Tolerability of curcumin in pediatric inflammatory bowel disease: a forced-dose titration study.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation in the absence of a recognized etiology. The primary therapies are medications that possess anti-inflammatory or immunosuppressive effects. Given the high use of complementary alternative medicines in pediatric IBD, a prospective tolerability study of curcumin, an herbal therapy with known anti-inflammatory effects, was conducted to assess possible dosage in children with IBD. METHODS: Prospectively, patients with Crohn disease or ulcerative colitis in remission or with mild disease (Pediatric Crohn's Disease Activity Index [PCDAI] <30 or Pediatric Ulcerative Colitis Activity Index [PUCAI] score <34) were enrolled in a tolerability study. All patients received curcumin in addition to their standard therapy. Patients initially received 500 mg twice per day for 3 weeks. Using the forced-dose titration design, doses were increased up to 1 g twice per day at week 3 for a total of 3 weeks and then titrated again to 2 g twice per day at week 6 for 3 weeks. Validated measures of disease activity, using the PUCAI and PCDAI, and the Monitoring of Side Effect System score were obtained at weeks 3, 6, and 9. RESULTS: All patients tolerated curcumin well, with the only symptom that was consistently reported during all 3 visits being an increase in gassiness, which occurred in only 2 patients. Three patients saw improvement in PUCAI/PCDAI score. CONCLUSIONS: This pilot study suggests that curcumin may be used as an adjunctive therapy for individuals seeking a combination of conventional medicine and alternative medicine.

Intestinal ferroportin expression in pediatric Crohn's disease.

BACKGROUND: Anemia is a frequent complication of Crohn's disease (CD). The intestinal iron exporter ferroportin (FPN) is involved in both iron deficiency anemia and the anemia of chronic disease. To examine its role in CD, intestinal FPN expression was studied in subjects with and without CD. METHODS: Duodenal mucosal biopsies from 29 pediatric subjects with CD (n=19) and without CD (n=10) were obtained. FPN protein was measured using Western blot analysis and mRNA was assessed using quantitative real-time polymerase chain reaction (PCR). RESULTS: Intestinal FPN protein was higher in anemic CD subjects than in nonanemic CD subjects (P=0.01), while FPN mRNA levels were not different (P=0.66). In nonanemic CD subjects, erythrocyte sedimentation rate (ESR) (P=0.04), C-reactive protein (CRP) (P=0.03), and interleukin-6 (IL-6) (P=0.01) levels were elevated compared to controls. Nonanemic CD subjects had a lower median FPN protein than nonanemic controls, although it did not reach statistical significance (P=0.07). Median FPN mRNA was similar between groups (P=0.71). Although no correlation between FPN protein and IL-6 was noted, there was a strong negative correlation between serum iron and IL-6, both in subjects with CD (r=-0.88, P<0.0001) and those without anemia (r=-0.58, P=0.02). CONCLUSIONS: Intestinal FPN protein is upregulated in anemic CD subjects, suggesting that iron deficiency or anemia is the driving force regulating FPN levels. A transporter distinct from FPN appears to be involved in the hypoferremia associated with the inflammatory process of CD.

Congenital myasthenic syndrome with episodic apnea.

Congenital myasthenic syndrome is difficult to diagnose, especially in the neonate when classic myasthenic signs may not be present. Congenital myasthenic syndrome with episodic apnea is a rare cause of recurrent apnea in infancy. We present an infant with nine severe episodes of apnea in her first 6 months who underwent a prolonged evaluation before ptosis was evident, leading to a diagnosis of choline acetyltransferase deficiency, a form of congenital myasthenic syndrome. Midazolam appeared to resolve the apnea on five occasions. The diagnosis was supported by edrophonium testing and repetitive nerve stimulation. Mutation analysis demonstrated compound heterozygous p.T354M and p.A557T mutations, the latter of which is novel. The patient's respiratory status stabilized on pyridostigmine, and she is ambulatory at age 3 years. Pyridostigmine is the primary therapy for choline acetyltransferase deficiency, but the efficacy of midazolam during this patient's episodes of apnea is interesting, and warrants further study.