The total content and profile of bile salts and phospholipids are reported for several mammalian biles. Rabbit and guinea-pig biles are characterized by high proportions of conjugated dihydroxy bile salts with respect to trihydroxy bile salts, but contain relatively little phospholipid. Both rabbit and guinea-pig biles exhibit little evidence of hepatic cell damage, even though they are able to cause membrane damage (as evidenced by lysis of human erythrocytes) at low (2--3 mM) concentrations of bile salts; this lytic behaviour is also a property of their predominant bile salts. Addition of phosphatidylcholine to the bile or bile salt is able to decrease the lytic behaviour. Perhaps the most significant observation is that these biles, and their predominant bile salts, are dramatically less lytic towards sheep erythrocytes, indicating that some factor(s) in membrane composition and structure may partly explain the resistance of membranes of the biliary tract to the presence of high concentrations of potentially membrane-damaging bile salts.

Garlic has been widely reported to protect against cardiovascular disease by reducing serum cholesterol concentrations and blood pressure and by inhibiting platelet aggregation. However, most of these studies have been performed in hypercholesterolemic subjects or in animal models. We performed a 13-wk study in normolipidemic subjects who ingested 5 mL of aged garlic extract (AGE, Kyolic) per day. Blood was drawn from these subjects at the beginning and end of the study. Aggregation of platelet-rich plasma was induced by ADP; full lipid profiles and liver function tests were determined on serum, and plasma concentrations of eicosanoids were also measured. Dietary supplementation with AGE significantly inhibited both the total percentage and initial rate of platelet aggregation at concentrations of ADP up to 10 mol/L. The K M for ADP-induced aggregation were approximately doubled after supplementation with AGE, whereas the maximum rate of aggregation was unaffected. No significant changes in plasma thromboxane B 2 and 6-ketoprostaglandin F 1␣ concentrations or serum lipid profiles were observed. We conclude that AGE, when taken as a dietary supplement by normolipidemic subjects, may be beneficial in protecting against cardiovascular disease as a result of inhibiting platelet aggregation. J. Nutr. 130: 2662-2665, 2000.Garlic (Allium sativum) has been used for many centuries, as both a flavoring and a folk medicine. At present, the potential therapeutic and health-promoting effects of garlic are attracting considerable interest (Agarwal 1996). For example, garlic has been shown to be antitumorigenic (Kyo et al. 1998, Milner 1996 and to inhibit a variety of chemically induced cancers, including those of the breast (Schaffer et al. 1997) and skin (Perchellet et al. 1990). Garlic and some of its constituents have also been shown to be protective against acetaminophen (Wang et al. 1996) and bromobenzene toxicities (Wang et al. 1999).By far the most widely studied and reported health-promoting effect of garlic is cardioprotection. Cardiovascular disease is multifactorial, and garlic appears to exert its beneficial effects at several different sites in the pathogenesis of the disease. Several reports have claimed that garlic lowers plasma cholesterol concentrations, particularly those of LDL (Neil et al. 1996, Steiner et al. 1996. More recently, an aged garlic extract was shown to inhibit directly the formation of atherosclerotic plaques in de-endothelialized carotid arteries in rabbits fed a diet supplemented with 1% cholesterol (Efendy et al. 1997). The oxidative modification of LDL is now recognized as an important process in the development of atherosclerosis, and garlic has been shown to inhibit Cu 2ϩ -induced oxidation of LDL in vitro and to protect cultured vascular endothelial cells from injury induced by oxidized LDL (Ide and Lau 1997). In addition, Munday et al. (1999) reported that ingestion of an aged garlic extract (AGE), 3 but not raw garlic, inhibits the oxidation of subsequently isolated LDL. F...

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A variety of achiral conformationally restricted spirocyclic piperidines have been prepared in an attempt to investigate the functional role of the central sigma recognition site. All the compounds possessed a lipophilic N-substituent incorporating either a tetralin, indan, or benzocycloheptane skeleton. Their in vitro affinity at the sigma site was assessed in radioligand displacement experiments with guinea pig cerebellum homogenates using the sigma-specific radioligand [3H]-N,N'-di-o-tolylguanidine ([3H]-DTG, [3H]-6). A study of the structure-activity relationships identified the N-butyl and N-dimethylallyl substituents as the optimum groups for high affinity and selectivity at the sigma site (e.g., 3,4-dihydro-1'-(3-methylbut-2-enyl)spiro[1H-indene-1,4'-piperidine ] (48), pIC50 = 8.9 vs [3H]-6 and greater than 10,000-fold selective over the dopamine D2 receptor). Such compounds are amongst the highest affinity sigma ligands reported to date, with excellent selectivity over the dopamine D2 receptor, and may serve as a useful tool for exploring the physiological role of the sigma site.

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