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SUMMARY Galanin, a newly discovered peptide, was found throughout the gastrointestinal tract of man, pig, and rat, exclusively in nerves. The concentrations of immunoreactive galanin ranged from 3-7±0-7 (mean±SEM) pmollg in rat antrum to 76-5±14-3 pmol/g in pig colon. The predominantly intrinsic origin of the galanin nerves was shown by the finding of the peptide in submucosal ganglion cells, the majority of which also contained VIP. Furthermore, neither extrinsic denervation of the gut nor administration of capsaicin, which selectively destroys extrinsic afferent fibres, had any significant effect on the galanin innervation. The caudal projection of galanin-immunoreactive fibres was demonstrated by complete transection of the gut, which led to their reduction in the 1 to 2 cm distal to the cut. The abundance of galanin in the innervation of the mammalian gut and its reported action on smooth muscle contractility suggest this peptide to be a novel regulatory factor in the control of bowel function.The system of mammalian regulatory peptides continues to expand with the discovery of new active molecules. One of the latest peptides to be isolated and characterised has been termed galanin.' The name of this 29 amino acid peptide was derived from the fact that its N-and C-terminal residues are glycine and alanine, respectively. Galanin has been reported to occur in rat brain and in the intestinal tract of mice, rats, guinea pigs, and pigs.2 3 As yet, little is known about the actions of galanin but preliminary pharmacological experiments have shown that it causes smooth muscle contraction in rat gut and induces mild hyperglycaemia.' 4 In the present study, the techniques of immunocytochemistry and radioimmunoassay were used in combination to determine the distribution of galanin in the human, porcine and rodent gastrointestinal tracts and, using surgical and pharmacological manipulations, to examine the origin, projections and nature of galanin-containing nerves in the gut of the rat. Fresh specimens of human bowel (fundus, n=8; antrum, n=11; duodenum, n=10; jejunum, n=4; ileum, n=3 (for immunocytochemistry only) and colon, n=10) were obtained at surgery from segments of bowel resected for carcinoma or duodenal ulcer. From each specimen, full thickness samples were taken from macroscopically and histologically normal areas at least 8 cm from the tumour margin. In addition, specimens of antrum, fundus, duodenum, jejunum, ileum and colon were obtained from five rats and nine pigs. All normal tissues were processed for immunocytochemistry and radioimmunoassay. SURGICAL PROCEDURES (a) Extrinsic denervationIn order to determine whether enteric galaninimmunoreactive nerves have an intrinsic and/or extrinsic origin, portions of rat gut were extrinsically denervated. Six rats (Sprague-Dawley) were anaesthetised with sodium pentabarbitone (20 mg/kg ip). The abdomen was opened and the terminal ileum 849 on 9 May 2018 by guest. Protected by copyright.

The kinetics of 13CO2 have been investigated following oral administration at five doses between 12.5 and 100 mg of 13C labelled sodium bicarbonate to 10 healthy subjects in a randomized study. Sodium bicarbonate in this study served as a model compound for carbon dioxide/bicarbonate generated in breath tests. Exhalation of 13CO2 into breath was monitored by stable isotope ratio mass spectrometry. The kinetics of 13CO2 were characterized by an apparent terminal elimination half-life of 1 h and a mean recovery of 0.630 of the dose administered. The kinetics were not dose-dependent. These results were in agreement with the findings reported previously after i.v. application of sodium bicarbonate.

Galanin immunoreactivity was measured by RIA, using antibodies directed against both the non-C- and C-terminal positions of porcine galanin, in tissue extracts of normal adrenals and pheochromocytomas and also in the plasma of normal subjects and patients with pheochromocytomas. No C-terminal galanin-like immunoreactivity was detected in plasma or tissue, suggesting differences in the amino acid sequence of human compared with porcine galanin. A non-C-terminally directed antibody was, therefore, used to characterize human galanin immunoreactivity by gel permeation chromatography and reverse phase high pressure liquid chromatography and to localize it by immunocytochemistry. The galanin content of whole adrenal gland was 2.6 +/- 0.9 (+/- SEM) pmol/g (n = 5). In contrast, however, pheochromocytomas had much greater concentrations (21 +/- 2.3 pmol/g; n = 16). Gel chromatography and reverse phase high pressure liquid chromatography revealed 2 molecular forms of galanin immunoreactivity with identical elution positions in both normal adrenals and tumors. The concentration of galanin in plasma from both normal subjects and pheochromocytoma patients was below the detection limit of the assay (less than 10 pmol/liter). Using immunocytochemistry, galanin was localized to scattered cells or clusters of tumor cells in 5 of 11 pheochromocytomas and only a few chromaffin cells and cortical nerve fibers in normal adrenals.

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The influence of a standard breakfast on the single-dose pharmacokinetics of zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied in 27 subjects with advanced human immunodeficiency virus infection (Centers for Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide metabolite (GAZT) [B]). Recoveries (AZT and GAZT) in urine varied with both dosages, reflecting more a problem of accounting for the metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5% [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in human immunodeficiency virus-infected subjects is extremely variable, with a high degree of interindividual differences. Furthermore, breakfast had a marked influence on the absorption of AZT, suggesting that the drug should be taken in a fasting state.

The excellent sensitivity and specificity of the urea breath test9 101718 and its simplicity make it an ideal method for screening people for H pylori colonisation. Thus we evaluated 100 healthy adults with a broad age range for past or active H pylori infection using serology and the urea breath test. Patients and methods PATIENTSOne hundred people aged 20 to 92 participated in this study. All were healthy and were invited by the investigators to participate. They were recruited from family members, friends, and relatives of the investigators and fellow workers. None had a history of chronic dyspepsia, peptic ulcers, or gastric or other abdominal surgery except for appendicitis; none had taken antacids, a bismuth preparation, or other drugs for dyspepsia within the previous year, and none had taken antibiotics within the three months before the study. The protocol was approved by the University of Basel Ethical Committee and each subject gave written informed consent.'3C-UREA BREATH TEST All breath tests were performed in the morning after an overnight fast according to the method used and validated previously'0; Dill et al have shown that the urea breath test has a sensitivity and specificity of 97% and 100%, respectively.'0 Briefly, the subjects drank 150 ml of a liquid test meal to delay gastric emptying and subsequently 150 mg '3C-urea dissolved in 20 ml of tap water. 'C-urea (99% '3C) was purchased as a crystalline substance (Tracer Technologies Inc, Somerville MA, USA). The test meal we used was a 25% glucose polymeric solution that was prepared as a powder (glucose 4 g, maltose 2 g, polysaccharide 30 g, citric acid 0.2 g) in 250 ml bottles and dissolved with 150 ml of tap water immediately before use. Two breath samples were obtained at baseline and then every 15 min for up to 60 min and stored in silicon-coated, evacuated 20 ml glass tubes (vacutainers) for later analysis. Excess '3C02 in breath samples was measured by isotope ratio mass spectrometry (Sira 10, VG