There is now a general consensus that the intestinal absorption of water-insoluble, dietary lipids is protein-mediated, but the assignment of protein(s) to this function is still a matter of debate. To address this issue, we measured beta-carotene and cholesterol absorption in wild-type and SR-BI knockout mice and the uptake of these lipids in vitro using brush border membrane (BBM) vesicles. From the comparison of the in vivo and in vitro results we conclude that both BBM-resident class B scavenger receptors, SR-BI and CD36, can facilitate the absorption of beta-carotene and cholesterol. SR-BI is essential for beta-carotene absorption, at least in mice on a high fat diet. This is due to the fact that the absorption of beta-carotene is restricted to the duodenum and SR-BI is the predominant receptor in the mouse duodenum. In contrast, SR-BI may be involved but is not essential for cholesterol absorption in the small intestine. The question of whether SR-BI contributes to cholesterol absorption in vivo is still unresolved. Transfection of COS-7 cells with SR-BI or CD36 confers on these cells lipid uptake properties closely resembling those of enterocytes and BBM vesicles. Both scavenger receptors facilitate the uptake of dietary lipids such as beta-carotene, free and esterified cholesterol, phospholipids, and fatty acids into COS-7 cells. This lipid uptake is effected from three different lipid donor particles: mixed bile salt micelles, phospholipid small unilamellar vesicles, and trioleoylglycerol emulsions which are all likely to be present in the small intestine. Ezetimibe, a representative of a new class of drugs that inhibit intestinal cholesterol absorption, blocks SR-BI- and CD36-facilitated uptake of cholesterol into COS-7 cells.

Here we show that scavenger receptor class B type I is present in the small-intestine brush border membrane where it facilitates the uptake of dietary cholesterol from either bile salt micelles or phospholipid vesicles. This receptor can also function as a port for several additional classes of lipids, including cholesteryl esters, triacylglycerols, and phospholipids. It is the first receptor demonstrated to be involved in the absorption of dietary lipids in the intestine. In liver and steroidogenic tissues, the physiological ligand of this receptor is high-density lipoprotein. We show that binding of high-density lipoprotein and apolipoprotein A-I to the brush border membrane-resident receptor inhibits uptake of cholesterol (sterol) into the brush border membrane from lipid donor particles. This finding lends further support to the conclusion that scavenger receptor BI catalyzes intestinal cholesterol uptake. Our findings suggest new therapeutic approaches for limiting the absorption of dietary cholesterol and reducing hypercholesterolemia and the risk of atherosclerosis.

This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration. In a randomized, double-blinded, placebo-controlled study, 90 premenopausal women presenting with fatigue, serum ferritin < 50 ng/mL, and hemoglobin > 120 g/L were randomized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo. Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks. Median fatigue at baseline was 4.5 (on a 0-10 scale). Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group (P ‫؍‬ .07). Efficacy of iron was bound to depleted iron stores: In patients with baseline serum ferritin < 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P ‫؍‬ .005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P ‫؍‬ .03). Drug-associated adverse events were observed in 21% of iron-treated patients and in 7% of placebo-treated patients (P ‫؍‬ .05); none of these events was serious. Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women with a good safety and tolerability profile. The efficacy of intravenous iron was bound to a serum ferritin concentration < 15 ng/mL. Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 3450. Disclosures This study was funded by Vifor Pharma (Villars-sur-Glâne, Switzerland). The sponsor of the study was involved in the trial design and was responsible for data collection and storage. The authors had full access to all data and were responsible for the analysis and interpretation of the data presented in this publication. Christian Breymann is a consulting expert for Vifor Pharma in the field of obstetrics and gynecology. The remaining authors, the Associate Editor Martin S. Tallman, and the CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interests. Learning objectives Upon completion of th...

Our objective was to study the effect of metal-induced artifacts on the accuracy of the CT-based anatomic map as a prerequisite for attenuation correction of the positron emission tomography (PET) emission data. Twenty-seven oncology patients with dental metalwork were enrolled in the present study. Data acquisition was performed on a PET/CT in-line system (Discovery LS, GE Medical Systems, Milwaukee, Wis.). Attenuation correction of emission data was done twice, using an 80-mA CT scan (PET(CT80)) and a (68)Ge transmission scan (PET(68Ge)). Average count in kBq/cc was measured in regions with and without artifacts and compared for PET(CT80) and PET(68Ge). Data analysis of region of interests (ROIs) revealed that the ratio (ROIs PET(CT80)/ROIs PET(68Ge)) and the difference (ROIs PET(CT80) minus ROIs PET(68Ge)) had a higher mean of values in regions with artifacts than in regions without artifacts (1.2+/-0.17 vs 1.06+/-0.06 and 0.68+/-0.67 vs 0.15+/-0.17 kBq/cc, respectively). For most of the studied artifactual ROIs, the PET(CT80) values were higher than those of the PET(68Ge). Attenuation correction of PET emission data using an artifactual CT map yields false values in regions nearby artifacts caused by dental metalwork. This may falsely estimate PET quantitative studies and may disturb the visual interpretation of PET scan.