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We report a 31-year-old woman with sickle beta thalassemia zero who presented at 21 weeks gestational age with multiple bilateral pulmonary emboli and no hemodynamic instability. Acquired antithrombin deficiency was suspected due to a refractory response to therapeutic anticoagulation with enoxaparin, unfractionated heparin, and fondaparinux, and a reduced antithrombin antigen level. At 26 4/7 weeks, she developed signs concerning for increased pulmonary clot burden. To avoid the use of alternative anticoagulants that may cross the placenta and impact the fetus, a planned cesarean delivery was performed without complication at 27 weeks gestation. Both mother and child experienced successful long-term outcomes.

Cellular uptake of various carotenoids is not well understood. Recent investigations indicate that the Class B “scavenger receptor” SR‐B1 may govern cellular uptake of b‐carotene, lutein and vitamin E. To determine whether other lipoprotein (scavenger) receptors participate in carotenoid uptake in vivo, we examined mouse strains in which the genes for specific receptors (LDL Receptor [LDLR], SR‐A, CD36) were deleted by homologous recombination. METHODS: Male mice were housed in metabolic cages and fed lycopene‐enriched (0.25 g/kg chow) or standard diets for 30 days. Four genotypes (n=12 per group) were studied: wild type, LDLR−/−, SR‐A−/− and CD36−/−. Food intake and body weight were recorded every second day. After the feeding period, plasma and tissue samples collected. Sample extracts were prepared and lycopene measured by HPLC‐UV was normalized to protein content. RESULTS: Liver lycopene accumulation (ng lycopene/g tissue) was significantly reduced in SR‐A−/−, LDLR−/− and CD36−/− mice by 85%, 67% and ~30%, respectively, compared to wild type (p<0.001). Plasma lycopene concentrations were decreased by ~50% in SR‐A−/− mice (p<0.001) but were increased by 180% in LDLR−/− mice (p<0.001). CD36−/− plasma lycopene did not significantly differ from that of wild type. Prostate gland lycopene uptake profiles were similar to the plasma lycopene results. CONCLUSIONS: In addition to SR‐B, several scavenger receptors (SR‐A, CD36 and LDLR), particularly SR‐A, are important mediators of tissue‐specific lycopene uptake in the mouse. These findings are potentially important for dietary enrichment strategies and treatment of disorders, e.g., atherosclerosis and carcinogenesis, where enhancing carotenoid uptake may reduce risk. (NIH HD42174, RR18728)

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Introduction: Retinoic acid (RA) is critical for mammalian reproduction, embryonic development, growth, epithelial differentiation, vision and the immune response. Various pro‐vitamin A and other carotenoids have less well described tissue‐specific functions. b‐Carotene 9′,10′‐monoxygenase (CMO2) is an alternative enzymatic pathway for metabolizing provitamin A carotenoids into RA and metabolizing the non‐provitamin A carotenoid, lycopene. Serum lycopene levels have been inversely associated with the risk of prostate cancer and cardiovascular disease. Our laboratory and others have suggested CMO2 is may be a key mediator of lycopene metabolism and activity. We hypothesize that this enzyme pathway may be important in tumor cell sensitivity to lycopene. The objectives of this study were: to characterize CMO2 gene expression in various human cell lines and tissues, and to determine the expression and identify the function of spliced form CMO2. Methods: Using RT‐PCR, we investigated CMO2 expression in human liver HepG2 cells. A spliced form of CMO2 which lacks exon 6,7,8 was identified. We cloned this spliced form and used Western‐blot analysis to confirm its protein expression. Results: We found CMO2 mRNA is expressed as different spliced forms in HepG2 cells. A spliced form which lacks 3 exons compared with the full length CMO2 was sequenced. The expression of this spliced form CMO2 was confirmed in several prostate cell lines. We cloned this splice variant as well as full length CMO2 in a bacterial expression vector as fusion protein. Protein expression was confirmed by Western‐blot. In an E Coli testing system, we demonstrated this splice valiant has trans‐dominant negative activity for CMO2 metabolism of lycopene. (NIH HD42174, RR18728).