An approach to the management of refractory ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology associated with dysregulation of the gastrointestinal mucosal immune system. It is characterized by a waxing and waning course and approximately 15% of UC patients will experience a severe episode. The first line treatment for severe colitis includes IV corticosteroids, however, 40% of patients are non-responsive to corticosteroid therapy and may require either colectomy, intravenous infliximab or intravenous cyclosporine within 3-5 days of presentation. This review focuses on the management and treatment approaches to refractory UC.

Diagnostic difficulties during combined multichannel intraluminal impedance and pH monitoring in patients with esophagitis or Barrett's esophagus.

Gastroesophageal reflux disease (GERD) is one of the most common esophageal diseases in developed countries. It is widely believed that GERD symptoms are caused by acid refluxate within the esophagus, so ambulatory 24 hour pH-monitoring became the gold standard in detecting gastroesophageal reflux. Traditional ambulatory pH monitoring is unable to detect a gastroesophageal reflux with pH >4. The introduction of multichannel intraluminal impedance and pH (MII-pH) brought new possibilities in detecting GERD. In this technique impedance identifies reflux episode whereas pH sensor further characterizes it as either acid (pH <4) or non-acid (pH > or =4). This is a great progress in diagnosing GERD but MII has also some imperfections related to pathological changes in the esophageal mucosa such as esophagitis or Barrett oesophagus, which are connecting with a very low baseline impedance values. Changes in the esophageal mucosa may also impair the esophageal motility and esophageal transit leading to some fluid retention in the esophagus. It should be stressed that very low impedance baseline creates a difficulty in interpreting the MII-pH study. In such a case it might be almost impossible to interpret the study as the interpreter does not see characteristic drop in impedance progressing either orally (reflux episode) or swallow but only almost flat impedance lines. Therefore, future studies are needed to further evaluate this problem.

Crystal structure of the promutagen O4-methylthymidine: importance of the anti conformation of the O(4) methoxy group and possible mispairing of O4-methylthymidine with guanine.

O4-Methylthymidine (O4medT) is a promutagen. To correlate its biological properties to changes in the electronic, geometric, and conformational properties of the pyrimidine base resulting from the keto to enol shift arising from methylation, an X-ray study of O4medT was undertaken. The crystal data are a = 4.950 (2) A, b = 12.648 (1) A, c = 19.305 (2) A, space group P2(1)2(1)2(1), Z = 4, and R = 0.042. The D-deoxyribofuranosyl ring is puckered in the uncommon 1T2 twist conformation with the phase angle of pseudorotation P = 133.8 (5)degrees. The amplitude of puckering tau m = 31.4 (3)degrees shows that the ring is considerably flattened. The base is in the anti conformation [chi CN = 40.6 (4)degrees], and the exocyclic C(4')-C(5') bond (psi) is gauche+ [46.2 (5)degrees]. Methylation produces cytosine-like conjugation for the thymine base. The methoxy group takes the syn-periplanar conformation. Two types of mispairings with guanine are possible, and both require the anti conformation for the O(4) methoxy group. Semiempirical energy calculations have been carried out and reveal that the anti conformation can be energetically assumed in the double helix by widening the exocyclic angles C(5)-C(4)-O(4) and C(4)-C(5)-C(7) and the angle C(4)-O(4)-C(8) at the methoxy group. Such coordinated expansion relieves unfavorable interactions between the C(7) and C(8) methyl groups.

Crystal structure of O4-methyl uridine: stacking induced changes in the geometry of the pyrimidine ring and its mutagenic role.

The geometric properties of the pyrimidine ring of O4-methyl uridine more closely resemble those of cytidine than diketo uridine. Differences between the independent molecules of O4-methyl uridine are observed in the C(7)-O(4)-C(4)-C(5)-C(6) bond orders and the planarity of the pyrimidine rings. These differences are attributed to the monopole-induced dipole interactions between the ribose ring oxygen atom and a neighboring base of molecule A. A survey of the literature reveals that similar stacking-induced effects occur in other structures, involving both pyrimidine and purines. Finally, two base pairing schemes between O4-methyl uridine and guanosine, in which two hydrogen bonds can form, have been presented. Of these two the mispair with Watson-Crick geometry is favored.