PubMed Health⌕ Search

Biomedical subjects

R Re

Publications and source records attributed to R Re.

At least 19 recordsLinked to original sources

Distribution of lipid-soluble antioxidants in lipoproteins from healthy subjects. I. Correlation with plasma antioxidant levels and composition of lipoproteins.

The concentration of five lipid-soluble antioxidants (gamma- and alpha-tocopherol, lycopene, beta-carotene and ubiquinol-10) was measured in plasma and very low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) isolated from young healthy normo- cholesterolemic subjects. Alpha-tocopherol was the exclusive antioxidant whose plasma concentration significantly correlated with the absolute concentration of total cholesterol (r =0.541, P<0.001). No correlation was found between plasma concentration and lipoprotein content of alpha-tocopherol and ubiquinol-10, whereas it reached statistically significant values for gamma-tocopherol, lycopene and beta-carotene. The alpha-tocopherol content in VLDL and HDL, but not in LDL, was strictly associated with the relative abundance of cholesterol and phospholipids in the lipoprotein particles. Moreover, the difference between alpha-tocopherol concentration in VLDL and LDL appeared to be strictly related to the differences in cholesterol, phospholipids and triglycerides. The percent distribution of the total plasma pool of antioxidant in each lipoprotein class revealed that gamma- and alpha-tocopherol were roughly equally distributed in LDL and HDL. On the other hand, lycopene, beta-carotene and ubiquinol-10 were preferentially sequestered in LDL. Finally, the absolute and relative concentration of alpha-tocopherol, but not that of other antioxidants, in HDL exhibited a statistically significant correlation with plasma HDL/LDL cholesterol ratio. These findings indicate that: (i) plasma concentrations of major lipid-soluble antioxidants are not always predictive of their levels in lipoproteins and that, within individual lipoprotein classes, (ii) the lipid composition, metabolism and relative plasma concentration may significantly affect their abundance.

Adult↗

Distribution of lipid-soluble antioxidants in lipoproteins from healthy subjects. II. Effects of in vivo supplementation with alpha-tocopherol.

The effects of orally supplemented dl -alpha-tocopherol on the plasma concentration of lipid-soluble antioxidants and their distribution in very-low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) was investigated in a cohort of control normocholesterolemic adult subjects receiving 600 mg alpha-tocopherol daily for 2 weeks. This regimen did not modify the plasma lipid profile (total, LDL and HDL cholesterol and triglycerides) and chemical composition of VLDL, LDL and HDL. Plasma concentration of alpha-tocopherol increased from 19.44+/-4.77 to 38. 03+/-9.06 microm and this was associated with slight decrease in the concentration of gamma-tocopherol from 1.27+/-0.97 to 0.99+/-1.17 microm, without any significant changes of either lycopene and beta-carotene. Qualitatively similar changes were found in VLDL, LDL and HDL but the net increase of alpha-tocopherol in plasma did not correlate with the increase in alpha-tocopherol content in any of the lipoprotein types. Following supplementation, the percentage of total plasma alpha-tocopherol pool carried by VLDL increased from 20. 97+/-6.07% to 33.57+/-6.97%, whereas it decreased from 41.85+/-7.02% to 36.36+/-5.69% in the case of LDL and from 37.17+/-6.04% to 30.05+/-4.88% in the case of HDL. The absolute and relative enrichment of alpha-tocopherol in either VLDL and LDL did not exhibit any statistically relevant correlation with the chemical composition of these lipoproteins in the different subjects investigated. On the other hand, the amount of alpha-tocopherol enriching the HDL particles was inversely related to the relative abundance of protein (r =0.449;P<0.05) and directly to the phospholipid/protein ratio (r =0.480, P<0.05).

Adult↗

Antioxidant activity applying an improved ABTS radical cation decolorization assay.

A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.

Antioxidants↗

The nature of intracrine peptide hormone action.

Current theory holds that peptide hormone action results from hormone binding to cell-surface receptors, with the generation of intracellular second messengers. However, a growing body of evidence suggests that intracellular peptide hormone, either internalized or synthesized in situ, can exert physiologically relevant effects. These effects are diverse and poorly understood. I propose that such intracrine action can serve to modulate cellular function over time and thereby play a role in biological memory of various sorts, in the maintenance of hormonal responsiveness, and in cellular differentiation.

Cell Differentiation↗

Macromolecular carbonyls in human stratum corneum: a biomarker for environmental oxidant exposure?

The presence of stratum corneum carbonyls may serve as an intrinsic dosimeter for environmental oxidative damage to skin. To investigate the accumulation of carbonyls in human stratum corneum, skin was tape-stripped, then tapes were sequentially incubated with 2,4-dinitrophenyl hydrazine (DNPH), rat anti-DNP, mouse anti-rat IgG conjugated with alkaline phosphatase, p-nitrophenyl phosphate and absorbance (405 nm) measured and carbonyls estimated. Stratum corneum exposed in vitro to oxidants: hypochlorous acid (1, 10, 100 mM), ozone (0, 1, 5, 10 ppm for 2 h) or UV light (280-400 nm; 0, 4, 88, or 24 J/cm2) contained increased carbonyls. Furthermore, stratum corneum carbonyls were elevated in tanned compared with untanned sites: dorsal hand (0.43 +/- 0.06 nmol/cm2) vs. lower arm (0.32 +/- 0.04, mean +/- S.E.M., n = 11; P < 0.003) and lower back (0.26 +/- 0.02) vs. buttock (0.21 +/- 0.02; n = 6, P < 0.01) indicating in vivo oxidative damage.

Aldehydes↗

Antioxidant reactions of all-trans retinol in phospholipid bilayers: effect of oxygen partial pressure, radical fluxes, and retinol concentration.

Lipoperoxyl radical-scavenging activity of retinol in unilamellar soybean phosphatidylcholine liposomes was studied under a variety of conditions to appreciate to what extend retinol may be considered an effective antioxidant. Peroxidation, initiated by 2 mM 2,2'-azobis(amidino-propane)hydrochloride (AAPH), was carried out at 160 torr O2 or at 15 torr O2, in the absence or in the presence of 10 to 40 mM retinol. As evaluated by the length of the inhibition periods, t(inh), and by the ratio between the inhibition and propagation rate, R(inh)/R(p), the antioxidant activity of retinol was higher at 15 torr O2 than at 160 torr O2. The consumption rate of retinol was markedly faster at 160 torr O2 than at 15 torr O2 and increased with the increase of retinol concentration under both oxygen tensions. When liposome peroxidation was carried out under N2, retinol consumption was independent of retinol concentration. Peroxyl radicals oxidize retinol to 5,6-retinol epoxide. The ratio between 5,6-epoxide formed and the retinol consumed was markedly higher at 15 torr O2 than under air and decreased with the increased retinol concentrations. When butylated hydroxytoluene was included into the liposomal suspension, most of the consumed retinol was converted into 5,6-epoxide. Liposomes were incubated at 15 torr O2, in the presence of 0.5 to 10 mM AAPH. The antioxidant effectiveness of 40 mM retinol, as measured by the R(inh)/R(p) ratio, increased with the increase of the radical fluxes. The results suggest, besides radical trapping, that a major consumption of retinol during lipid oxidation occurs through self-oxidation reactions, which are concentration- and oxygen-dependent. A decreased self-oxidation makes retinol a better lipoperoxyl radical scavenger at low, rather than at high partial pressure of oxygen. However, when self-oxidation of retinol is prevented, only a minor fraction of the antioxidant is allowed to effectively act as a radical scavenger, suggesting that the radical-trapping reactions are rate-limiting for the antioxidant process. Peroxyl radical concentration, by shifting the route of the retinol activity toward radical scavenging, brings about an increasingly more efficient radical trapping. It is concluded that all-trans retinol behaves as a more effective antioxidant at low oxygen partial pressure, low retinol concentrations, and high radical flux.

Antioxidants↗

Comparing comorbid-illness indices assessing outcome variation: the case of prostatectomy.

OBJECTIVE: We investigated and compared the effects of three different comorbid indices on selection of procedure and outcome variation to determine which, if any, could be used for interpreting outcomes data. DESIGN: Retrospective cohort study. SETTING: Large multispecialty group practice. PATIENTS: Patients (aged 55-85 years) with residence in the United States who underwent a first-time prostatectomy for benign prostatic hyperplasia: 302 total; 253 transurethral procedures (TURF) versus 49 open procedures (OP). MEASUREMENTS AND MAIN RESULTS: The following indices were used to assess comorbid disease: Charison index (CI), index of coexistent disease (ICED), and Kaplan-Feinstein index (KFI). The main outcome measure was the five-year mortality rate. The unadjusted five-year mortality rates were 16% (40/ 253) for TURP and 4% (2/49) for OP; survival analysis revealed this difference to be marginally significant at the p = -05 level. In an effort to control for the effect of comorbidity, CI, ICED, and KFI were independently assessed: together with age, they each had similar effects in rendering the risk of death associated with procedure type insignificant. However, comorbidity, as derived with ICED (not CI or KFI), was identified as a confounding variable when assessing the five-year mortality rate after prostatectomy as ICED was associated with the procedure type (predictor variable) and the five-year mortality (outcome variable). CONCLUSION: Differences in the composition and scoring of comorbid indices may have important implications for interpreting outcomes data. Nevertheless, these results, together with those of previous studies, suggest that the reported increased mortality for patients undergoing TURP is probably due to case-mix differences.

Aged↗

Multilayer perceptrons to approximate complex valued functions.

In this paper the approximation capabilities of different structures of complex feedforward neural networks, reported in the literature, have been theoretically analyzed. In particular a new density theorem for Complex Multilayer Perceptrons with complex valued non-analytical sigmoidal activation functions has been proven. Such a result makes Multilayer Perceptrons with complex valued neurons universal interpolators of continuous complex valued functions. Moreover the approximation properties of superpositions of analytic activation functions have been investigated, proving that such combinations are not dense in the set of continuous complex valued functions. Several numerical examples have also been reported in order to show the advantages introduced by Complex Multilayer Perceptrons in terms of computational complexity with respect to the classical real MLP.

Neural Networks, Computer↗

Reciprocal protective effects of all-trans retinol and alpha-tocopherol during lipid peroxidation in retinal membranes.

Interactions between vitamin A and vitamin E in suppressing lipid peroxidation were observed in bovine retinal membrane preparations submitted to peroxidative injury by the water soluble azo initiator 2,2'-azobis(2-amidino-propane) hydrochloride (AAPH). Incorporation of 0.75 nmol mg prot(-1) all-trans retinol, an amount comparable with that of the endogenous alpha-tocopherol, significantly elongated the induction time preceding the release of TBA-reactive lipid peroxidation products, and reduced the consumption rate of the endogenous alpha-tocopherol. On the other hand, all-trans retinol was not able to induce any delay to the onset of lipid peroxidation when incorporated in membranes deprived of endogenous alpha-tocopherol by exposure to UV light, although TBARS produced within 60 min decreased slightly. Consumption of all-trans retinol during peroxidation was more rapid when all-trans retinol was incorporated in membranes deprived of alpha-tocopherol than in native membranes. These data suggest that reciprocal protective effects between vitamin A and vitamin E may strongly contribute to the defence of membranes against oxidative stress.

Amidines↗

Vitamin A preserves the cytotoxic activity of adriamycin while counteracting its peroxidative effects in human leukemic cells in vitro.

Previous results from our laboratory gave evidence that safe doses of vitamin A were very effective in protecting rats from adriamycin-induced oxidative stress and lethal cardiotoxicity (Tesoriere, L. et al. (1994) J. Pharmacol. Experim. Ther. 269, 430-436). This was an incentive also to evaluate whether or not vitamin A affected the antitumor activity of adriamycin. K562 human erythroleukemia cells were exposed to adriamycin or to adriamycin plus vitamin A. Presence of 2.5 to 15 microM all-trans retinol in the cell culture did not impair the cytotoxicity of adriamycin. Rather, an enhanced cell death was observed when cell colony was exposed to both compounds. Additional assays showed that all-trans retinol counteracted the lipoperoxide formation, assayed as malondialdehyde, induced in cell cultures by the redox cycling activity of adriamycin. These data strongly encourage a new therapeuthical approach with safe doses of vitamin A as an adjuvant in cancer chemotherapy.

Cell Line↗

Angiotensin and the regulation of cellular growth. Pathophysiologic implications for cardiovascular and noncardiovascular tissues.

Components of the renin-angiotensin system can be found in the vasculature, although in most cases it is unclear how much, if any, of this renin in the vasculature is locally synthesized. Over recent years, a variety of novel actions of angiotensin II have been delineated which suggest that in appropriate physiologic or pathologic circumstances vascular angiotensin II can play an important role in determining vascular structure. Moreover, angiotensin II may play a role in neoplastic growth of vascular and nonvascular tissues.

Angiotensin II↗

New approaches to the study of the cellular biology of the cardiovascular system.

Recent findings suggest that the local renin-angiotensin systems, locally generated catecholamines, and possibly other locally generated peptides interact in a complex fashion to regulate the cellular biology of the myocardium, the vascular wall, and other tissues. New evidence indicates that the components of the renin-angiotensin system are synthesized in cardiovascular tissues, that the synthesis of these components can be modulated by pharmacologic agents, and that angiotensin II, the effector protein of the renin system, appears to be capable of producing hypertrophy or hyperplasia in specific tissues. In addition, recent studies suggest the participation of enhanced proto-oncogene transcriptional activity in the development of hyperplasia and hypertrophy in cardiovascular tissue. Taken together, these data raise the possibility that angiotensin and perhaps other components of the renin system can be viewed as locally active growth factors capable of acting in a fashion similar to that associated with cytokines in other systems.

Animals↗

The myocardial intracellular renin-angiotensin system.

In recent years several tissues have been found to contain the components of the renin-angiotensin system. Locally synthesized renin could conceivably function in an endocrine, paracrine or autocrine manner. Isolated left ventricular cardiac myocytes of the rat were examined in the present study and renin and angiotensin II were detected in these cells. This observation suggests the existence of a functioning renin-angiotensin system in the heart and, more particularly, in the left ventricular cardiac myocyte. Additional evidence, derived from micrococcal nuclease and deoxyribonuclease I treatment of angiotensin II-exposed chromatin, suggests that angiotensin II could subserve an intracellular function in some of its cells of synthesis.

Animals↗

Effect of angiotensin II on RNA synthesis by isolated nuclei.

Peptide hormones are known to bind to cell surface receptors as the first step in the generation of their effects on target tissues. However, it remains uncertain whether internalized hormone might also play a role in the production of longterm or trophic effects of peptide hormones. Because the peptide hormone angiotensin II appears to be internalized by target cells, we studied the effect of this peptide on isolated hepatic nuclei. At both 5 X 10(-7)M and 5 X 10(-9)M, angiotensin II significantly increased RNA synthesis. This effect was not mimicked by Sar1-Ala8-angiotensin II (saralasin) or the unrelated nonapeptide teprotide.

Angiotensin II↗

A simplified radioimmunoassay for physiologically active angiotensin peptides [(1-8) octa- and (2-8) heptapeptides].

The availability of a sensitive and highly specific rabbit antiserum and the development of a peptide-extraction method employing glass beads permitted the evolution of a rapid reliable radioimmunoassay that measures the sum of the concentration of angiotensin II and its active metabolite, angiotensin III. At a dilution of 1:32,000 the antiserum is capable of measuring 1 fmol (1 pg) of angiotensin II. Cross reactivities of this antiserum, taking angiotensin II as 1.0, are: angiotensin III, 0.75; angiotensin-(3-8) hexapeptide, 0.11; angiotensin I, 0.006; angiotensin-(1-14) tetradecapeptide, 0.0001. The recovery of angiotensin II added to hormone-free plasma was 73 +/- 2% [mean +/- standard deviation (SD), n = 20]. When 0.9 ml of plasma was extracted, the minimal concentration of angiotensin II and III that could be quantified was 4 fmol/ml. When larger volumes of plasma were extracted, sensitivity was enhanced. Plasma blanks were zero. Intra-assay variability was 7.6% SD and interassay variability was 11.7% SD. Angiotensin II and III concentration in venous plasma of normal volunteers on an ad libitum diet was 15 +/- 8 fmol/ml (mean +/- SD, range less than 4 to 35 fmol/ml). The plasma of a patient with primary aldosteronism had an unmeasurable value (less than 4 fmol/ml). Posture, converting enzyme inhibition, and renal artery stenosis resulted in expected changes of angiotensin concentration.

Angiotensin II↗