Effects of maternal hypothyroidism in the gastrointestinal system of male young offspring from Wistar rats.

Alterations in the maternal environment may impact on the fetal development. The objective of this study was to investigate the gastrointestinal consequences of maternal hypothyroidism for the male offspring from Wistar rats. The pregnant rats were divided into three groups: control (C - received water), experimental 1 [E1 - received methimazole (MMI) solution] during gestation and lactation, and experimental 2 (E2 - received MMI solution) during gestation. Maternal parameters evaluated: free T3 and T4, bodyweight variation, and water/food intake. Offspring parameters evaluated: litter size, number of male/female, free T3 and T4, stomach area, gastric ulcer susceptibility, small intestine length and weight, small intestine and distal colon motility, the stomach and intestinal weight-body weight ratio (SW/BW-IW/BW), and the accumulation of intestinal fluid. Maternal T3 and T4 from E1 were decreased when compared to the other groups. There were no differences for maternal water/food intake and weight gain, litter size, and number of males and females. Regarding to offspring, free T3, SW/BW, IW/BW, and intestinal fluid accumulation were not different between the groups, but T4 was decreased in E1. However, 30-day-old pups from E1 and E2 were smaller with lower stomach and small intestine. Even more, E1 presented a lower ulcer index when compared to the C, while E2 had a higher distal colon transit. It can be concluded that maternal hypothyroidism impaired the total body development, as well as gastric and intestinal development, besides interfering with the susceptibility to the ulcer and intestinal transit of male offspring from Wistar rats.

Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease.

BACKGROUND: Although empiric exclusion from the diet of the 6 food groups most likely to trigger allergies achieves eosinophilic esophagitis (EoE) remission in children, data on its prolonged efficacy and effects on adults are lacking. OBJECTIVE: We sought to evaluate the efficacy of a 6-food elimination diet in inducing and maintaining prolonged remission in patients with adult EoE. METHODS: Sixty-seven consecutive patients with adult EoE were prospectively recruited and treated exclusively with a diet avoiding cereals, milk, eggs, fish/seafood, legumes/peanuts, and soy for 6 weeks. Subsequent challenge was undertaken by sequentially reintroducing all excluded single foods, followed by endoscopy and biopsies, which were developed every 6 weeks in case of response (eosinophil peak count reduction to <15/high-power field [hpf]). A food was considered a trigger for EoE and removed from the diet if pathologic eosinophilic infiltration (≥15 eosinophils/hpf) reappeared. Food-specific serum IgE measurements and skin prick tests were performed before initiating the diet. RESULTS: Forty-nine (73.1%) patients exhibited significantly reduced eosinophil peak counts (<15 eosinophils/hpf) before sequential single-food reintroduction. A single offending food antigen was identified in 35.71% of patients, 2 food triggers were identified in 30.95%, and 3 or more food triggers were identified in 33.3%. Cow's milk was the most common food antigen (61.9%), followed by wheat (28.6%), eggs (26.2%), and legumes (23.8%). Prior allergy tests showed no concordance with food-reintroduction challenge results. All patients who continued to avoid the offending foods maintained histopathologic and clinical EoE remission for up to 3 years. CONCLUSIONS: An empiric 6-food elimination diet effectively induced remission of active adult EoE, which was maintained for up to 3 years with individually tailored, limited exclusion diets.

Subepithelial collagen deposition, profibrogenic cytokine gene expression, and changes after prolonged fluticasone propionate treatment in adult eosinophilic esophagitis: a prospective study.

BACKGROUND: Recent research shows that both pediatric and adult patients with eosinophilic esophagitis (EoE) experience esophageal remodeling marked by increased collagen deposition in which TGF-ß plays an important role. However, limited data are available on the intensity and reversibility of fibrous remodeling in adults with EoE. OBJECTIVE: We sought to analyze differences in collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene expression along with other changes induced by prolonged treatment with fluticasone propionate in adults with EoE. METHODS: Ten adults given consecutive diagnoses of EoE were studied prospectively. Deep esophageal biopsy specimens were obtained before and after 1 year of treatment with fluticasone propionate. Collagen deposition in the LP was assessed in tissue sections with the aid of the Masson trichrome technique. IL5, TGFB1, fibroblast growth factor 9 (FGF9), and CCL18 gene expression was quantified through real-time PCR. EoE results were compared among samples from 10 adult patients with gastroesophageal reflux disease and 10 control subjects with healthy esophagi. RESULTS: Patients with EoE showed a significant increase in subepithelial collagen deposition; this correlated positively with eosinophil density in the LP and the patient's age. Prolonged steroid treatment induced a nonsignificant reduction in subepithelial fibrosis, which remained significantly higher than in control subjects. Profibrogenic cytokine gene expression also increased in patients with EoE, with IL5 (P < .001), FGF9 (P = .005), and CCL18 (P = .008) all significantly upregulated. After 1 year of treatment, a reduction was observed in gene expression; for CCL18 expression, this decrease was statistically significant (P < .001). CONCLUSIONS: Esophageal remodeling is associated with upregulated gene expression of profibrogenic cytokines in adults with EoE. Prolonged treatment with fluticasone propionate leads to a nonsignificant reduction in subepithelial collagen deposition accompanied by downregulation of profibrogenic cytokine gene expression, with that of CCL18 being especially significant.

Montelukast was inefficient in maintaining steroid-induced remission in adult eosinophilic esophagitis.

BACKGROUND AND AIMS: Leukotriene D4 is produced by and functions as a chemotactic factor for eosinophils. Eosinophilic esophagitis (EoE) is characterized by esophageal eosinophilic infiltration, determining structural changes and dismotility symptoms. Montelukast, a selective leukotriene D4 receptor antagonist, has gained increasing consideration as a therapeutic agent for EoE. However, limited available information has shown that montelukast is not effective in reducing eosinophilic infiltration. Our paper aims at evaluating whether montelukast could be consider as a steroid-sparing therapy by assessing its efficacy in maintaining both clinical and histopathological remission achieved after topical corticosteroids in adult EoE patients. METHODS: Eleven consecutively diagnosed adult EoE patients were prospectively studied. Esophageal biopsies were obtained before and after a 6-month treatment with fluticasone propionate 400 µg/twice a day. Immediately after that, montelukast 10 mg/day was instituted. A new endoscopy was foreseen after a new 3-month period, or as soon as the patients presented esophageal symptoms. Symptoms were assessed by using a questionnaire before and after fluticasone propionate treatment and after montelukast therapy. RESULTS: Eosinophils density into the esophageal epithelium and lamina propria was significantly reduced after a 6-month treatment with topical steroids (P = 0.003) and increased to levels similar to baseline level into the first 3 months after treatment with montelukast. Baseline symptom scores significantly decreased after treatment with topical steroids (P = 0.003) and increased again after montelukast therapy, but baseline levels improved. CONCLUSIONS: Montelukast was not efficient in maintaining the histopathological or clinical response achieved by topical steroids in adult EoE patients.

Adult patients with eosinophilic esophagitis do not show an increased frequency of the HLA-DQ2/DQ8 genotypes predisposing to celiac disease.

BACKGROUND: Recent articles have described patients that share eosinophilic esophagitis (EoE) and celiac disease (CD) suggesting a true relationship between both diseases. AIMS: The purpose of this study was to investigate whether HLA DQ2 and DQ8 predisposing to CD are increased in adult patients with EoE. METHODS: HLA alleles conferring risk for CD was assessed in 75 adult EoE patients attended at two hospitals located in different Spanish regions over the past 2 years. We compared the frequencies to the registered data of 421 healthy kidney and bone marrow donors from our hospitals for the following alleles: (a) DR3-DQ2 haplotype; (b) the combination of DR3-DQ2 and DR4-DQ8; (c) DR4-DQ8 haplotype; (d) the simultaneous presence of the DR5-DQ7 and DR7-DQ2 haplotypes; and lastly (e) any combination of haplotypes not conferring risk for the development of CD. RESULTS: The HLA DQ2 and DQ8 alleles were analyzed in 58 adult EoE patients from hospital #1 and in 20 patients from hospital #2, and they were compared to recorded HLA genotyping data from 298 and 123 healthy donors, respectively. No differences were found between the distribution of the HLA frequencies of the patients and controls at both hospitals and the data could be combined. EoE patients did not show increased frequencies of DQ2 and DQ8 alleles compared to controls. CONCLUSIONS: Our work does not allow us to establish a common genetic basis for EoE and CD because an increased frequency of the HLA DQ2 and DQ8 alleles predisposing to CD was not observed in adult EoE patients compared to controls.

Importance of nutrition in inflammatory bowel disease.

Inflammatory bowel disease (IBD) results from the interaction between an individual's immune response and precipitant environmental factors, which generate an anomalous chronic inflammatory response in those who are genetically predisposed. Various feeding practices have been implicated in the origin of IBD based on epidemiological observations in developed countries, but we do not have solid evidence for the etiological role played by specific food types. IBD is associated with frequent nutritional deficiencies, the pattern and severity of which depends on the extent, duration and activity of the inflammation. Nutritional support allows these deficiencies in calories, macro- and micro-nutrients to be rectified. Enteral nutrition is also a primary therapy for IBD, especially for Crohn's disease, as it allows the inflammatory activity to be controlled, kept in remission, and prevents or delays the need for surgery. Nutritional support is especially important in childhood IBD as an alternative to pharmacological treatment. This report discusses the complex relationship between diet and IBD.

Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis.

OBJECTIVES: Our aim was to evaluate the changes induced by topical steroid treatment to the esophageal epithelial inflammatory eosinophilic and T-cell infiltrate and to IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 esophageal gene expression levels in patients with eosinophilic esophagitis (EE). METHODS: Esophageal biopsies were taken from eight adult patients at the moment of diagnosis and after 3-month treatment with fluticasone propionate. Eosinophils, CD8, and CD4 T cells were examined by immunohistochemistry. IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression levels were measured by real-time PCR. Eight control samples were also analyzed. RESULTS: A significant decrease in the eosinophil infiltrate and in CD8(+) T-cell density was observed in the esophageal epithelium from the patients upon steroid treatment. IL-5 was not detected in control samples, and expression levels were variably downregulated after treatment in six of the patients. Gene expression of eotaxin-1/CCL11 showed relevant downregulation in four cases and a modest twofold decrease in three of the patients studied. Mean CCL11 expression values upon steroid treatment were similar to control samples (19.4 +/- 28.6 vs 8.42 +/- 5, P= 0.7). Eotaxin-3/CCL26 gene expression levels were significantly increased in EE. Although they were significantly downregulated upon steroid treatment, control expression levels were not reached in any of the cases analyzed (580.9 +/- 943.9 vs 1.45 +/- 1.0, P= 0.001). CONCLUSIONS: Our results confirm that eotaxin-3/CCL26 is significantly increased in EE esophageal samples. However, the individual analysis of IL-5, CCL11, and CCL26 expression data suggests that several cytokines and chemokines could participate in the physiopathology of EE in humans.

Esophageal granular cell tumor and eosinophilic esophagitis: two interesting entities identified in the same patient.

We illustrate the case of a 41-year-old male with allergic manifestations since childhood. He sought medical attention for intermittent, progressive dysphagia from which he had been suffering for a number of years, having felt the sensation of a retrosternal lump and a self-limited obstruction to the passage of food. Endoscopy detected a submucosal tumor in the upper third of the esophagus, which was typified, via biopsy, as a granular cell tumor with benign characteristics and probably responsible for the symptoms. Two years later, the patient sought medical attention once again as these symptoms had not abated, hence digestive endoscopy was repeated. This revealed stenosis of the junction between the middle and lower thirds of the organ which had not been detected previously but was passable under gentle pressure. Eosinophilic esophagitis was detected after biopsies were taken. Esophageal manometry identified a motor disorder affecting the esophageal body. Following three months of treatment using fluticasone propionate applied topically, the symptoms went into remission, esophageal stenosis disappeared and the esophageal biopsies returned to normal. This is the first documented case of the link between granular cell tumors and Eosinophilic esophagitis, two different disorders which could cause dysphagia in young patients.

[Eosinophilic esophagitis. Review of current clinical and physiopathological concepts]. / Esofagitis eosinofílica. Revisión de los conceptos fisiopatológicos y clínicos actuales.

Eosinophilc esophagitis (EE) is an emerging disease which is characterized by a dense infiltration of the esophagus by eosinophilic leukocytes. The main symptoms of this disease are dysphagia and frequent food impaction in esophagus, and they are due to a hypersentivity response to different foods or aeroallergens. Eosinophil accumulation in the esophageal epithelium is determined by local production of eosinophilotropic cytokines and chemokines, which have been well defined as a TH2-type hypersensitivity reaction in animal models of the disease. Esophageal epithelium, after T CD4+ lymphocytes stimulation, contains all the necessary cell types for the development of local immunoallergic responses. However, there is increasing data on the significant role that humoral immunity could play in the pathophysiology of EE, by means of the action of IgE over mast cells function. The high density of T CD8+ lymphocytes in inflammatory infiltrate suggests that a TH1-type reaction could also participate in the mechanism of the disease. Proteins contained in cytoplasmic granules of activated eosinophils and mast cells could act over neural and muscular components of the esophageal wall, triggering motor disturbances which can be measured by means of manometric recordings and justify the esophageal symptoms. This paper aims to review the newest clinical aspects of EE and the results of studies directed at investigating the pathophysiology of the disease. Furthermore, we carry out a critical review of available therapeutic options.