The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of P oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens=24 from six patients, p<0*001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the P oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis. (Gut 1995; 36: 93-99)

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal [570][571][572][573][574][575][576]

Pyoderma gangrenosum is strongly associated with inflammatory bowel disease and exhibits pathergy, occurring at sites ofprevious minor trauma. A patient is presented with a 21 year history of extensive ulcerative colitis, who developed pyoderma gangrenosum and arthralgia while receiving high dose corticosteroids for active ulcerative colitis. The arthralgia exhibited pathergy affecting particularly the left temporomandibular joint, which was stressed by an asymmetric bite, and the left elbow, which had been fractured many years previously. This prompted the hypothesis that neutrophils in this condition may be marginated, as a result of increased stickiness ofeither the neutrophil or the vascular endothelium. The introduction of heparin therapy was associated with rapid resolution ofthe arthralgia, pyoderma gangrenosum, and ulcerative colitis. (Gut 1995; 37: 585-588)

Two men with longstanding ulcerative colitis who were treated with sulphasalazine for several years and who developed chronic renal failure are reported. Renal biopsy specimens showed histological changes consistent with drug induced chronic intestinal nephritis. Extensive investigation made other causes of chronic renal failure unlikely. One of these patients underwent renal transplantation, the other has impaired but stable renal function.Case 1 A 53 year old man with total ulcerative colitis had been maintained on sulphasalazine 1 g twice a day, and was well apart from several exacerbations that required treatment with short courses of oral corticosteroids. He was not taking any other regular medication. Twenty years after onset of his colitis he complained, at routine follow up, of lethargy, nausea and anorexia, and a 2 kg weight loss. Apart from pallor, physical examination was unremarkable.Investigations showed a haemoglobin of 6.6 g/dl with a normocytic and normochromic picture and normal serum vitamin B 12, folate, and ferritin concentrations. His serum urea value was high at 29-9 mmol/l and the serum creatinine concentration was 750 ,tmol/l. A 24 hour urinary protein excretion was 0.4 g/l. Ultrasound scan showed two small kidneys with no obstructive features. Antinuclear antibody and immunoelectrophoresis were negative and serum C3, C4 values were normal.A renal biopsy specimen showed changes consistent with a drug induced intestinal nephritis. The histological changes included global sclerosis of the glomeruli, fibrosis of the interstitium, and tubular atrophy with a marked lymphocytic infiltrate.In view of the active lymphocytic infiltration he was treated with oral prednisolone and a low protein diet. The sulphasalazine was stopped.His serum creatinine fell rapidly to 320 [tmol/l from a peak level of 800 ,umol/l. His renal function is still impaired but stable.Case 2 A 61 year old man with a seven year history of total ulcerative colitis treated with sulphasalazine 1 g twice a day and intermittent corticosteroids presented with lethargy, nausea, anorexia, and weight loss. On examination he was pale and unwell.Investigations included serum sodium 139 mmol/l, potassium 4 6 mmol/l, urea 35.7 mmol/l, creatinine 973 ,umol/1, and haemoglobin 6.4 g/dl (normocytic, normochromic).

In patients with ulcerative colitis receiving maintenance 5-ASA therapy there was greater absorption and less acetylation of 5-ASA from mesalazine (Asacol) compared with sulphasalazine or olsalazine, but no evidence from this study that this resulted in increased nephrotoxicity.