JTT-130, a Microsomal Triglyceride Transfer Protein (MTP) Inhibitor Lowers Plasma Triglycerides and LDL Cholesterol Concentrations without Increasing Hepatic Triglycerides in Guinea Pigs

BACKGROUND: Microsomal transfer protein inhibitors (MTPi) have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG). However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. METHODS: Male guinea pigs (n = 10 per group) were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control), 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. RESULTS: Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P < 0.05). Atorvastatin had the most pronounced hypolipidemic effects with a 35% reduction in LDL cholesterol and 40% reduction in TG. JTT-130 did not induce hepatic lipid accumulation compared to controls. Cholesteryl ester transfer protein (CETP) activity was reduced in a dose dependent manner by increasing doses of MTPi and guinea pigs treated with atorvastatin had the lowest CETP activity (P < 0.01). In addition the number of molecules of cholesteryl ester in LDL and LDL diameter were lower in guinea pigs treated with atorvastatin. In contrast, hepatic enzymes involved in maintaining cholesterol homeostasis were not affected by drug treatment. CONCLUSION: These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

Extractable Soil Phosphorus Concentrations and Creeping Bentgrass Response on Sand Greens

Few studies have directly related turfgrass growth and quality responses to extractable soil P concentrations in sand greens. A 3-yr field experiment was conducted on a sand-based putting green to determine creeping bentgrass (Agrostis stolonifera L.) growth and quality responses to extractable soil P. Extractable soil P concentrations were obtained by using the modified-Morgan, Mehlich-1, and Bray-1 extractants. Critical extractable P concentrations (above which there is a low probability of response to increasing soil P concentrations) for shoot counts, thatch thickness, relative clipping yields, quality ratings, P deficiency ratings, tissue P concentrations, and root weights were determined using Cate-Nelson (CN) and quadratic response and plateau (QRP) models. Both models fit the data relatively well in most cases (R2 values from 0.12 to 0.89), and critical concentrations for the QRP models were always greater than the CN models. Critical extractable P concentrations were lowest for the modified-Morgan extractant (1.4 to 12.0 mg kg(-1)) and greatest for the Mehlich-1 extractant (14.1 to 63.6 mg kg(-1)). Application of estimated critical extractable P concentrations in this study could be used to substantiate observed responses or explain lack of responses in other previously reported creeping bentgrass P studies. We found better model fits with modified-Morgan extractable P for bentgrass quality ratings, deficiency ratings, and tissue P concentrations than with P extracted by the Mehlich or Bray methods. This suggests that the modified-Morgan extractant may have advantages over stronger-acid extractants when used on sand-based media. The results can be used to revise or update existing P fertilization recommendations for bent-grass grown on sand-based media.