Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs.

Measurements of luminal pH in the normal gastrointestinal tract have shown a progressive increase in pH from the duodenum to the terminal ileum, a decrease in the caecum, and then a slow rise along the colon to the rectum. Some data in patients with ulcerative colitis suggest a substantial reduction below normal values in the right colon, while limited results in Crohn's disease have been contradictory. Determinants of luminal pH in the colon include mucosal bicarbonate and lactate production, bacterial fermentation of carbohydrates and mucosal absorption of short chain fatty acids, and possibly intestinal transit. Alterations in these factors, as a result of mucosal disease and changes in diet, are likely to explain abnormal pH measurements in inflammatory bowel disease (IBD). It is conceivable that reduced intracolonic pH in active ulcerative colitis impairs bioavailability of 5-aminosalicylic acid from pH dependent release formulations (Asacol, Salofalk) and those requiring cleavage by bacterial azo reductase (sulphasalazine, olsalazine, balsalazide), but further pharmacokinetic studies are needed to confirm this possibility. Reports that balsalazide and olsalazine may be more efficacious in active and quiescent ulcerative colitis, respectively, than Asacol suggest that low pH may be a more critical factor in patients taking directly pH dependent release than azo bonded preparations. Reduced intracolonic pH also needs to be considered in the development of pH dependent colonic release formulations of budesonide and azathioprine for use in ulcerative and Crohn's colitis. This paper reviews methods for measuring gut pH, its changes in IBD, and how these may influence current and future therapies.

Central-peripheral transitional zone of the spinal accessory nerve in the rat.

The spinal accessory nerve rootlets emerge from the lateral aspect of the upper five segments of the cervical spinal cord underlying the nerve trunk. They cross the lateral funiculus of the cord with a slight rostral inclination. Here some pursue a relatively straight course while others have a dorsal convexity. The transitional zones may be classified into three distinct types, related to their orientation as they traverse the glia limitans to emerge as free rootlets. The fibres in Type 1 rootlets bend sharply rostrally on reaching the glia limitans. Type 2 rootlets turn ventrally to run in the glia limitans in the transverse plane of the cord before emerging. Type 3 rootlets are found only at C1. Their fibres initially turn caudally in the glia limitans and then loop rostrally. The morphology of the central-peripheral transitional zones of the spinal accessory rootlets closely resembles that of cervical ventral rootlets, and is therefore correlated with the motor function of these rootlets rather than with their intermediate location between the ventral and dorsal cervical rootlets.