gastric and duodenal ulcers . anti - inflammatory drug ( NSAID ) associated

SIR,-The role of altered colonic detoxification mechanisms in various pathophysiological conditions including ulcerative colitis and carcinogenesis cannot be overemphasised. 2 We have thus read with great interest the recent report of Ramakrishna et al about sulphation as a mechanism ofphenolic compound inactivation in human colonocytes (Gut 1991; 32: 46-9). Though the work provides valuable new information, we feel obliged to make a few critical comments. Firstly, the title and parts of the text may be misunderstood: in fact, paracetamol (acetaminophen) and not phenol sulphation has been investigated. Secondly, the mention that 'studies, on phenolic compound inactivation, using colonocytes from resected colon specimens have not been undertaken' is not entirely correct. Indeed, we have reported preliminary results about the conjugation of 1-naphthol, another phenolic compound, in human isolated colonic cell preparations.3 I-Naphthol was extensively conjugated in human colonic crypts, mainly by sulphation (75%), but also by glucuronidation (24%). These results were in agreement with those of Cohen et al in cultured human colonic mucosa,4 where normal colon predominantly sulphated 1-naphthol; in contrast, cancer tissue showed a glucuronidation predominant pattern. In the study of Ramakrishna et al paracetamol was poorly glucuronidated in normal colonocytes. This finding is not representative of the metabolic activity ofhuman colonocytes for all phenolic compounds, since l-naphthol was efficiently glucuronidated.' Moreover, this discrepancy may also come from the higher substrate concentration used by Ramakrishna et al, as it has been observed in animal species that glucuronidation is more readily saturable than sulphation.' In dialysates of patients with ulcerative colitis, a known preneoplastic condition, Ramakrishna et al found no increase of paracetamol glucuronide concentrations and a reduction of sulphated conjugates, which they interpret as an impairment of the capacity of the mucosa to sulphate phenols. However, the reduced recovery of sulphate in dialysate may alternatively be interpreted as increased paracetamol sulphate absorption.6 Moreover, reduced sulphation activity in colonocytes from ulcerative colitis patients would be at variance with other reports of enhanced biotransformation reactions.' These discrepancies between different compounds and experimental models, and the strong pathophysiological relevance of colonic biotransformation activities, emphasise the need for further studies in this field. PIERRE DECHELOTTE Policlinique Hospital Charles Nicolle, F 76031 Rouen, France MICHAEL SCHWENK AbteilungAllgemneinePharinakologie, Medizinische Hochschule Hannover, D 3000 Hannover 61, Germnany