Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: responders versus nonresponders.

AIM: To explore rectal nitric oxide (NO) as biomarker of treatment response in ulcerative colitis (UC) and Crohn's disease (CD), and examine relationships between rectal NO, mucosal expression of NO synthases (NOS), and pro-inflammatory cytokines. METHODS: Twenty-two patients with UC and 24 with CD were monitored during steroid treatment. Rectal NO levels were measured and clinical activities were assessed on days 1, 3, 7 and 28. Mucosal presence of NOS and pro-inflammatory cytokines were analyzed by immunohistochemistry and RT-PCR. RESULTS: Active UC and CD displayed markedly increased rectal NO levels (10950 +/- 7610 and 5040 +/- 1280 parts per billion (ppb), respectively) as compared with the controls (154 +/- 71 ppb, P < 0.001). Rectal NO correlated weakly with disease activity in both UC and CD (r = 0.34 for UC and r = 0.48 for CD, P < 0.01). In 12 patients, a steroid-refractory course led to colectomy. These patients had only slightly increased NO levels (UC: 620 +/- 270 ppb; CD: 1260 +/- 550 ppb) compared to those with a therapeutic response (UC: 18860 +/- 530 ppb, P < 0.001; CD: 10060 +/- 3200 ppb, P < 0.05). CONCLUSION: Rectal NO level is a useful biomarker of treatment response in IBD as low NO levels predicts a poor clinical response to steroid treatment.

Measurement of nitric oxide may differentiate between inflammatory and non-inflammatory prostatitis.

OBJECTIVE: The majority of patients with prostatitis have chronic non-bacterial prostatitis/chronic pelvic pain syndrome of inflammatory type (Category IIIA) or non-inflammatory type (Category IIIB), based on the National Institutes of Health classification. The aim of this study was to investigate whether measurement of nitric oxide (NO) formation in the prostatic urethra can be used as a marker for inflammation in the evaluation of patients with chronic prostatitis/pelvic pain syndrome. MATERIAL AND METHODS: A total of 25 men with prostatitis were examined. In 8 patients >10 white blood cells/high-power field (WBC/hpf) were found in expressed prostatic secretion (EPS) (Category IIIA), whereas the other 17 had no signs of inflammation (Category IIIB). NO production was measured using a silicon catheter, with the catheter balloon being placed in the prostatic urethra. Room air (5 ml) was incubated for 5 min and analyzed. NO formation in the urinary bladder was also measured. RESULTS: The NO concentration in the prostatic urethra was significantly higher in the 8 patients with >10 WBC/hpf than in those with <10 WBC/hpf. The NO concentration in the urinary bladder was low in both groups. CONCLUSIONS: We found an elevated NO concentration in the prostatic urethra in patients with >10 WBC/hpf in the EPS but not in those with <10 WBC/hpf, which supports the theory of different pathogeneses for Categories IIIA and IIIB. Measurement of NO production in the prostatic urethra can be used to discriminate between the two categories and as the method is easy and fast it may represent an attractive alternative to the four-glass test.

Rectal mucosal nitric oxide in differentiation of inflammatory bowel disease and irritable bowel syndrome.

BACKGROUND & AIMS: Differentiating patients with functional bowel disorders from those with inflammatory bowel disease (IBD) can be difficult. Rectal luminal levels of nitric oxide (NO) are greatly increased in IBD. To further evaluate this disease marker, we compared NO in patients with irritable bowel syndrome (IBS) with those found in patients with active IBD and in healthy control subjects. METHODS: Rectal NO was measured with chemiluminescence technique by using a tonometric balloon method in 28 healthy volunteers, 39 patients with IBS, 86 with IBD (Crohn's disease and ulcerative colitis), and 12 patients with collagenous colitis. In addition, NO was measured before and after a 4-week treatment period in patients with active ulcerative colitis and repeatedly during 2 weeks in healthy volunteers. RESULTS: NO was low in healthy control subjects (median, 45; 25th-75th percentile, 34-64 parts per billion [ppb]), and variations over time were small. In IBS patients NO was slightly increased (150, 53-200 ppb; P < .001), whereas patients with active IBD or collagenous colitis had greatly increased NO levels (3475, 575-8850 ppb, and 9950, 4475-19,750 ppb, respectively; P < .001). With a cutoff level of 250 ppb, NO had a sensitivity of 95% and a specificity of 91% in discriminating between active bowel inflammation and IBS. Rectal NO correlated with disease activity in IBD and collagenous colitis and decreased markedly in IBD patients responding to anti-inflammatory treatment. CONCLUSIONS: Rectal NO is a minimally invasive and rapid tool for discriminating between active bowel inflammation and IBS and a possibly useful add-on for monitoring patients with IBD.

Increased rectal nitric oxide in children with active inflammatory bowel disease.

BACKGROUND: Luminal nitric oxide increases in ulcerative colitis and Crohn disease. The authors have previously used a minimally invasive method to demonstrate increased luminal nitric oxide in ulcerative colitis and Crohn disease of the colon. The aim of the current study was to determine whether this method could be applied to identify inflammatory activity in ulcerative colitis and Crohn disease in children. METHODS: Thirty-six children (18 of whom had active disease) with inflammatory bowel disease localized to the colon were studied. The control group comprised 12 healthy children. To measure nitric oxide, a silicon catheter with an inflatable balloon was inserted into the rectum and inflated with 10 mL of nitric oxide-free air. After a 10-minute incubation time, the air was withdrawn and nitric oxide concentrations were immediately analyzed using a chemiluminescence technique. RESULTS: Children with active ulcerative colitis and Crohn disease of the colon had greatly increased luminal nitric oxide concentrations in the rectum (8,840 +/- 5,120 and 15,170 +/- 4,757 parts per billion [ppb], respectively) compared with controls (77 +/- 17 ppb) (P < 0.001). Children with nonactive ulcerative colitis or Crohn disease displayed low concentrations of rectal nitric oxide (356 +/- 110 and 188 +/- 55 ppb, respectively), which was not different from that of healthy controls. CONCLUSION: Rectal nitric oxide measurement is a feasible and useful method for monitoring disease activity in inflammatory bowel disease, especially in children.