Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis

Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described. We now report a system with such hallmarks. Specifically, we identify endocannabinoids as the first known endogenous substrates of the apically restricted multidrug resistance transporter P-glycoprotein (P-gp) and reveal a mechanism, which we believe is novel, for endocannabinoid secretion into the intestinal lumen. Knockdown or inhibition of P-gp reduced luminal secretion levels of N-acyl ethanolamine-type endocannabinoids, which correlated with increased neutrophil transmigration in vitro and in vivo. Additionally, loss of CB2, the peripheral cannabinoid receptor, led to increased pathology and neutrophil influx in models of acute intestinal inflammation. These results define a key role for epithelial cells in balancing the constitutive secretion of antiinflammatory lipids with the stimulated secretion of proinflammatory lipids via surface efflux pumps in order to control neutrophil infiltration into the intestinal lumen and maintain homeostasis in the healthy intestine

Utility of Diagnostic Tests in Children With Functional Abdominal Pain Disorders

Functional gastrointestinal disorders (FGIDs) and functional abdominal pain disorders (FAPDs) are common in pediatric patients. The prevalence of FGIDs using the Rome IV criteria ranges from 21.1% to 25.0% in children. The Rome IV criteria specify that the decision of testing is left to the clinician, giving him or her freedom to decide on the necessary workup. The clinician should consider all of the functional and organic diseases that manifest with chronic abdominal pain, as well as alarm features that should prompt testing. Societal guidelines and reports do not recommend routine evaluations for FAPDs, particularly in the absence of alarm features. Studies have reported variable results upon assessing the diagnostic yields of different tests. Furthermore, these evaluations considerably increase costs for the health care system. This article examines the current evidence on the utility of diagnostic testing in pediatric patients with FAPDs

Gluten and Functional Abdominal Pain Disorders in Children

In children, functional gastrointestinal disorders (FGIDs) are common at all ages. Consumption of certain foods, particularly gluten, is frequently associated with the development and persistence of FGIDs and functional abdominal pain disorders (FAPDs) in adults and children. However, this association is not well defined. Even without a diagnosis of celiac disease (CD), some people avoid gluten or wheat in their diet since it has been shown to trigger mostly gastrointestinal symptoms in certain individuals, especially in children. The incidence of conditions such as non-celiac gluten sensitivity (NCGS) is increasing, particularly in children. On the other hand, CD is a chronic, autoimmune small intestinal enteropathy with symptoms that can sometimes be mimicked by FAPD. It is still unclear if pediatric patients with irritable bowel syndrome (IBS) are more likely to have CD. Abdominal, pain-associated FGID in children with CD does not seem to improve on a gluten-free diet. The threshold for gluten tolerance in patients with NCGS is unknown and varies among subjects. Thus, it is challenging to clearly distinguish between gluten exclusion and improvement of symptoms related solely to functional disorders

Utility of the Brussels Infant and Toddler Stool Scale (BITSS) and Bristol Stool Scale in non-toilet-trained children: A large comparative study

BACKGROUNDOne of the criteria for functional constipation (FC) in Rome IV criteria is the presence of hard or painful bowel movements. In adults and children, the Rome IV criteria recommend the use of the Bristol Stool Scale (BSS). This scale is thought not to be appropriate for evaluation of stool consistency in young children. The Brussels Infant and Toddler Stool Scale (BITSS) was developed as a scale for children wearing diapers. There are no prior studies comparing BITSS with BSS in a clinical setting. Our main aim was that BITSS behaves differently than the BSS as it reflects better stool characterization by parents. METHODSSurveys were provided to parents of participants in two cities from Colombia which included the Rome IV-validated questionnaire and stool consistency assessment using pictures for BSS and BITSS. KEY RESULTSA total of 666 responses were obtained for non-toilet-trained children, mean age was 16.6 months. Detection for normal stools was higher using BSS (58.6%) when compared to BITSS (13.6%), and conversely was more likely to be abnormal through BITSS (86.4%) than BSS (41.4%) (p < 0.0001). BITSS (57.4%) was better than BSS (25.3%) identifying hard stools in FC (p = 0.000). For hard stools per parental classification, BITSS' definition was better than BSS (75.8% vs 44%, respectively, p = 0.000). CONCLUSIONSThe BITSS and BSS behave differently. The BITSS seems to be more sensitive to detect hard stools and FC than BSS. More studies are needed to better define whether BITSS is appropriate to replace BSS in non-toilet-trained infants and toddlers

Characteristics of Travel-Related Severe Plasmodium vivax and Plasmodium falciparum Malaria in Individuals Hospitalized at a Tertiary Referral Center in Lima, Peru.

Severe Plasmodium falciparum malaria is uncommon in South America. Lima, Peru, while not endemic for malaria, is home to specialized centers for infectious diseases that admit and manage patients with severe malaria (SM), all of whom contracted infection during travel. This retrospective study describes severe travel-related malaria in individuals admitted to one tertiary care referral hospital in Lima, Peru; severity was classified based on criteria published by the World Health Organization in 2000. Data were abstracted from medical records of patients with SM admitted to Hospital Nacional Cayetano Heredia from 2006 to 2011. Of 33 SM cases with complete clinical data, the mean age was 39 years and the male/female ratio was 2.8. Most cases were contracted in known endemic regions within Peru: Amazonia (47%), the central jungle (18%), and the northern coast (12%); cases were also found in five (15%) travelers returning from Africa. Plasmodium vivax was most commonly identified (71%) among the severe infections, followed by P. falciparum (18%); mixed infections composed 11% of the group. Among the criteria of severity, jaundice was most common (58%), followed by severe thrombocytopenia (47%), hyperpyrexia (32%), and shock (15%). Plasmodium vivax mono-infection predominated as the etiology of SM in cases acquired in Peru

Recurrent Severe Iron Deficiency Anemia and Thrombocytopenia in an Adolescent Male

An adolescent male presented with recurrent episodes over several years of severe iron deficiency anemia and associated severe thrombocytopenia. The anemia was secondary to chronic blood loss due to ulceration at the site of an ileocolonic anastomosis performed during infancy. We were able to demonstrate complete resolution of thrombocytopenia with the administration of iron, and without using steroids, intravenous immunoglobulin, or platelet transfusions. This is the first reported case of an individual with multiple episodes over several years of thrombocytopenia secondary to recurrent severe iron deficiency anemia, illustrating a predisposition to this complication in a unique patient

Novel Mutation in the SLC5A1 Gene Causing Glucose-Galactose Malabsorption: First Confirmed Case From Central America

Congenital glucose-galactose malabsorption is a rare cause of life-threatening diet-induced diarrhea in infants. Mutations in the SLC5A1 gene, which encodes for the sodium-dependent glucose transporter, result in large-volume diarrhea due to aberrant glucose and galactose transport across the intestinal brush border. The diagnosis can be made clinically based on the presence of diarrhea soon after birth, evidence of carbohydrate malabsorption in the stool, and resolution of diarrhea with dietary elimination of glucose and galactose. Genetic testing can confirm the diagnosis. Here we report the first confirmed case of glucose-galactose malabsorption in an infant from Central America due to a novel mutation in the SLC5A1 gene. The patient began growing and thriving after being diagnosed and with the correct dietary interventions