive diagnosis can only be made with colonic biopsies. Since MC was first described in 1976 and only recently recognised as a common cause of diarrhoea, many practising physicians may not be aware of this entity. In this review, we outline the epidemiology, risk factors associated with MC, its pathophysiology, the approach to diagnosis and the management of these individuals.


Asunto(s)
Antidiarreicos/uso terapéutico , Colitis Microscópica/complicaciones , Diarrea/etiología , Fármacos Gastrointestinales/uso terapéutico , Adulto , Biopsia , Enfermedad Crónica , Colitis Microscópica/epidemiología , Colitis Microscópica/patología , Colitis Microscópica/terapia , Colonoscopía , Diarrea/tratamiento farmacológico , Diarrea/patología , Humanos , Pronóstico , Factores de Riesgo , Factores Sexuales
7.
J Mol Med (Berl) ; 86(8): 925-36, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18493729

RESUMEN

The endocannabinoid (EC) system mediates protection against intestinal inflammation. In this study, we investigated the effects of blocking EC degradation or cellular reuptake in experimental colitis in mice. Mice were treated with trinitrobenzene-sulfonic acid in presence and absence of the fatty acid amide hydrolase (FAAH) blocker URB597, the EC membrane transport inhibitor VDM11, and combinations of both. Inflammation was significantly reduced in the presence of URB597, VDM11, or both as evaluated by macroscopic damage score, myeloperoxidase levels, and colon length. These effects were abolished in CB(1)- and CB(2)-receptor-gene-deficient mice. Quantitative reverse transcription polymerase chain reaction after induction of experimental colitis by different pathways showed that expression of FAAH messenger RNA (mRNA) is significantly reduced in different models of inflammation early in the expression of colitis, and these return to control levels as the disease progresses. Genomic DNA from 202 patients with Crohn's disease (CD) and 206 healthy controls was analyzed for the C385A polymorphism in the FAAH gene to address a possible role in humans. In our groups, the C385A polymorphism was equally distributed in patients with CD and healthy controls. In conclusion, drugs targeting EC degradation offer therapeutic potential in the treatment of inflammatory bowel diseases. Furthermore, reduction of FAAH mRNA expression is involved in the pathophysiological response to colitis.


Asunto(s)
Moduladores de Receptores de Cannabinoides/metabolismo , Colitis/tratamiento farmacológico , Endocannabinoides , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/metabolismo , Amidohidrolasas/antagonistas & inhibidores , Amidohidrolasas/genética , Amidohidrolasas/metabolismo , Animales , Ácidos Araquidónicos/uso terapéutico , Benzamidas/uso terapéutico , Carbamatos/uso terapéutico , Colitis/metabolismo , Enfermedad de Crohn/genética , Enfermedad de Crohn/metabolismo , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos C57BL , Polimorfismo Genético , ARN Mensajero/metabolismo , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB2/genética , Ácido Trinitrobencenosulfónico/uso terapéutico
8.
Curr Opin Pharmacol ; 7(6): 575-82, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17904903

RESUMEN

The endocannabinoid system (ECS) consists of cannabinoid receptors, endogenous ligands and the biosynthetic and metabolic enzymes for their formation and degradation. Within the gastrointestinal (GI) tract, the ECS is involved in the regulation of motility, secretion, sensation, emesis, satiety and inflammation. Recent studies examining the ECS in the gut-brain axis have shed new light on this system and reveal many facets of regulation that are amenable to targeting by pharmacological interventions that may prove valuable for the treatment of GI disorders. In particular, it has been shown that endocannabinoid levels in the brain and gut vary according to states of satiety, and in conditions of diarrhea, emesis and inflammation. The expression of cannabinoid (CB)(1) receptors on vagal afferents is controlled by the states of satiety and by gut peptides such as cholecystokinin and ghrelin. Vagal control of gut motor function and emesis is regulated by endocannabinoids in the brainstem acting on CB(1), CB(2) and transient receptor potential vanilloid (TRPV)-1 receptors. The ECS is involved in the modulation of visceral sensation and likely contributes to effects of stress on GI function. This review examines recent developments in our understanding of the ECS in gut-brain signalling.


Asunto(s)
Encéfalo/fisiología , Moduladores de Receptores de Cannabinoides/fisiología , Endocannabinoides , Tracto Gastrointestinal/fisiología , Transducción de Señal/fisiología , Animales , Química Encefálica , Moduladores de Receptores de Cannabinoides/metabolismo , Tracto Gastrointestinal/metabolismo , Humanos , Receptor Cannabinoide CB1/fisiología , Receptor Cannabinoide CB2/fisiología , Canales Catiónicos TRPV/fisiología
9.
United European Gastroenterol J ; 5(3): 335-358, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28507746

RESUMEN

INTRODUCTION: Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. METHODS: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. RESULTS: The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. CONCLUSION: Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.

10.
J Inflamm (Lond) ; 13: 21, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27418880

RESUMEN

BACKGROUND: Non-psychotropic atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions including those of the gastrointestinal tract. Here we examined the effects of the atypical cannabinoid abnormal cannabidiol (Abn-CBD) on wound healing, inflammatory cell recruitment and colitis in mice. METHODS: Colitis was induced in CD1 mice by a single intrarectal administration of trinitrobenzene sulfonic acid (TNBS, 4 mg/100 µl in 30 % ethanol) and Abn-CBD and/or the antagonists O-1918 (Abd-CBD), AM251 (CB1 receptor) and AM630 (CB2 receptor), were administered intraperitoneally (all 5 mg/kg, twice daily for 3 days). The degree of colitis was assessed macro- and microscopically and tissue myeloperoxidase activity was determined. The effects of Abn-CBD on wound healing of endothelial and epithelial cells (LoVo) were assessed in a scratch injury assay. Human neutrophils were employed in Transwell assays or perfused over human umbilical vein endothelial cells (HUVEC) to study the effect of Abn-CBD on neutrophil accumulation and transmigration. RESULTS: TNBS-induced colitis was attenuated by treatment with Abn-CBD. Histological, macroscopic colitis scores and tissue myeloperoxidase activity were significantly reduced. These effects were inhibited by O-1918, but not by AM630, and only in part by AM251. Wound healing of both HUVEC and LoVo cells was enhanced by Abn-CBD. Abn-CBD inhibited neutrophil migration towards IL-8, and dose-dependently inhibited accumulation of neutrophils on HUVEC. CONCLUSIONS: Abn-CBD is protective against TNBS-induced colitis, promotes wound healing of endothelial and epithelial cells and inhibits neutrophil accumulation on HUVEC monolayers. Thus, the atypical cannabinoid Abn-CBD represents a novel potential therapeutic in the treatment of intestinal inflammatory diseases.

11.
J Gastroenterol ; 49(1): 24-45, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23397116

RESUMEN

Opioid receptors are widely distributed in the human body and are crucially involved in numerous physiological processes. These include pain signaling in the central and the peripheral nervous system, reproduction, growth, respiration, and immunological response. Opioid receptors additionally play a major role in the gastrointestinal (GI) tract in physiological and pathophysiological conditions. This review discusses the physiology and pharmacology of the opioid system in the GI tract. We additionally focus on GI disorders and malfunctions, where pathophysiology involves the endogenous opioid system, such as opioid-induced bowel dysfunction, opioid-induced constipation or abdominal pain. Based on recent reports in the field of pharmacology and medicinal chemistry, we will also discuss the opportunities of targeting the opioid system, suggesting future treatment options for functional disorders and inflammatory states of the GI tract.


Asunto(s)
Enfermedades Gastrointestinales/fisiopatología , Receptores Opioides/fisiología , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Gastrointestinales/tratamiento farmacológico , Tracto Gastrointestinal/metabolismo , Humanos , Ligandos , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/tendencias , Antagonistas de Narcóticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Transducción de Señal/fisiología
12.
Can J Gastroenterol Hepatol ; 28(6): 335-41, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24719900

RESUMEN

Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy.


Asunto(s)
Árboles de Decisión , Reflujo Gastroesofágico/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Monitorización del pH Esofágico , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/patología , Pirosis/diagnóstico , Pirosis/tratamiento farmacológico , Pirosis/patología , Humanos , Índice de Severidad de la Enfermedad , Insuficiencia del Tratamiento
13.
Nat Commun ; 4: 1630, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23535651

RESUMEN

The enteric nervous system contains excitatory and inhibitory neurons, which control contraction and relaxation of smooth muscle cells as well as gastrointestinal motor activity. Little is known about the exact cellular mechanisms of neuronal signal transduction to smooth muscle cells in the gut. Here we generate a c-Kit(CreERT2) knock-in allele to target a distinct population of pacemaker cells called interstitial cells of Cajal. By genetic loss-of-function studies, we show that interstitial cells of Cajal, which generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature, are essential for transmission of signals from enteric neurons to gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore, integrate excitatory and inhibitory neurotransmission with slow-wave activity to orchestrate peristaltic motor activity of the gut. Impairment of the function of interstitial cells of Cajal causes severe gastrointestinal motor disorders. The results of our study show at the genetic level that these disorders are not only due to loss of slow-wave activity but also due to disturbed neurotransmission.


Asunto(s)
Sistema Nervioso Entérico/fisiología , Células Intersticiales de Cajal/fisiología , Transmisión Sináptica , Animales , Células Cultivadas , Proteína Quinasa Dependiente de GMP Cíclico Tipo I/genética , Ratones , Ratones Transgénicos
14.
PLoS One ; 8(12): e85073, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24386448

RESUMEN

AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS) was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients. METHODS: AEA, 2-AG, OEA and PEA plasma levels were determined in diarrhoea-predominant (IBS-D) and constipation-predominant (IBS-C) patients and were compared to healthy subjects, following the establishment of correlations between biolipid contents and disease symptoms. FAAH mRNA levels were evaluated in colonic biopsies from IBS-D and IBS-C patients and matched controls. RESULTS: Patients with IBS-D had higher levels of 2AG and lower levels of OEA and PEA. In contrast, patients with IBS-C had higher levels of OEA. Multivariate analysis found that lower PEA levels are associated with cramping abdominal pain. FAAH mRNA levels were lower in patients with IBS-C. CONCLUSION: IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.


Asunto(s)
Amidas/sangre , Endocannabinoides/sangre , Ácidos Grasos/sangre , Síndrome del Colon Irritable/sangre , Adulto , Estreñimiento/sangre , Diarrea/sangre , Femenino , Humanos
15.
Front Pharmacol ; 3: 127, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22783191

RESUMEN

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with an estimated prevalence of 10-20%. Current understanding of the pathophysiology of IBS is incomplete due to the lack of a clearly identified pathological abnormality and due to the lack of reliable biomarkers. Possible mechanisms believed to contribute to IBS development and IBS like symptoms include physical stressors, such as infection or inflammation, psychological, and environmental factors, like anxiety, depression, and significant negative life events. Some of these mechanisms may involve the brain-gut axis (BGA). In this article we review the current knowledge on the possible involvement of the BGA in IBS and discuss new directions for potential future therapies of IBS.

16.
Inflamm Bowel Dis ; 18(6): 1137-45, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21953882

RESUMEN

BACKGROUND: Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice. METHODS: Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). RESULTS: The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls. CONCLUSIONS: Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases.


Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Colitis/tratamiento farmacológico , Diterpenos de Tipo Clerodano/uso terapéutico , Motilidad Gastrointestinal/efectos de los fármacos , Dolor/tratamiento farmacológico , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/metabolismo , Receptores Opioides kappa/metabolismo , Animales , Western Blotting , Colitis/inducido químicamente , Colitis/metabolismo , Colon/efectos de los fármacos , Colon/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Masculino , Ratones , Naltrexona/análogos & derivados , Dolor/metabolismo , Peroxidasa , Salvia/química , Ácido Trinitrobencenosulfónico/toxicidad
17.
Pharmacol Rep ; 64(5): 1146-54, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23238471

RESUMEN

BACKGROUND: Animal models of visceral pain have gained much attention as an important tool to elucidate the possible mechanisms underlying functional gastrointestinal (GI) disorders. Here we report the development of a new, minimally invasive behavioral model of abdominal pain induced by ip administration of neostigmine in mice. METHODS: Spontaneous behavioral responses evoked by ip injection of neostigmine were compared to pain-related behaviors induced by acetic acid solution (ip), mustard oil (MO) and capsaicin (both ic). Pain behaviors were quantified by assessment of defined postures (licking of the abdomen, stretching, squashing of the abdomen and abdominal contractions). Neuronal activation of spinal cord was measured by determining the number of c-Fos-positive cells. RESULTS: Neostigmine (2.5 µg/kg, ip), acetic acid solution (ip), MO and capsaicin (both ic) induced spontaneous behavioral responses in mice, which were blocked by morphine (3 mg/kg, ip), suggesting the involvement of pain signaling pathways. Injection of neostigmine enhanced c-Fos expression in spinal cord neurons. CONCLUSION: The neostigmine model represents a new minimally invasive mouse model to study visceral pain. Based on the neuronal activation pattern in the spinal cord we suggest that this model may be used to study abdominal pain signaling pathways in the GI tract.


Asunto(s)
Dolor Abdominal/etiología , Modelos Animales de Enfermedad , Neostigmina/farmacología , Dolor Abdominal/tratamiento farmacológico , Dolor Abdominal/psicología , Animales , Masculino , Ratones , Morfina/uso terapéutico , Proteínas Proto-Oncogénicas c-fos/análisis , Transducción de Señal
18.
Therap Adv Gastroenterol ; 4(5): 301-9, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21922029

RESUMEN

Primary eosinophilic gastrointestinal disorders (EGIDs) represent a spectrum of inflammatory gastrointestinal disorders in which eosinophils infiltrate the gut in the absence of known causes for such tissue eosinophilia. EGIDs can be subgrouped as eosinophilic esophagitis (EE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC). The least frequent manifestation of EGIDs is EC. EC is a heterogeneous entity with a bimodal age distribution, presenting with either an acute self-limited bloody diarrhea in otherwise healthy infants or as a more chronic relapsing colitis in young adults. The pathophysiology of primary EC appears related to altered hypersensitivity, principally as a food allergy in infants and T lymphocyte-mediated (i.e. non-IgE associated) in young adults. In adults, symptoms include diarrhea, abdominal pain, and weight loss. Endoscopic changes are generally modest, featuring edema and patchy granularity. Although standardized criteria are not yet established, the diagnosis of EC depends on histopathology that identifies an excess of eosinophils. Therapeutic approaches are based on case reports and small case series, as prospective randomized controlled trials are lacking. Eosinophilic colitis in infants is a rather benign, frequently food-related entity and dietary elimination of the aggressor often resolves the disorder within days. Adolescent or older patients require more aggressive medical management including: glucocorticoids, anti-histamines, leukotriene receptors antagonists as well as novel approaches employing biologics that target interleukin-5 (IL-5) and IgE. This review article summarizes the current knowledge of EC, its epidemiology, clinical manifestations, diagnosis, and treatment.

19.
Nat Rev Gastroenterol Hepatol ; 7(10): 583-8, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20808292

RESUMEN

BACKGROUND: A 38-year-old female presented with a 3-year history of postprandial abdominal pain, refractory nausea, vomiting and hematemesis. She appeared malnourished and her symptoms were refractory to previous treatment with acid-suppressive drugs, prokinetics and antiemetics. Her medical history was significant for a diagnosis of juvenile polyposis syndrome at the age of 14 resulting in a transverse colectomy, and a diagnosis of Crohn's disease in her residual colon at the age of 35 resulting in a total colectomy. INVESTIGATIONS: Physical examination, blood analysis, esophagogastroduodenoscopy with biopsy, abdominal endoscopic ultrasound, abdominal CT scan, MRI, 24 h urine analysis, MIBG scintigraphy, ocreotide scintigraphy, fluorodeoxyglucose-PET scan and genetic testing for defined polyposis syndromes (SMAD4, BMPR1A). DIAGNOSIS: Juvenile polyposis syndrome with outlet obstruction of the stomach and excessive hypergastrinemia. MANAGEMENT: Continuous acid-suppressive therapy, prokinetic therapy and total parenteral nutrition. Repetitive endoscopic polypectomy (also known as debulking) was performed twice and was followed by gastrectomy with duodenoesophageal anastomosis.


Asunto(s)
Obstrucción de la Salida Gástrica/complicaciones , Gastrinas/sangre , Adulto , Antiácidos , Endoscopía del Sistema Digestivo , Femenino , Gastrectomía , Obstrucción de la Salida Gástrica/diagnóstico , Humanos , Poliposis Intestinal/complicaciones , Poliposis Intestinal/congénito , Poliposis Intestinal/diagnóstico , Síndromes Neoplásicos Hereditarios , Nutrición Parenteral
20.
Chem Biol Drug Des ; 76(1): 77-81, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20456368

RESUMEN

The endogenous opioid system is involved in the control of gastrointestinal (GI) motility. The potential use of endogenous MOR ligands, endomorphins (EMs), as therapeutics is limited because of their rapid enzymatic degradation and short duration of action. Targeting enzymatic degradation is an approach to prolong EM activity. In the present study, we characterized the effects of novel blockers of EM degradation in GI tissue preparation in vitro. The effects of actinonin, diprotin A (DIP) and the novel peptide EM degradation blockers Tyr-Pro-DClPhe-Phe-NH(2) (EMDB-1), Tyr-Pro-Ala-NH(2) (EMDB-2) and Tyr-Pro-Ala-OH (EMDB-3) on EM-2-mediated inhibition of electrically induced cholinergic twitch contractions were compared in rat ileum in vitro using an organ bath. EMDB-1 and EMDB-2 significantly prolonged the inhibitory effect of EM-2 on smooth muscle contractility in rat ileum. EMDB-2 extended the EM-2 action for up to 60 min compared to 10 min in controls and was more potent than the conventional peptidase inhibitor DIP. EMDB-1 and EMDB-2 are potent EM degradation blockers, which prolong the inhibitory effects of EM-2 on smooth muscle contractility in rat ileum. These novel compounds may be of future use when targeting the endogenous opioid system in the treatment of GI motility disorders such as diarrhea.


Asunto(s)
Íleon/efectos de los fármacos , Oligopéptidos/farmacología , Secuencia de Aminoácidos , Animales , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Íleon/metabolismo , Oligopéptidos/química , Oligopéptidos/metabolismo , Ratas
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