Scope: trans‐Resveratrol (RES) and/(or) its metabolites exert many effects in vivo. Our aim was to study the metabolism and tissue distribution of RES using the pig, a mammal physiologically close to humans.Methods and results: Forty‐seven tissues, organs and fluids were analyzed 6 h after intragastric RES administration (5.9 mg/kg body weight) using HPLC‐MS/MS. Twelve RES and seven dihydroresveratrol (DH‐RES) metabolites were detected. DH‐RES was the main metabolite in cecum, colon and rectum, whereas RES‐3‐O‐glucuronide was the most abundant one in fluids and organs. Approximately 74.5% of the total RES administered was recovered in the form of RES, DH‐RES and derived metabolites (65.1% along the gastrointestinal tract, 7.7% in urine, 1.2% in bile and 0.5% in organs). We report here, for the first time, the occurrence of RES ribosyl‐sulfate derivative, DH‐RES diglucuronide, DH‐RES sulfoglucuronide and DH‐RES disulfate as well as the metabolic profile of RES and DH‐RES in the aorta, lymph, lymph node, ovaries, uterus, cerebellum, pancreas, urinary bladder tissue, fat and muscle.Conclusion: This study contributes to the clarification of the metabolism and tissue distribution of RES and could help to further understand the mechanisms underlying its effects.

The effect of lipophilization of the antioxidant efficiency of hydroxytyrosol on fish oil enriched systems was studied. Hydroxytyrosol fatty acid esters with increasing size of the alkyl chain and different lipophilicity were tested in bulk fish oils and fish oil-in-water emulsions. Results showed a significant antioxidant activity of hydroxytyrosol esters in both systems especially in emulsions. The introduction of a lipophilic chain decreased the antioxidant effectiveness of hydroxytyrosol in homogeneous systems as fish oils. In emulsion systems, the presence of a short-medium lipophilic chain (acetate, butyrate or octanoate) improved the antioxidant efficiency of hydroxytyrosol favoring the physical location of the antioxidant in the interface, but longer alkyl chain (laurate) maintained or even decreased their antioxidant activity. A maximum of antioxidant efficiency seems to appear when the chain length of the hydroxytyrosol derivative is that of eight carbons which is probably associated with a preferential location of the diorthophenolic moiety in the right geometry. These results are of high importance for the optimum design of effective antioxidants for omega 3 enriched foods, which are very susceptible to suffer oxidation and, then, rancidity.

Our group has recently observed a nonlinear tendency in antioxidant capacity of different hydroxytyrosol fatty acid esters in fish oil-in-water emulsions, where a maximum of antioxidant efficiency appeared for hydroxytyrosol octanoate. These results appear to disagree with the antioxidant polar paradox. Because the physical location of the antioxidants in an oil-water interface has been postulated as an important factor in explaining this behavior, we have prepared a series of tyrosol and hydroxytyrosol fatty acid esters with different chain length and studied their surface-active properties in water, because these physicochemical parameters could be directly related to the preferential placement at the interface. We have found that tyrosol and hydroxytyrosol fatty acid esters are relevant surfactants when the right hydrophilic-lipophilic balance (HLB) is attained and, in some cases, as efficient as emulsifiers commonly used in industry, such as Brij 30 or Tween 20. Moreover, a nonlinear dependency of surfactant effectiveness is observed with the increase in chain length of the lipophilic antioxidants. This tendency seems to fit quite well with the reported antioxidant activity in emulsions, and the best antioxidant of the series (hydroxytyrosol octanoate) is also a very effective surfactant. This potential explanation of the nonlinear hypothesis will help in the rational design of antioxidants used in oil-in-water emulsions.

There is no pharmaceutical or definitive surgical cure for inflammatory bowel diseases (IBDs). The naturally occurring polyphenol resveratrol exerts anti-inflammatory properties. However, its rapid metabolism diminishes its effectiveness in the colon. The design of prodrugs to targeting active molecules to the colon provides an opportunity for therapy of IBDs. Herein we explore the efficacy of different resveratrol prodrugs and pro-prodrugs to ameliorate colon inflammation in the murine dextran sulfate sodium (DSS) model. Mice fed with a very low dose (equivalent to 10 mg for a 70 kg-person) of either resveratrol-3-O-(6'-O-butanoyl)-β-D-glucopyranoside (6) or resveratrol-3-O-(6'-O-octanoyl)-β-D-glucopyranoside (7) did not develop colitis symptoms and improved 6-fold the disease activity index (DAI) compared to resveratrol. Our results indicate that these pro-prodrugs exerted a dual effect: (1) they prevented the rapid metabolism of resveratrol and delivered higher quantities of resveratrol to the colon and (2) they reduced mucosal barrier imbalance and prevented diarrhea, which consequently facilitated the action of the delivered resveratrol in the colon mucosa.

Six synthetic heparin-like oligosaccharides have been used to investigate the effect of the oligosaccharide sulfation pattern on the stimulation of acidic fibroblast growth factor (FGF-1) induced mitogenesis signaling and the biological significance of FGF-1 trans dimerization in the FGF-1 activation process. It has been found that some molecules with a sulfation pattern that does not contain the internal trisaccharide motif, which has been proposed for high affinity for FGF-1, stimulate FGF-1 more efficiently than those with the structure of the regular region of heparin. In contrast to regular region oligosaccharides, in which the sulfate groups are distributed on both sides of their helical three-dimensional structures, the molecules containing this particular sulfation pattern display the sulfate groups only on one side of the helix. These results and the fact that these oligosaccharides do not promote FGF-1 dimerization according to sedimentation-equilibrium analysis, confirm the importance of negative-charge distribution in the activation process and strongly suggest that FGF dimerization is not a general and absolute requirement for biological activity.

The aim of this study was to verify the validity of a new progressive distance and fixed time test (Carminatti's test [TCAR]) in estimating the main physiological indices of aerobic fitness in team-sport players. Thirty professional national level team-sport players (n = 12 futsal players and 18 soccer players) volunteered to participate in this study. The subjects performed the TCAR and a laboratory incremental treadmill test (ITT). The TCAR required subjects to complete repeated sets of 5 × 12-second shuttle-running bouts at progressive speed until volitional exhaustion. Each 12-second bout and series were separated by a 6- and 90-second recovery periods, respectively. The initial distance was set at 15 m and was progressively increased by 1 m each set. The ITT commenced at a velocity of 9.0 km·h(-1) and was increased by 1.2 km·h(-1) each 3 minutes until volitional exhaustion. Peak TCAR running velocity resulted not significantly (p > 0.05) different from speed at VO2max (vVO2max) during ITT. Peak TCAR running velocity was significantly correlated (p < 0.01) with vVO2max (r = 0.55) and VO2max (r = 0.51). No significant differences were found (p > 0.05) among the mean values of velocity and heart rate at the anaerobic threshold, estimated in the TCAR test and measured in the ITT. In light of this study results, the TCAR can be considered as a viable field test to estimate aerobic power and capacity in team-sports players. The limited devices and space required by TCAR warrant consideration for those strength and conditioning professionals who deal with team sports.

SummaryProtein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic “lipid-altered” tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.

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