Objective-Alterations of the chemokine receptor CX3CR1 gene were associated with a reduced risk of myocardial infarction in human and limited atherosclerosis in mice. In this study, we addressed whether CX3CR1 antagonists are potential therapeutic tools to limit acute and chronic inflammatory processes in atherosclerosis. Approach and Results-Treatment with F1, an amino terminus-modified CX3CR1 ligand endowed with CX3CR1 antagonist activity, reduced the extent of atherosclerotic lesions in both Apoe −/− and Ldlr −/− proatherogenic mouse models. Macrophage accumulation in the aortic sinus was reduced in F1-treated Apoe −/− mice but the macrophage density of the lesions was similar in F1-treated and control mice. Both in vitro and in vivo F1 treatment reduced CX3CR1-dependent inflammatory monocyte adhesion, potentially limiting their recruitment. In addition, F1-treated Apoe −/− mice displayed reduced numbers of blood inflammatory monocytes, whereas resident monocyte numbers remained unchanged. Both in vitro and in vivo F1 treatment reduced CX3CR1-dependent inflammatory monocyte survival. Finally, F1 treatment of Apoe −/− mice with advanced atherosclerosis led to smaller lesions than untreated mice but without reverting to the initial phenotype. Conclusions-The

We studied the effects of acute ingestion of intoxicating doses of alcohol on jejunal motility in six male volunteers ages 24-45 who had two 24-hr ambulatory manometries, one week apart, that each included three standardized meals with either red wine (0.6 g of alcohol/kg) or dealcoholized wine. Breath alcohol was measured at regular intervals for 3 hr following alcohol. The results show that the MMC cycle was significantly (P < 0.01) shorter during the night than during the day in the "nonalcohol" group but not in the "alcohol" group and that the amplitude of contractions was higher during the night than the day in the alcohol group (P < 0.01). All meals interrupted the MMC and induced a fed pattern. After the 300-kcal liquid meal, the duration of the fed pattern was shorter (P < 0.01), with a lower motility index (P < 0.01) and fewer contractions (P < 0.01), than following the two 600-kcal meals. The number of clustered contractions occurring in the postprandial period was lower in the alcohol group than in the nonalcohol group. After the three alcohol doses, a breath alcohol peak was reached in 20-60 min, and in all subjects, breath alcohol fell below 22 micrograms/100 ml after the third hour. This study showed that alcohol had only minor effects on postprandial contractile activity but abolished the circadian variation of the MMC normally seen in healthy subjects. The fact that breath alcohol was low by the time of onset of sleep, suggests that the effects on the MMC may be mediated through central rather than local mechanisms.

SUMMARYBackground: The administration of exogenous neurotensin can reduce the lower oesophageal sphincter pressure, but it is unclear whether this effect is pharmacological or physiological. Aim: A specific neurotensin receptor antagonist (SR 48692) was used to assess the effect of endogenous neurotensin on lower oesophageal sphincter function. Methods: Twenty-four healthy male subjects were included in a double-blind, placebo-controlled, randomized, cross-over study designed to determine the effects of two single doses (90 and 300 mg, preceded by a loading dose) of SR 48692 on the resting lower oesophageal sphincter pressure, transient lower oesophageal sphincter relaxations, primary oesophageal peristalsis and oesophageal acid exposure. Oesophageal