BACKGROUND: Congestive ischemic colitis is a rare subtype of ischemic colitis with an unknown pathophysiology. Excluding conservative management, such as fasting, no established treatment exists; therefore, surgical intervention should be considered in some cases if symptoms worsen. Current literature suggests that anti-inflammatory agents may effectively treat congestive ischemic colitis.
METHODS: We present the case of a 68-year-old female patient who underwent laparoscopic left hemicolectomy for transverse colon cancer 3 years ago. Postoperatively, follow-up included an annual colonoscopy and abdominal computed tomography (CT) at a local clinic. However, progressive erythema and edema of the sigmoid colon were observed 1 year postoperatively. Upon admission to our hospital, she complained of abdominal pain and diarrhea. Abdominal CT showed thickening of the sigmoid colon walls, and colonoscopy revealed erythema, edema, and multiple ulcers with exudate in the sigmoid colon. CT angiography showed engorgement of the sigmoid vasa recta without any vascular abnormalities. The diagnosis was congestive ischemic colitis, and we treated the patient with anti-inflammatory agents. After 2 mo of glucocorticoid therapy (20 mg once daily) and 7 mo of 5-aminosalicylate therapy (1 g twice daily), the ulcers completely healed. She has not experienced any recurrence for 2 years.
CONCLUSIONS: Anti-inflammatory therapy, specifically glucocorticoids and 5-aminosalicylate, has demonstrated promising efficacy and introduces potential novel treatment options for congestive ischemic colitis.

UNASSIGNED: Notably, 5-aminosalicylates (5-ASA) are vital in treating inflammatory bowel diseases (IBD). The adverse events of 5-ASA rarely occur but they could be fatal.
UNASSIGNED: We aimed to discover new genetic biomarkers predicting 5-ASA-induced adverse events in patients with IBD.
UNASSIGNED: This was a retrospective observational study.
UNASSIGNED: We performed a genome-wide association study on patients with IBD in South Korea. We defined subset 1 as 39 all adverse events and 272 controls; subset 2 as 20 severe adverse events and 291 controls (mild adverse events and control); subset 3 as 20 severe adverse events and 272 controls; and subset 4 as 19 mild adverse events and 272 controls. Logistic regression analysis was performed and commonly found associated genes were determined as candidate single-nucleotide polymorphisms predicting 5-ASA adverse events.
UNASSIGNED: Patients with Crohn\'s disease (CD) were significantly negatively associated with the development of adverse events compared to patients with ulcerative colitis (UC) (5.3% versus 22.9%). However, sex and age at diagnosis were unassociated with the adverse events of 5-ASA. rs13898676 [odds ratio (OR), 20.33; 95% confidence interval (CI), 5.69-72.67; p = 3.57 × e-6], rs12681590 (OR, 7.35; 95% CI, 2.85-19.00; p = 3.78 × e-5), rs10967320 (OR, 4.51; 95% CI, 2.18-9.31; p = 4.72 × e-5), and rs78726924 (OR, 3.54; 95% CI, 1.69-7.40; p = 7.96 × e-5) were genetic biomarkers predicting 5-ASA-induced severe adverse events in patients with IBD.
UNASSIGNED: The adverse events of 5-ASA were more common in patients with UC than those with CD in our study. We found that novel rs13898676 nearby WSB2 was the most significant genetic locus contributing to 5-ASA\'s adverse event risk.

Two aminosalicylate isomers have been found to possess useful pharmacological behavior: p-aminosalicylate (PAS, 4AS) is an anti-tubercular agent that targets M. tuberculosis, and 5-aminosalicylate (5AS, mesalamine, mesalazine) is used in the treatment of ulcerative colitis (UC) and other inflammatory bowel diseases (IBD). PAS, a structural analog of pABA, is biosynthetically incorporated by bacterial dihydropteroate synthase (DHPS), ultimately yielding a dihydrofolate (DHF) analog containing an additional hydroxyl group in the pABA ring: 2\'-hydroxy-7,8-dihydrofolate. It has been reported to perturb folate metabolism in M. tuberculosis, and to selectively target M. tuberculosis dihydrofolate reductase (mtDHFR). Studies of PAS metabolism are reviewed, and possible mechanisms for its mtDHFR inhibition are considered. Although 5AS is a more distant structural relative of pABA, multiple lines of evidence suggest a related role as a pABA antagonist that inhibits bacterial folate biosynthesis. Structural data support the likelihood that 5AS is recognized by the DHPS pABA binding site, and its effects probably range from blocking pABA binding to formation of a dead-end dihydropterin-5AS adduct. These studies suggest that mesalamine acts as a gut bacteria-directed antifolate, that selectively targets faster growing, more folate-dependent species.

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.

Mesalamine (5-ASA) is the mainstay therapy in patients with mild-to-moderate active ulcerative colitis (UC). However, non-adherence to therapy and practice variability among gastroenterologists represent long-standing barriers, leading to poor outcomes. Additionally, targets to treat in UC are increasingly evolving from focusing on clinical remission to achieving endoscopic and histological healing. To date, systemic steroids are still recommended in non-responders to 5-ASA, despite their well-known side effects. Importantly, with the advent of new therapeutic options such as oral corticosteroids with topical activity (e.g., budesonide multimatrix system (MMX)), biologics, and small molecules, some issues need to be addressed for the optimal management of these patients in daily clinical practice. The specific positioning of these drugs in patients with mild-to-moderate disease remains unclear. This review aims to identify current challenges in clinical practice and to provide physicians with key strategies to optimize treatment of patients with mild-to-moderate UC, and ultimately achieve more ambitious therapeutic goals.

Ulcerative colitis and Crohn\'s disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn\'s and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn\'s disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn\'s disease, including patients, their families and friends.

OBJECTIVE: In some patients with ulcerative proctitis (UP), skip inflammation is noted in the right side of the colon, but little is known about its clinical course. The aim of this study was to evaluate the clinical course of UP with skip inflammation and the efficacy of topical 5-aminosalicylate (5-ASA) monotherapy.
METHODS: This study reviewed the data of 388 patients with an initial diagnosis of UP from January 2005 to October 2015. This study matched each UP patient with skip inflammation 1:2 with controls who had UP without skip inflammation; to reduce bias, this study matched the controls with the cases by age, gender, and initial disease activity.
RESULTS: During the follow-up period (median: 69.5 months), the overall progression rates for the control group (n = 192) and the skip inflammation group (n = 96) were 24.0% and 32.9% at 10 years, respectively (log-rank P = 0.71). In the skip inflammation group, the progression rates were not significantly different between the 5-ASA combination group and the topical group, 33.4% and 26.6% at 10 years, respectively (log-rank P = 0.96). The overall acute exacerbation rates for the control and skip inflammation groups were 17.2% and 26.8% at 10 years, respectively (log-rank P = 0.68). In the skip inflammation group, the exacerbation rates were also not significantly different between the combination and topical treatment groups, 26.6% and 23.6% at 10 years, respectively (log-rank P = 0.88).
CONCLUSIONS: The clinical course of UP with skip inflammation was not different from that of typical UP, and topical 5-ASA monotherapy for maintaining remission was as effective as 5-ASA combination therapy irrespective of the presence of skip lesions.

The 1,125-bp mabB gene encoding 5-aminosalicylate (5ASA) 1,2-dioxygenase, a nonheme iron dioxygenase in the bicupin family that catalyzes the cleavage of the 5ASA aromatic ring to form cis-4-amino-6-carboxy-2-oxohexa-3,5-dienoate in the biodegradation of 3-aminobenzoate, was cloned from Comamonas sp. strain QT12 and characterized. The deduced amino acid sequence of the enzyme has low sequence identity with that of other reported ring-cleaving dioxygenases. MabB was heterologously expressed in Escherichia coli cells and purified as a His-tagged enzyme. The optimum pH and temperature for MabB are 8.0 and 10°C, respectively. FeII is required for the catalytic activity of the purified enzyme. The apparent Km and Vmax values of MabB for 5ASA are 52.0 ± 5.6 μM and 850 ± 33.2 U/mg, respectively. The two oxygen atoms incorporated into the product of the MabB-catalyzed reaction are both from the dioxygen molecule. Both 5ASA and gentisate could be converted by MabB; however, the catalytic efficiency of MabB for 5ASA was much higher (∼70-fold) than that for gentisate. The mabB-disrupted mutant lost the ability to grow on 3-aminobenzoate, and mabB expression was higher when strain QT12 was cultivated in the presence of 3-aminobenzoate. Thus, 5ASA is the physiological substrate of MabB.IMPORTANCE For several decades, 5-aminosalicylate (5ASA) has been advocated as the drug mesalazine to treat human inflammatory bowel disease and considered the key intermediate in the xenobiotic degradation of many aromatic organic pollutants. 5ASA biotransformation research will help us elucidate the microbial degradation of these pollutants. Most studies have reported that gentisate 1,2-dioxygenases (GDOs) can convert 5ASA with significantly high activity; however, the catalytic efficiency of these enzymes for gentisate is much higher than that for 5ASA. This study showed that MabB can convert 5ASA to cis-4-amino-6-carboxy-2-oxohexa-3,5-dienoate, incorporating two oxygen atoms from the dioxygen molecule into the product. Unlike GDOs, MabB uses 5ASA instead of gentisate as the primary substrate. mabB is the first reported 5-aminosalicylate 1,2-dioxygenase gene.

We investigate the inhibitory effect of marketed drugs for treatment of inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn\'s disease (CD) on the uptake transporters of peptide transporter 1 (PEPT1), which are up-regulated under the inflamed condition. The uptake transport of glycylsarcosine, a typical substrate for PEPT1, was reduced to 60% only by 5-aminosalicylate at the clinically relevant concentration among tested marketed drugs in PEPT1 transfected HEK293 cell lines. These findings suggest that the inhibition of PEPT1, which were up-regulated in inflamed or non-inflamed site on UC and CD patients, contribute to the clinical effect of commercially available drugs for IBD patients through the inhibition of uptake of antigenic proinflammatory oligopeptides such as formyl-methionine (Met)-leucine (Leu)-phenylalanine (Phe) via PEPT1.

5-Aminosalicylates are a class of anti-inflammatory agents that have been used for decades in inflammatory bowel disease. Whilst they are first line for induction and an option for maintenance of remission in ulcerative colitis, the picture in Crohn\'s disease is variable. For maintenance of remission, key Cochrane systematic reviews have found conflicting results between the medical and surgical induced contexts. In this piece, the possible reasons for this are considered. It is proposed that clinicians should consider 5-aminosalicylates agents an option to maintain remission post-surgery. Future primary research is needed in the medical induced remission setting which considers the length of remission on enrolment and endoscopic or histological disease scores. Additionally, secondary research to rank the various treatment options in the post-surgical setting could be achieved through the use of network meta-analysis and will guide policy makers in the future.