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F2-isoprostanes are prostaglandin-like compounds derived from nonenzymatic free radical-catalyzed peroxidation of arachidonic acid. 8-epi-Prostaglandin (PG) F2alpha, a major component of the F2-isoprostane family, can be conveniently measured in urine to assess noninvasively lipid peroxidation in vivo. Measurement of major metabolites of endogenous 8-epi-PGF2alpha, in addition to the parent compound, may be useful to better define its formation in vivo. 2,3-Dinor-5,6-dihydro-8-epi-PGF2alpha is the only identified metabolite of 8-epi-PGF2alpha in man, but its endogenous levels are unknown. In addition to this metabolite, we have identified another major endogenous metabolite, 2,3-dinor-8-epi-PGF2alpha, in human and rat urine. The identity of these compounds, present at the pg/ml level in urine, was proven by a number of complementary approaches, based on: (a) immunoaffinity chromatography for selective extraction; (b) gas chromatography-mass spectrometry for structural analysis; (c) in vitro metabolism in isolated rat hepatocytes; and (d) chemical synthesis of the enantiomer of 2,3-dinor-5, 6-dihydro-8-epi-PGF2alpha as a reference standard. In humans, the urinary excretion rate of both dinor metabolites is comparable with that of 8-epi-PGF2alpha. Both metabolites increase in parallel with the parent compound in cigarette smokers, and they are not reduced during cyclooxygenase inhibition. Another beta-oxidation product, 2, 3,4,5-tetranor-8-epi-PGF2alpha, was identified as a major product of rat hepatocyte metabolism. In conclusion, at least two major beta-oxidation products of 8-epi-PGF2alpha are present in urine, which may be considered as additional analytical targets to evaluate 8-epi-PGF2alpha formation and degradation in vivo.

In 23 patients with dermatitis herpetiformic (DH) and five patients with linear-IgA bullous dermatosis (BD) we evaluated the occurrence of histologic jejunal changes and small-bowel function abnormalities. None of the patients showed clinical signs or symptoms of malabsorption. Morphological jejunal changes consistent with gluten-sensitive enteropathy were found in 82 of DH patients and in 60 of DD patients. However, DD patients showed only mild jejunal histologic abnormalities, whereas more severe jejunal lesions were found in most patients with DH. Functional tests showed a rough correlation with the severity of the jejunal lesions, being almost completely normal in BD patients and DH patients with mild intestinal damage, whereas most of DH patients with subtotal or total villous atrophy showed abnormal d-xylose tests and folic acid assays. Lactose tolerance tests (H2breath test and blood glucose after oral lactose load) showed no correlation with the degree of jejunal damage.

To set up and characterize reproducible, long-standing small intestinal inflammation in rats, animals were given three different oral regimens of indomethacin (Ind): a bolus of 10 mg/kg in water and three daily doses of 2, 4, and 8 mg/kg Ind in (a) the drinking water or (b) the standard diet. The effect of Ind on the small intestine was monitored by measuring intestinal permeability (IP). The three-day regimen seemed more suitable than a bolus dose to induce long-standing inflammatory modifications in the rat small intestine and Ind administered in the drinking water gave more consistent modifications of IP and more reproducible results than Ind in food. IP seemed a suitable tool for detecting these inflammatory changes in the small-intestinal physiology. This model could be used to assess the effect of new drugs on inflammation.

The role of lactose malabsorption (LM) was investigated in 32 children (mean age 8.13 ± 2.46 years) with recurrent abdominal pain (RAP). LM was detected in 75 of them by a lactose breath hydrogen test (LBHT) after a 2-g/kg (max 50-g) load. Of the 18 malabsorbers who participated in a 3-month lactose-free diet (LFD), 14 were judged “improved” and reported lower pain frequency (p < 0.001). The malabsorbers who improved versus the not improved had comparable past lactose ingestion but were distinguishable on the basis of their lactose absorption capacity (0.36 vs. 0.81 g/kg; p < 0.01), as subsequently determined by multiple LBHTs with 25-, 12.5-, and 6-g loads. The ratio between past lactose ingestion and lactose absorption was 1.89 in the improved and 0.55 in the not improved groups (p < 0.01), retrospectively indicating lactose as a possible cause of the symptoms in the improved group. The reintroduction of lactose in amounts not exceeding the absorption capacity into the diet of each malabsorber who had improved with LFD caused relapse in none of the 14 subjects monitored for 2–6 months. In conclusion, LM seems an important cause of symptoms in Italian children with RAP. Assessment of the lactose absorption threshold of each subject of LBHTs provides a basis for reintroduction of “calibrated” amounts of lactose-containing foods (e.g., milk) into the diet.

To set up and characterize reproducible, long-standing small intestinal inflammation in rats, animals were given three different oral regimens of indomethacin (Ind): a bolus of 10 mg/kg in water and three daily doses of 2, 4, and 8 mg/kg Ind in (a) the drinking water or (b) the standard diet. The effect of Ind on the small intestine was monitored by measuring intestinal permeability (IP). The three-day regimen seemed more suitable than a bolus dose to induce long-standing inflammatory modifications in the rat small intestine and Ind administered in the drinking water gave more consistent modifications of IP and more reproducible results than Ind in food. IP seemed a suitable tool for detecting these inflammatory changes in the small-intestinal physiology. This model could be used to assess the effect of new drugs on inflammation.

The role of lactose malabsorption (LM) was investigated in 32 children (mean age 8.13 ± 2.46 years) with recurrent abdominal pain (RAP). LM was detected in 75% of them by a lactose breath hydrogen test (LBHT) after a 2-g/kg (max 50-g) load. Of the 18 malabsorbers who participated in a 3-month lactose-free diet (LFD), 14 were judged “improved” and reported lower pain frequency (p < 0.001). The malabsorbers who improved versus the not improved had comparable past lactose ingestion but were distinguishable on the basis of their lactose absorption capacity (0.36 vs. 0.81 g/kg; p < 0.01), as subsequently determined by multiple LBHTs with 25-, 12.5-, and 6-g loads. The ratio between past lactose ingestion and lactose absorption was 1.89 in the improved and 0.55 in the not improved groups (p < 0.01), retrospectively indicating lactose as a possible cause of the symptoms in the improved group. The reintroduction of lactose in amounts not exceeding the absorption capacity into the diet of each malabsorber who had improved with LFD caused relapse in none of the 14 subjects monitored for 2–6 months. In conclusion, LM seems an important cause of symptoms in Italian children with RAP. Assessment of the lactose absorption threshold of each subject of LBHTs provides a basis for reintroduction of “calibrated” amounts of lactose-containing foods (e.g., milk) into the diet.

Gastric carbonic anhydrase (CA) is believed to play an important role related to cytoprotection, and duodenogastric reflux of bile salts (BS) is suspected of having a causal role in many pathologic conditions. Thus, we decided to investigate the effect of free and conjugated BS on human and rat gastric CA activity. Cholate exerted the most potent inhibitory activity on both human (I50 = 2.24 mM) and rat (I50 = 1.68 mM) gastric CA, followed by glycochenodeoxycholate and taurocholate (I50 = 6.90 mM and 13.67 mM on rat gastric CA). Human and rat whole bile produced 10-90% and 20-40% inhibition of gastric CA of the same species. Since the concentrations of free and conjugated BS tested in this study can be found in the postgastrectomized stomach, our data suggest that inhibition of gastric CA might be one mechanism contributing to the gastric mucosa damage caused by BS refluxing into the stomach after gastric surgery.