Prevalence of migraine in patients with celiac disease and inflammatory bowel disease.

OBJECTIVE: To assess the prevalence of headache in clinic and support group patients with celiac disease and inflammatory bowel disease (IBD) compared with a sample of healthy controls. BACKGROUND: European studies have demonstrated increased prevalence of headache of patients with celiac disease compared with controls. METHODS: Subjects took a self-administered survey containing clinical, demographic, and dietary data, as well as questions about headache type and frequency. The ID-Migraine screening tool and the Headache Impact Test (HIT-6) were also used. RESULTS: Five hundred and two subjects who met exclusion criteria were analyzed - 188 with celiac disease, 111 with IBD, 25 with gluten sensitivity (GS), and 178 controls (C). Chronic headaches were reported by 30% of celiac disease, 56% of GS, 23% of IBD, and 14% of control subjects (P<.0001). On multivariate logistic regression, celiac disease (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.78-8.10), GS (OR 9.53, 95%CI 3.24-28.09), and IBD (OR 2.66, 95%CI 1.08-6.54) subjects all had significantly higher prevalence of migraine headaches compared with controls. Female sex (P=.01), depression, and anxiety (P=.0059) were independent predictors of migraine headaches, whereas age >65 was protective (P=.0345). Seventy-two percent of celiac disease subjects graded their migraine as severe in impact, compared with 30% of IBD, 60% of GS, and 50% of C subjects (P=.0919). There was no correlation between years on gluten-free diet and migraine severity. CONCLUSIONS: Migraine was more prevalent in celiac disease and IBD subjects than in controls. Future studies should include screening migraine patients for celiac disease and assessing the effects of gluten-free diet on migraines in celiac disease.

Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice.

BACKGROUND: Cigarette smoking alters the course of inflammatory bowel disease, is associated with protection against ulcerative colitis, but aggravates or has no effect on Crohn's disease. While the aetiology of this discrepancy remains unclear, differences between location of involvement in ulcerative colitis and Crohn's disease have not been examined in these studies. AIM: To examine the effects of nicotine administration on the course of jejunitis and colitis in interleukin-10 deficient mice. METHODS: Male C57/BL10 IL-10 -/- and wild type mice were given nicotine (12.5 microg/ml) in their drinking water at age 12-14 weeks when they had developed clinical signs of inflammatory bowel disease. Gender and age matched control mice received tap water alone. All mice were killed after 2 weeks of treatment. Whole tissue sections of jejunum, proximal and distal colon were separated and examined by macroscopic and histological score. Northern blots were examined for somatostatin, intestinal trefoil factor and mucin-2. RESULTS: At 14-16 weeks, when the mice were killed, IL-10 -/- untreated control mice developed jejunitis (macroscopic score 1.4 +/- 0.5, microscopic score 2.0 +/- 0.2) and colitis (2.0 +/- 0.2 and 5.9 +/- 0.9, respectively). IL-10 -/- mice treated for 2 weeks with nicotine had significantly reduced colonic scores (1.4 +/- 0.6 and 2.2 +/- 0.15, respectively). In contrast, the jejunum was more severely damaged (2.6 +/- 0.4 and 4.0 +/- 0.3; P = 0.01, respectively). Nicotine significantly increased both somatostatin and intestinal trefoil factor mRNA expression in the colon but not in the jejunum; no effect was noted on mucin-2 or beta-actin mRNA expression. CONCLUSIONS: (1) Two weeks of nicotine administration leads to contrasting effects on jejunal and colonic inflammation in IL-10 -/- mice. (2) Nicotine ameliorated inflammation in the colon, which was associated with enhanced expression of two protective peptides.

Ontogeny and prenatal expression of trefoil factor 3/ITF in the human intestine.

BACKGROUND: Trefoil factor 3 (TFF3) or intestinal trefoil factor (ITF), a peptide normally expressed and secreted by goblet cells at the mucosal surface of the small intestine and colon, is important for the maintenance and repair of the intestinal mucosal barrier. AIM: To study the ontogeny and developmental expression of TFF3 in human intestine. SUBJECTS: We examined TFF3 expression in formalin-fixed and paraffin-embedded intestinal tissues from 24 fetuses (gestational age [GA] 12-23 weeks) and 5 adults by immunohistochemical staining. To determine whether TFF3 is excreted into the fetal intestinal tract, first-passed meconium samples were collected from 43 newborn infants (gestational age 24-41 weeks). The presence of TFF3 was examined by Western blot analysis and the relative levels of TFF3 in the meconium were quantified with a slot blot assay. RESULTS: TFF3 can be detected by immunohistochemistry in human intestine as early as 12 weeks gestation. TFF3 is present in the meconium of newborn infants; no significant difference exists in TFF3 levels in the meconium of premature infants with birth weight (BW) less than 1500 g compared to those with birth weight equal to or more than 1500 g. CONCLUSION: Premature infant's susceptibility to intestinal mucosal injury is unlikely to be explained by developmental expression of TFF3 in human intestine since secreted TFF3 is not deficient in premature infants.

Protein-losing enteropathy in ulcerative colitis.

Protein-losing enteropathy (PLE) is a debilitating potential complication of ulcerative colitis (UC). We report a case of PLE in a 26-year-old male patient with UC. The patient lost 50 pounds in the setting of a UC flare and was found to have an albumin level of 1.2 g/dl. Although the patient's UC was clinically controlled with steroids, the weight loss and hypoalbuminemia persisted with the patient's course complicated by development of deep vein thrombosis and pulmonary embolism. The diagnosis of PLE was confirmed with measurement of stool alpha-1-antitrypsin clearance. The patient's condition significantly improved following procto-colectomy.

Genomics of cardiovascular disease.

As the leading cause of death worldwide and a major cause of disability, cardiovascular disease remains a central focus of basic research, pharmacological treatment, surgical interventions, and long-term care. Inherited, monogenic syndromes have provided insight into pathophysiological mechanisms across the range of cardiovascular diseases. With the advent of post-Human Genome Project resources and technology, there has been a flood of research aimed at genome-wide predisposition markers, pharmacogenetics, and genomic signatures in complex cardiovascular disorders. Genomic research has both further elucidated the impact of genes previously identified in cardiovascular disease development and progression and discovered genomic regions as yet unknown to be associated with cardiovascular outcomes. The promise of personalized medicine lies in combining this genetic information with other biomarkers to tailor preventive and therapeutic strategies to individual patients for effective management, fewer adverse events, and preventive care.

Short-chain fatty acid induces intestinal mucosal injury in newborn rats and down-regulates intestinal trefoil factor gene expression in vivo and in vitro.

BACKGROUND: Luminal administration of short-chain fatty acids (SCFAs) induces dose-dependent intestinal mucosal injury in newborn rats. However, the mechanism underlying the injurious effects of SCFAs on intestinal mucosa in neonates is unclear. Intestinal trefoil factor (ITF) is a factor important for the maintenance and repair of the intestinal mucosal barrier. Regulation of ITF gene expression by SCFAs may be involved as one of the mechanisms. OBJECTIVES: To examine the effect of butyrate-induced colonic injury on ITF gene expression in vivo and to determine the molecular mechanisms underlying the butyrate regulation of ITF gene expression in vitro. METHODS: Whole-section colonic tissues from 9- to 10-day-old Sprague-Dawley rats that have received butyric acid at two different concentrations (150 mmol/L and 300 mmol/L) and for different time periods were processed for total RNA extraction and Northern blot analysis. Littermates that received normal saline or lactic acid at 300 mmol/L served as controls. The effect of butyrate on ITF gene expression was also examined in vitro with human colonic epithelial LS 174T cells. To further define ITF gene regulation by butyrate, transient transfection assays were performed on a 930 bp human ITF promoter-luciferase reporter gene plasmid in LS174T cells with or without the presence of butyrate. RESULTS: Concurrent with mucosal injury, butyric acid inhibited ITF gene expression in colonic tissues of newborn rats as well as in intestinal epithelial cells in a dose- and time-dependent manner. Furthermore, butyrate reduced ITF promoter report gene activity in transfected LS174T cell, suggesting that butyric acid regulation of ITF gene is by way of a specific ITF promoter. CONCLUSIONS: Butyric acid induced-intestinal mucosal injury in newborn rats is associated with down-regulation of ITF gene expression. The changes in ITF gene expression in vivo may play a role in the pathogenesis of SCFA-induced intestinal mucosal injury.

Short-chain fatty acids induce colonic mucosal injury in rats with various postnatal ages.

Short chain fatty acids (SCFAs) may play a role in the pathogenesis of neonatal necrotizing enterocolitis. To evaluate the injurious effect of SCFAs on the colonic mucosa of rats at various postnatal developmental stages, we studied a total of 170 newborn Sprague-Dawley rats at postnatal ages days 3, 9, and 23. A 1.8-F silastic catheter or umbilical catheter was inserted rectally deep into the proximal colon of the rats. Rats from each of the three postnatal age groups were randomly divided to receive one of the following distinct SCFA solutions: acetic acid, butyric acid, propionic acid, or a mixture of above SCFAs solutions. An additional subgroup of rats from each of the age groups received normal saline as a control. The concentration of each SCFA solution was 300 mM, and the pH of all solutions was adjusted to 4.0. The volume of administered solution was 0.1 mL/10 g of body weight. After 24 h, all rats were killed and the daily weight change was recorded and proximal colon was collected for histologic examination. A histologic injury score was used to quantify the severity of mucosal injury. The severity of mucosal injury induced by luminal SCFAs administration decreased as the rats matured; by postnatal day 23, the injury caused by SCFAs was minimal. Thus, the severity of the colonic mucosal injury induced by luminal SCFAs is maturation dependent; the immature state of the mucosal defense in early postnatal age in newborn rat may explain its greater vulnerability to luminal SCFAs.

Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats.

BACKGROUND: Short chain fatty acids and lactic acid are colonic bacterial fermentation products. METHODS: To evaluate the effects of these organic acids on the intestinal mucosa, a total of 72 newborn Sprague-Dawley rats (10 days old) were studied. A 3.5F catheter was inserted per rectum 4.0 cm deep into the proximal colon for organic acid administration at a volume of 0.1 ml/10 g body weight. The pH of organic acid solutions and normal saline was adjusted to 4.0. Group 1 (n = 10) received normal saline as a control. Group 2 (n = 11) received 150 mM acetic acid. Group 3 (n = 11) received 300 mM acetic acid. Group 4 (n = 10) received 150 mM butyric acid. Group 5 (n = 11) received 300 mM butyric acid. Group 6 (n = 7) received 150 mM lactic acid, and group 7 (n = 12) received 300 mM lactic acid. Animals were killed 24 hours after colonic installation of test solutions. RESULTS: Both 300 mM acetic acid and 300 mM butyric acid were associated with impaired weight gain, increased colon wet weight, and increased histologic injury scores in the colon and distal ileum (P < 0.05, analysis of variance). Both 150 mM acetic acid and butyric acid at 150 mmol/L induced minimal injury in the colon and distal ileum. Neither 150 mM nor 300 mM lactic acid induced any identifiable gross or microscopic intestinal mucosal injury. CONCLUSION: Luminal short chain fatty acids can induce dose-dependent intestinal mucosal injury in newborn rats, resembling the pathology seen in neonatal necrotizing enterocolitis. Overproduction/accumulation of short chain fatty acids, but not lactic acid, in the proximal colon and/or distal ileum may play a role in the pathogenesis of necrotizing enterocolitis in premature infants.