PubMed Health⌕ Search

Biomedical subjects

D Caruso

Publications and source records attributed to D Caruso.

At least 19 recordsLinked to original sources
PubMed2001

Multiple lipomas linked to an RB1 gene mutation in a large pedigree with low penetrance retinoblastoma.

Hereditary predisposition to lipomas is observed in familial multiple lipomatosis (OMIM 151900) and benign cervical lipomatosis (OMIM 151800) and can also be associated with mutations in the MEN1 and PTEN genes (OMIM 131100 and 153480, respectively). In addition, a recent report indicates that a few patients with hereditary retinoblastoma also have lipomas. Here we report on an extended family segregating a splice site mutation in the RB1 gene. Almost all adult carriers of this mutation had multiple lipomas while penetrance for retinoblastoma was incomplete. In an unrelated pedigree, which was reported previously, the identical mutation was only associated with low-penetrance retinoblastoma but not lipomas. Our data indicate that lipoma predisposition in hereditary retinoblastoma is not associated with specific RB1 gene mutations but is influenced by modifying factors linked to this gene.

Base Sequence↗
PubMed2001

Urinary excretion of olive oil phenols and their metabolites in humans.

We have recently demonstrated, in humans, the bioavailability of hydroxytyrosol (3,4-dihydroxyphenylethanol; HT), one of the major antioxidant components of virgin olive oil. In particular, we reported that this compound is present in lipoproteins involved in atherosclerotic processes and is excreted in the urine mainly as glucuronide-conjugate. The aim of the present study was to elucidate, in humans, the metabolic fate of HT after ingestion of virgin olive oil. After administration of virgin olive oil, 24-hour urine collections of healthy volunteers were prepared for gas chromatography-mass spectrometry analyses in order to identify and quantify HT and its metabolites homovanillic alcohol (HVA1c) and homovanillic acid (HVA). The results indicate that this compound undergoes the action of catechol-O-methyl transferase (COMT), enzymes involved in the catecholamine catabolism, resulting in an enhanced excretion of HVA1c. We also found a significant increase of HVA, indicating an oxidation of the ethanolic residue of HT and/or of HVA1c in humans. The excretion of both metabolites significantly correlated with the dose of administered HT.

Biological Availability↗
PubMed2001

Hydroxytyrosol, as a component of olive mill waste water, is dose- dependently absorbed and increases the antioxidant capacity of rat plasma.

Hydroxytyrosol is the most potent phenolic antioxidant of olive oil and olive mill waste water (OMWW) and its biological activities have stimulated research on its potential role in cardiovascular protection. However, evidence of the absorption of OMWW phenolics and on their possible in vivo activity has, until now, never been provided. Three groups male Sprague-Dawley rats were administered 1, 5, or 10 mg/Kg of the OMWW extract, respectively, providing 41.4, 207, and 414 microg/Kg of hydroxytyrosol, respectively. Urine was collected for 24 h and the urinary levels of hydroxytyrosol were quantified by mass spectrometry. Hydroxytyrosol was dose-dependently (R(2) = 0.95) absorbed and excreted in the urines mostly as a glucuronide conjugate. Further, the administration of an hydroxytyrosol-rich OMWW extract (10 mg/kg) to the rats was also associated with an increase of their plasma antioxidant capacity. Future experiments will eventually further clarify its metabolic fate and its in vivo actions.

Animals↗
PubMed2000

Olive oils rich in natural catecholic phenols decrease isoprostane excretion in humans.

This study was undertaken to evaluate, in humans, the antioxidant activity of olive oil phenolics, namely hydroxytyrosol and oleuropein aglycone that share an orthodiphenolic (catecholic) structure. Human volunteers were administered olive oil samples containing increasing amounts of an olive oil phenolic extract that was characterized by gas-chromatography/mass spectrometry. The administration of phenol-rich oils was dose-dependently associated with a decreased urinary excretion of 8-iso-PGF(2alpha), a biomarker of oxidative stress. Also, a statistically significant negative correlation between homovanillyl alcohol (HValc, hydroxytyrosol's major metabolite, formed through the COMT system) and F(2)-isoprostanes excretion was found. Thus, the administration of oil samples with increasing, albeit low, concentrations of orthodiphenolic compounds, namely hydroxytyrosol and oleuropein aglycone, results in a dose-dependent reduction in the urinary excretion of 8-iso-PGF(2alpha). The statistically significant negative correlation between 8-iso-PGF(2alpha) and HValc urinary concentrations suggests that this metabolite better reflects the in vivo activities of hydroxytyrosol.

Adult↗
PubMed2000

Olive oil phenolics are dose-dependently absorbed in humans.

Olive oil phenolic constituents have been shown, in vitro, to be endowed with potent biological activities including, but not limited to, an antioxidant action. To date, there is no information on the absorption and disposition of such compounds in humans. We report that olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose-dependently absorbed in humans after ingestion and that they are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.

Adult↗
PubMed2000

Rapid evaluation of phenolic component profile and analysis of oleuropein aglycon in olive oil by atmospheric pressure chemical ionization-mass spectrometry (APCI-MS).

Epidemiological studies have linked the Mediterranean diet with a low incidence of cardiovascular diseases. Olive oil, the major fat component of this diet, is characterized by antioxidant properties related to their content in catecholic components, particularly oleuropein aglycon. Therefore quantification of these components in edible oils may be important in determining the quality, and consequently its commercial value. The present method allows us to obtain the profile of the phenolic components of the oil from the methanolic extracts of the crude olive oil. In particular tyrosol, hydroxytyrosol, elenolic acid, deacetoxyligstroside and deacetoxyoleuropein aglycons, ligstroside and oleuropein aglycons, and 10-hydroxy-oleuropein are clearly identified by atmospheric pressure chemical ionization-mass spectrometry (APCI-MS). Moreover, oleuropein and its isomers present in the oil are quantified by APCI-MS/MS analysis of the extracts without preliminary separation from other phenolic compounds.

Dietary Fats, Unsaturated↗
PubMed2000

Evidence of postprandial absorption of olive oil phenols in humans.

BACKGROUND AND AIM: Olive oil phenols are potent antioxidants in vitro. If this were to be also demonstrated in vivo, it would help to explain the beneficial effects of this typical ingredient of the Mediterranean diet. This study was designed to determine the presence in lipoprotein fractions of two phenolic compounds peculiar to extra virgin olive oil, namely tyrosol and OH-tyrosol, and whether their absorption induces an antioxidant effect in vivo. METHODS AND RESULTS: Two trials were performed. In the first (Long-term), 14 healthy volunteers followed two diets, each for one month. The only difference between the diets was that the first supplied 50 g of extra virgin olive oil per day, where-as the second one supplied 50 g of refined olive oil with no simple phenols, as demonstrated by GC-MS analysis. There were no changes in LDL oxidizability and tyrosol and OH-tyrosol were not recovered in lipoproteins and plasma from fasting samples drawn at the end of each diet period. In the second study (Postprandial), eight healthy volunteers received an oral fat load consisting of 100 g of extra virgin olive oil. Blood was drawn at times 0', 30', 60', 120', 240', 360', and major plasma lipoprotein classes were separated. The concentration of tyrosol, OH-tyrosol and vitamin E was determined in lipoprotein fractions. Plasma antioxidant capacity was measured by a crocin-bleaching test and expressed as mM Trolox C equivalents. Tyrosol and OH-tyrosol were recovered in all lipoprotein fractions, except VLDL, with concentrations peaking between 60' and 120'. However, a very high variability in tyrosol and OH-tyrosol absorption was observed among subjects. Vitamin E content of LDL and HDL did not vary significantly throughout the study. Plasma antioxidant capacity increased significantly at time 120' (baseline 0.96 mM Trolox; 120' 1.19 mM Trolox; p = 0.02), and then returned almost to baseline values after 360' (1.1 mM Trolox). CONCLUSIONS: These findings suggest that phenolic compounds in olive oil are absorbed from the intestine, though not through a pathway dependent on chylomicron formation, and may exert a significant antioxidant effect in vivo, probably in the postprandial phase.

Adolescent↗
PubMed1999

Oxysterols from oxidized LDL are cytotoxic but fail to induce hsp70 expression in endothelial cells.

Oxidized low density lipoprotein (OxLDL) possesses several proatherogenic characteristics, among which a marked cytotoxicity. In vitro, cytotoxicity of OxLDL to endothelial cells is associated with an increase in the expression of the inducible form of heat shock protein 70 (hsp70), generally regarded as a cytoprotective protein. Oxidized derivatives of cholesterol which form upon LDL oxidation are cytotoxic. Moreover, most of the OxLDL cytotoxicity is due to its lipid moiety, in particular to oxysterols. In this report we demonstrate that although oxysterols identified in OxLDL are cytotoxic, they cannot trigger the increase in hsp70 expression observed with intact oxidized lipoproteins. We speculate therefore that oxysterols may represent the most toxic form of oxidized lipids in LDL because they cannot activate a rescue mechanism (i.e. the hsp response) and may contribute significantly to cell death within atherosclerotic plaques.

Apoptosis↗
PubMed1999

Evaluation of growth hormone administration in patients with chronic heart failure secondary to coronary artery disease.

We have examined the effects of 6 months of treatment with growth hormone (GH) (0.02 U/kg/day) in 10 patients with chronic postischemic cardiac failure. Ten patients matched for age, body mass index, functional class, and ejection fraction served as a control group. In the GH group, 1 patient died and 2 were withdrawn from the study because of arrhythmia or worsening of heart failure. In the control group, 1 patient died and 1 patient was withdrawn from the study because of progressive heart failure. Among GH patients, those with an unfavorable outcome had a greater left ventricular end-diastolic diameter (79, 82, and 88 mm) on entry to the study than patients without adverse events (range 62 to 72 mm). At the end of the study, the seven GH patients reported a feeling of well-being and had a significant increase in their exercise test duration (462 +/- 121 vs 591 +/- 105 seconds, p <0.05). Low baseline insulin-like growth factor-I values were increased with GH treatment (189 +/- 52 vs 100 +/- 22 ng/ml, p <0.01). GH did not change left ventricular diameters or wall thickness. A trend toward decreased serum triglyceride levels and adipose body tissue associated with an increase in high-density lipoproteins was observed in the GH group. In conclusion, our present data support previous suggestions that GH treatment exerts some beneficial effects in patients with chronic, stabilized, moderately severe heart failure, but may have deleterious effects in patients with more severe heart failure.

Aged↗
PubMed1999

Effect of virgin olive oil phenolic compounds on in vitro oxidation of human low density lipoproteins.

BACKGROUND AND AIM: Substantial evidence suggests that oxidative modifications of low density lipoproteins (LDL) critically contribute to the pathogenesis and progression of human atherosclerosis. Oxidized LDL (oxLDL) are present in atherosclerotic plaques and contain oxysterols that exhibit a variety of adverse biological activities. Antioxidants have also been shown to prevent LDL modification. We have therefore assessed the efficacy of virgin olive oil phenolic compounds in preventing oxidative modifications of human LDL oxidized by UV light. METHODS AND RESULTS: Cholesterol oxides formed during LDL photo-oxidation were determined by UV-HPLC in the presence of different concentrations of phenolic compounds and their pure components (tyrosol and oleuropein), and probucol, a widely used synthetic antioxidant. Electrophoretic mobility was also assayed. The results demonstrate that phenolic compounds are much more potent in preventing cholesterol oxide formation and apoproteic moiety modification than their pure components and probucol. CONCLUSIONS: The beneficial effects of a Mediterranean diet may be ascribable not only to the high unsaturated/saturated fatty acid ratio characteristic of olive oil, but also to the unique antioxidant properties of its phenolic compounds.

Anticholesteremic Agents↗
PubMed1998

Diagnosis and treatment of bulimia nervosa.

Bulimia nervosa often has an obscure presentation that requires a high level of suspicion by physicians. Awareness of subtle signs and knowledge of important questions to pursue are critical to a physician's ability to diagnose this disorder. Since bulimia nervosa may have several comorbid psychiatric disorders, such as depression, substance abuse, and personality disorders, it is important to refer patients for further evaluation and treatment. The treatment of bulimia nervosa is comprehensive and individualized and may include cognitive-behavioral therapy, group therapy, family therapy, individual psychotherapy, pharmacotherapy, or hospitalization. The comorbid disorders must also be addressed with appropriate treatment such as a drug or alcohol rehabilitation program for substance abusers. Although the prognosis can be variable, the majority of bulimic patients have a serious chronic illness with remissions and exacerbations.

Adult↗
PubMed1996

Identification of 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide in human oxidized LDL.

Oxidized LDL exhibits cytotoxic activity towards endothelial cells, which is thought to be mediated by the products derived also from cholesterol oxidation, mainly involving the B-ring. By LC-PB-EI-MS and EI-MS/MS analysis, we have identified 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide among the cholesterol oxidation products in LDL incubated with micromolar concentrations of copper ions.

Cholesterol↗
PubMed1996

Insulin-like growth factor-I and angiographically documented coronary artery disease.

In conclusion, we have reported an association between low IGF-I concentrations and CAD in relatively young men. This observation raises the possibility that IGF-I deficiency could be part of the polymetabolic syndrome. Whether a subnormal IGF-I production is due to growth hormone secretory abnormalities or to other metabolic reasons (e.g., insulin resistance or fat distribution, or both) is still unknown.

Adult↗
PubMed1996

Cholesta-5,7,9(11)-trien-3 beta-ol found in plasma of patients with Smith-Lemli-Opitz syndrome indicates formation of sterol hydroperoxide.

The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by accumulation of cholesta-5,7-dien-3 beta-0l caused by a deficiency of the enzyme desaturating this sterol to cholesterol. In addition to other unusual sterols recently found in plasma of patients with SLOS, namely cholesta-5,8-dien-3 beta-ol and 19-nor-cholesta-5,7,9 (10)-trien-3 beta-ol we have detected a trienol and we describe here its identification as cholesta-5,7,9 (11)-trien-3 beta-ol by GC-MS and by comparison with a synthetic standard. We tested the possibility that the trienol may be formed by radical oxidation of cholesta-5,7-dien-3 beta-ol accumulated in plasma of patients with SLOS because it is known to be formed by decomposition of 7-hydroperoxy-cholesta-5,8-dien-3 beta-ol, which is a product of cholesta-5,7-dien-3 beta-ol photooxidation. Incubation of cholesta-5,7-dien-3 beta-ol with rat liver microsomes in the presence of ADP/Fe2+ and NADPH gave rise to a number of oxygenated sterols. Among these, analysis by particle-beam LC-MS under CI conditions indicated the presence of 7-hydroperoxy-cholesta-5,8-dien-3 beta-ol and of cholesta-5,7,9(11)-trien-3 beta-ol which is known to derive from the oxidation of the 7-hydroperoxide. From these results we conclude that cholesta-5,7-dien-3 beta-ol accumulated in tissues of patients with SLOS may be oxidized by oxygen radicals giving rise to oxygenated sterols. Some of these compounds may be toxic and may contribute to worsen the pathological picture in patients with SLOS.

Animals↗
PubMed1994

Formation of 22 and 24 carbon 6-desaturated fatty acids from exogenous deuterated arachidonic acid is activated in THP-1 cells at high substrate concentrations.

Deuterated arachidonic acid (AA, [2H8]20:4 n-6) 1-25 microM, is converted to other fatty acids, as evaluated by gas chromatography-mass spectrometry, in THP-1 cells. The major products, in the 1 to 10 microM range, are 22:4 (elongated) and 20:3 (reduced in 5). At 25 microM, 24:4, 24:5 and 22:5 accumulate, with [2H8]/[2H0] ratios higher than in AA. At high AA concentration preferential conversion to elongated fatty acids with 5 unsaturations, through a 6 desaturase takes place and the 4-desaturated 22:5 appears to be formed through beta-oxidation of 24:5.

Arachidonic Acid↗
PubMed1993

Quantitative changes of hydroxyacid formation during platelet-neutrophil interaction.

In recent years the interactions between lipoxygenase enzymes present in platelets and leukocytes, resulting in the transcellular biosynthesis of eicosanoids, have been discovered and their relevance in thrombotic and inflammatory disorders recognized. However, attention has focused on the synthesis of novel products, not normally formed by the single-cell population. Less information is available on the changes in hydroxyacid formation during platelet-neutrophil interactions. In this study, we evaluated the quantitative changes of the levels of 12- and 5-hydroxyeicosatetraenoic acids, leukotriene B4, and thromboxane B2 occurring during the incubation of platelet-neutrophil mixed suspensions stimulated with the calcium ionophore A23187. Cell-to-cell interaction resulted in quantitative changes of the level of hydroxyacids; in mixed platelet-neutrophil suspensions, the levels of 12-hydroxyeicosatetraenoic acid were significantly increased with respect to those measured in platelets incubated alone. The amount of 5-hydroxyeicosatetraenoic acid formed by neutrophils was significantly decreased by the presence of platelets in the incubation medium. In addition, a slight but significant reduction in leukotriene B4 synthesis was observed. Concomitantly with these changes, the formation of thromboxane B2 by platelets was modified, indicating that--besides the lipoxygenase pathway--the arachidonic acid metabolism by cyclooxygenase is affected. Our study demonstrates that in mixed platelet-neutrophil suspensions profound quantitative modifications in hydroxyacid and thromboxane synthesis occur, indicating that the overall balance of arachidonic acid products may be altered in pathologic conditions in which early events of multicellular origin have been recognized.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

A particle beam-liquid chromatography-mass spectrometry method for the determination of lipoxygenase metabolites of arachidonic acid.

An application of the particle beam-liquid chromatography-mass spectrometry technique to the quantification of hydroxyeicosatetraenoic acids (15-, 12-, and 5-HETE) in biological samples is presented. The acids are extracted with Ethyl acetate and then transformed into pentafluorobenzyl esters, thus increasing the sensitivity of their detection by negative chemical ionization mass spectrometry. Reverse-phase HPLC separation of HETEs is performed in about 10 min with a water-methanol gradient. The procedure shows a detection limit of nearly 0.5 pmol, about one order of magnitude lower than that of the widely used HPLC/UV methods. The quantitative determination is linear (r2 greater than 0.998) for all of the HETEs in the range tested (3-1500 pmol) and a CV lower than 8.5% was observed for repeated analysis of samples. As an application of the method, HETEs formed from endogenous arachidonate were evaluated in extracts obtained from coincubates of platelets and neutrophils stimulated with calcium ionophore A23187.

Adult↗