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Retinoic acid derivatives (retinoids) exert their pleiotropic effects on cell development through specific nuclear receptors, the retinoic acid receptors and retinoid X receptors. Despite recent progress in understanding the cellular and molecular mechanisms of retinoid activity, it is unknown which of the retinoid receptor pathways are involved in the specific processes of sebocyte growth and development. In this study, we investigated the roles of specific retinoid receptors in sebocyte growth and differentiation, by testing the effects of selective retinoic acid receptor and retinoid X receptor ligands at concentrations between 10-10 M and 10-6 M in a primary rat preputial cell monolayer culture system. Cell growth was determined by number of cells and colonies, and cell differentiation by analysis of lipid-forming colonies. All-trans retinoic acid and selective retinoic acid receptor agonists (CD271 = adapalene, an RAR-beta,gamma agonist; CD2043 = retinoic acid receptor pan-agonist; and CD336 = Am580, an RAR-alpha agonist) caused significant decreases in numbers of cells, colonies, and lipid-forming colonies, but with an exception at high doses of all-trans retinoic acid (10-6 M), with which only a small number of colonies grew but they became twice as differentiated as controls (42.2 +/- 4.0% vs 22.6 +/- 2.7%, mean +/- SEM, lipid-forming colonies, p < 0.01). Furthermore, the RAR-beta,gamma antagonist CD2665 antagonized the suppressive effects of all-trans retinoic acid, adapalene, and CD2043 on both cell growth and differentiation. In contrast, the retinoid X receptor agonist CD2809 increased cell growth slightly and lipid-forming colonies dramatically in a clear dose-related manner to a maximum of 73.7% +/- 6.7% at 10-6 M (p < 0. 001). Our data suggest that retinoic acid receptors and retinoid X receptors differ in their roles in sebocyte growth and differentiation: (i) retinoic acid receptors, especially the beta and/or gamma subtypes, mediate both the antiproliferative and antidifferentiative effects of retinoids; (ii) retinoid X receptors mediate prominent differentiative and weak proliferative effects; (iii) the antiproliferative and antidifferentiative effects of all-trans retinoic acid are probably mediated by retinoic acid receptors, whereas its differentiative effect at high dose may be mediated by retinoid X receptors via all-trans retinoic acid metabolism to 9-cis retinoic acid, the natural ligand of retinoid X receptors.
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PMID:The role of specific retinoid receptors in sebocyte growth and differentiation in culture. 1065 97

Lycopene from fresh and unprocessed tomatoes is poorly absorbed by humans. Absorption of lycopene is higher from processed foods such as tomato paste and tomato juice heated in oil. The aim of the present study was to develop a food-grade lycopene formulation that is bioavailable in humans. A formulation of lycopene named "lactolycopene" has been designed in which lycopene is entrapped with whey proteins. Healthy subjects (n = 33; 13 men and 20 women) participated and were allocated randomly to one of the three treatment groups. After a 3-wk deprivation of dietary lycopene, subjects ingested 25 mg lycopene/d for 8 wk from lactolycopene, tomato paste (positive control) or a placebo of whey proteins while consuming their self-selected diets. Plasma lycopene concentrations reached a maximum after 2 wk of supplementation in both lycopene-treated groups and then a plateau was maintained until the end of the treatment. Increases in plasma lycopene at wk 8 were not different between supplemented groups (mean +/- SEM): 0.58 +/- 0.13 micromol/L with lactolycopene and 0.47 plus minus 0.07 micromol/L with tomato paste, although they were different from the control (P < 0.001). Similar time-concentration curves of lycopene incorporation were observed in buccal mucosa cells. Although lycopene was present mainly as all-trans isomers (>90%) in both lycopene supplements, plasma lycopene enrichment consisted of 40% as all-trans and 60% as cis isomers. The precursor of lycopene, phytofluene, was better absorbed than lycopene itself. The lactolycopene formulation and tomato paste exhibited similar lycopene bioavailability in plasma and buccal mucosa cells in humans.
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PMID:A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste. 1188 May 63

The consumption of tomato products is associated with a reduced risk of cardiovascular disease and several cancers. It is hypothesized that lycopene, the major carotenoid in tomato products, may mediate this relationship. We designed a study to examine changes in plasma and buccal mucosal cell (BMC) lycopene concentrations in healthy adults consuming standard daily servings of processed tomato products: spaghetti sauce, tomato soup, or vegetable juice. Thirty-six healthy subjects consumed a lycopene-free diet for 2 wk and were then assigned to one of three (n = 12) intervention groups consuming daily, single servings of sauce (21 mg lycopene per (1/2) cup), soup (12 mg lycopene per 1 cup), or juice (17 mg lycopene per 8 oz) for 4 wk. Fasting blood and BMC samples were evaluated by high-performance liquid chromatography analysis for carotenoids and lycopene isomers. Total plasma lycopene concentrations (Mean +/- SEM) decreased from 1.05 +/- 0.07 to 0.54 +/- 0.05 micromol/l (49%, P < 0.0001) during the 2-wk washout period. Following intervention, plasma lycopene concentrations increased significantly for those consuming sauce, soup, and juice (compared with washout baseline) to 2.08 (192%, P < 0.0001), 0.91 (122%, P < 0.0001), and 0.99 (92%, P < 0.0001) micromol/l, respectively. Plasma isomer concentrations show a 61:39 ratio of cis:all-trans at the start of the study. During the 2-wk washout the decrease in plasma all-trans-lycopene was greater than that for pooled cis isomers (70:30 cis:trans ratio, P < 0.001). After 2 wk of dietary intervention isomer ratios returned to those observed at the start of the study. Total BMC lycopene concentrations did not significantly change during the brief washout. During the 4-wk intervention period, BMC total lycopene concentrations increased (P < 0.005) by 165, 42, and 48% nmol/mg protein for those consuming sauce, soup, and juice, respectively. This study demonstrates that plasma lycopene decreases by 50% after approximately 2 wk on a lycopene-free diet with a decrease in the ratio of all-trans compared with cis isomers. Single, daily servings of processed tomato products significantly increase blood and BMC lycopene for 2 wk. Additional studies of lycopene bioavailability, isomerization, metabolism, and bioactivity will provide greater insight into the potential health benefits suggested by epidemiological studies and laboratory investigations.
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PMID:Changes in plasma and oral mucosal lycopene isomer concentrations in healthy adults consuming standard servings of processed tomato products. 1476 37

Polystyrene/high-density polyethylene (PS/HDPE) blends were synthesized by melt blending in a single screw extruder. Co-continuity measurements using solvent extraction and scanning electron (SEM) micrographs showed that co-continuity was obtained around 35% PS. Thermal analyses measurements revealed a reduction in crystallinity of the HDPE phase around the co-continuous composition. Raman analyses across the entire composition range of these blends showed an increase in the normalized integral intensities of the 1128 cm(-1) and 1061 cm(-1) stretching vibrations of the HDPE molecules. The presence of all-trans HDPE chains that are not packed into an orthorhombic structure is used to explain the simultaneous occurrence of reduced crystallinity and increased intensity of all-trans HDPE stretch vibrations.
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PMID:Insight into the molecular arrangement of high-density polyethylene polymer chains in blends of polystyrene/highdensity polyethylene from differential scanning calorimetry and Raman techniques. 1675 98

Peripheral arterial disease is a leading cause of morbidity and mortality. The most commonly utilized prosthetic material for peripheral bypass grafting is expanded polytetrafluoroethylene (ePTFE) yet it continues to exhibit poor performance from restenosis due to neointimal hyperplasia, especially in femoral distal bypass procedures. Recently, we demonstrated that periadventitial delivery of all-trans retinoic acid (atRA) immobilized throughout porous poly(1,8 octamethylene citrate) (POC) membranes inhibited neointimal formation in a rat arterial injury model. Thus, the objective of this study was to investigate whether atRA immobilized throughout the lumen of ePTFE vascular grafts would inhibit intimal formation following arterial bypass grafting. Utilizing standard ePTFE, two types of atRA-containing ePTFE vascular grafts were fabricated and evaluated: grafts whereby all-trans retinoic acid was directly immobilized on ePTFE (atRA-ePTFE) and grafts where all-trans retinoic acid was immobilized onto ePTFE grafts coated with POC (atRA-POC-ePTFE). All grafts were characterized by SEM, HPLC, and FTIR and physical characteristics were evaluated in vitro. Modification of these grafts, did not significantly alter their physical characteristics or biocompatibility, and resulted in inhibition of intimal formation in a rat aortic bypass model, with atRA-POC-ePTFE inhibiting intimal formation at both the proximal and distal graft sections. In addition, treatment with atRA-POC-ePTFE resulted in increased graft endothelialization and decreased inflammation when compared to the other treatment groups. This work further confirms the biocompatibility and efficacy of locally delivered atRA to inhibit intimal formation in a bypass setting. Thus, atRA-POC-ePTFE grafts have the potential to improve patency rates in small diameter bypass grafts and warrant further investigation.
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PMID:Inhibiting intimal hyperplasia in prosthetic vascular grafts via immobilized all-trans retinoic acid. 2939 Dec 31


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