Background-Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role. Aims-In order to ascertain whether free radical mediated oxidative DNA damage is involved in such a process, concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect measure of free radical mediated damage, were determined in biopsy specimens from patients undergoing endoscopy. Patients-Eighty eight patients were divided into histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaVected controls. Methods-Intestinal metaplasia, Helicobacter pylori infection, and disease activity were semiquantitatively scored. 8OHdG concentrations were assessed by HPLC with electrochemical detection, and TBARS concentrations were fluorimetrically assayed. Results-8OHdG concentrations (mean number of adducts/105 dG residues) were significantly higher in chronic atrophic gastritis (p=0.0009). Significantly higher concentrations were also detected in the presence of severe disease activity (p=0.02), intestinal metaplasia (p=0.035), and H pylori infection (p=0.001). TBARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 8OHdG concentrations correlated best with the presence and severity of H pylori infection (r=0.53, p=0.002). Conclusions-Chronic gastritis is characterised by the accumulation of oxidative DNA damage with mutagenic and carcinogenic potential. H pylori infection is the major determinant for DNA adduct formation.

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Circulating leptin concentrations are shown to be influenced not only by hormones, but also by body weight and energy balance. High altitude (HA) exposure induces a daily negative energy balance and stress hormone activation. The aim of our study was to evaluate leptin concentration during both acute and prolonged HA exposure and its correlations with some metabolic and hormonal parameters. Twelve males were studied during a stay at HA (15-20 days at 5,050 m). Blood samples for serum leptin, plasma insulin and 24-h urinary epinephrine (E) and norepinephrine (NE) were collected at sea level (SL), at the arrival at HA (A) and after 12-16 days (C) of stay. Symptoms of Acute Mountain Sickness (AMS) were evaluated using the Lake Louise score and the results showed there was no relationship with leptin concentrations. During the stay, both body mass index and leptin levels significantly decreased in both groups [leptin from 1.88 (1.12) to 1.21 (1.04) ng/ml, P<0.008, in A; and to 1.06 (0.74) ng/ml, P<0.003, in C]. Acute HA exposure induced a clear-cut significant increase of NE ( P<0.001 in A, P<0.003 in C) while E and insulin levels were unchanged in both phases. Moreover, a significant correlation between leptin and NE absolute values, and leptin and insulin variations was found ( r 0.359, P<0.034 and r=0.560, P<0.007, respectively). Exposure to HA induces a decrease in fasting serum leptin concentrations in men. These changes are not linked to symptoms of AMS but to hormonal and energy balance variations, suggesting that leptin is involved in the endocrine and metabolic adaptations occurring during HA exposure.

Renal function may be compromised by extrahepatic cholestasis. In this context, the nephrotoxic role of bile salts is well known. Recently, however, it has been claimed that other factors, such as lipid peroxides, are involved. We therefore created bile duct ligation in 40 Sprague-Dawley rats. During the follow-up (from 1 to 28 days), significant variations were found in liver histological parameters, but not in renal morphology. Fourteen days after ligation, significant increases were found in serum and urinary thiobarbituric-acid-reactive species and phospholipase A₂ (indirect indices of lipid peroxidation), whereas 8-10 days after ligation, a significant decrease was observed in erythrocytic and hepatic GSH levels. The variations in urinary thiobarbituric-acid-reactive species and in phospholipase A₂ were not correlated with concomitant variations in the sera. Urinary lipid peroxides were directly correlated with the degree of liver morphological alterations and inversely with circulating GSH. Urinary outputs of lipid peroxides, phospholipase A₂ and N-acetyl-glucosaminidase were correlated with each other. These results suggest that there is an imbalance in the oxidative-antioxidant hepatic system in experimental extrahepatic cholestasis. The reduced bioavailability of blood GSH may alter the oxidative equilibrium in other organs, such as the kidney, triggering and favoring the lipoperoxidative cascade.

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