ABSTRACT
Fistulas manifest frequently in Crohn disease and can result in significant morbidity and often lead to the need for surgical intervention. Historically, it has been more difficult to obtain complete fistula closure in patients with perianal Crohn disease. Anti-tumor necrosis factor-alpha agents and the use of more accurate imaging modalities such as magnetic resonance imaging and rectal endoscopic ultrasound have enhanced the ability to manage fistulizing Crohn disease. A combined medical and surgical approach usually presents the best option for most patients.
ABSTRACT
BACKGROUND: L-arginine (L-Arg) is a semi-essential amino acid that is the substrate for both nitric oxide and polyamine synthesis. Cellular uptake of L-Arg is an active transport process that is subject to competitive inhibition by L-ornithine (L-Orn) and L-lysine (L-Lys). We investigated L-Arg utilization in patients with ulcerative colitis (UC). METHODS: Serum was collected from 14 normal controls and 22 UC patients with pancolitis of moderate or severe activity by histopathology score. The Mayo Disease Activity Index (DAI) and endoscopy subscore were assessed. Serum amino acid levels were measured by high-performance liquid chromatography. Arginine availability index (AAI) was defined as [L-Arg]/([L-Orn] + [L-Lys]). RESULTS: Serum L-Arg levels were significantly associated with histopathologic grade (P = 0.001). L-Arg levels were increased in subjects with severe colitis when compared to those with moderate colitis or normal mucosa. L-Orn + L-Lys levels were also increased in severe colitis, so that AAI was not significantly increased. L-Arg levels were also strongly associated with the endoscopy subscore (P < 0.001). There was a strong correlation between DAI and L-Arg levels (r = 0.656, P < 0.001). CONCLUSIONS: Serum L-Arg levels correlate with UC disease severity but availability is not increased due to competitive inhibition by L-Orn and L-Lys. Our findings suggest that L-Arg uptake by cells in the inflamed colon is defective, which may contribute to the pathogenesis of UC. Studies delineating the mechanism of uptake inhibition could enhance our understanding of UC or lead to novel treatment options.
Subject(s)
Arginine/blood , Biomarkers/blood , Colitis, Ulcerative/blood , Colitis, Ulcerative/diagnosis , Colon/pathology , Adolescent , Adult , Aged , Case-Control Studies , Chromatography, High Pressure Liquid , Female , Humans , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
Fistulas manifest frequently in Crohn disease and can result in significant morbidity and often lead to the need for surgical intervention. Historically, it has been more difficult to obtain complete fistula closure in patients with perianal Crohn disease. Anti-tumor necrosis factor-alpha agents and the use of more accurate imaging modalities such as magnetic resonance imaging and rectal endoscopic ultrasound have enhanced the ability to manage fistulizing Crohn disease. A combined medical and surgical approach usually presents the best option for most patients.
