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Biomedical subjects

D Caruso

Publications and source records attributed to D Caruso.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1991

Arachidonic acid cycloxygenase and lipoxygenase pathways are differently activated by platelet activating factor and the calcium-ionophore A23187 in a primary culture of astroglial cells.

The aim of our study has been to investigate the metabolism of endogenous arachidonic acid or that of radiolabeled arachidonate in astroglial cells, stimulated with platelet activating factor (PAF) and with the calcium-ionphore A23187. Primary cultures of astroglial cells were obtained from brain cortex of one-day-old rats and were characterized by immunofluorescent staining vs glial fibrillary acidic protein. In labeled cells, diacylglycerol was formed after stimulation with platelet activating factor, whereas mainly the release of labeled arachidonic acid from phospholipids was observed after stimulation with calcium-ionophore. Both PAF and the calcium-ionophore A23187 actively stimulated the formation of the cycloxygenase products PGD2, TXB2 and 6-keto-PGF1 alpha, measured by radio- or enzyme-immunoassay. Differences were observed, instead, in the formation of the lipoxygenase metabolites, the hydroxyeicosateraenoic acids, which were measured by high pressure liquid chromatography (HPLC) with on line radiodetection for the labeled products, and Leukotriene C4, measured by radioimmunoassay. The formation of hydroxyacids by stimulated cells was confirmed by gas chromatography-mass spectrometry (GC-MS). In labeled cells, both agonists induced the formation of 12- and 15-hydroxyeicosatetraenoic acids, whereas stimulation of unlabeled cells with calcium ionophore resulted in formation of 12-hydroxyeicosatetraenoic acid and Leukotriene C4. Our results suggest that in astroglial cells, PAF, a compound which is produced in several tissues including brain, mobilizes a selected arachidonic acid pool, possibly associated with diacylglycerol production, from phospholipids, thus activating the conversion of the released fatty acid via the cyclo and the 12-lipoxygenase pathways.

Animals↗
PubMed1989

Albumin interferes with arachidonate metabolism in platelets and neutrophils.

The in vitro effects of albumin (150-600 microM) on arachidonate metabolism are compared in two types of circulating cells, platelets and neutrophils. The effect of this plasma protein on a functional aspect common to both these blood components, i.e. aggregation, was also investigated. Bovine serum albumin (BSA) significantly inhibited thromboxane B2 formation by washed platelets stimulated with threshold concentrations of collagen. In addition, this protein profoundly affected the formation of the major products via the lipoxygenase pathways, i.e., 12-hydroxyeicosatetraenoic acid and leukotriene B4 by platelets and neutrophils, respectively. This inhibitory effect was also confirmed for both types of cells considered on aggregation. Albumins of human origin and human plasma behaved similarly to BSA on the above parameters. Although the mechanism(s) responsible for the described effects require(s) additional studies, albumin, affecting platelet and neutrophil arachidonate metabolism, as well as the aggregatory response, might influence, in some conditions, cell activation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Differential effects of oral administrations to human volunteers of acetylsalicylic acid, sodium salicylate and indomethacin on 12-hydroxyeicosatetraenoic acid formation by stimulated platelets.

The effects of single oral administrations of acetylsalicylic acid (ASA, 500 mg), indomethacin (Indo, 50 mg) and sodium salicylate (NaSal, 400 mg) on platelet aggregation and on the thromboxane B2 (TXB2) and 12-hydroxyeicosatetraenoic acid (12-HETE) synthesis by platelet rich plasma (PRP) stimulated with collagen were evaluated. While both ASA and Indo significantly inhibited TXB2 synthesis and platelet aggregation, significant reduction of 12-HETE formation at 2 and 6 h after the administration of the drug, was detected only in subjects who ingested ASA. NaSal did not affect any of the tested parameters. The comparison of the effect of ASA (200 mg) on 12-HETE synthesis in washed platelets and PRP shows that the drug is able to affect this parameter only in PRP. To obtain a constant inhibition of 12-HETE synthesis in PRP over a 24 h period, a repeated ASA treatment schedule was assessed (ASA 200 mg every 6 h for 5 times). TXB2 synthesis in PRP was almost completely suppressed at 2 h after the first ASA administration and inhibition remained constant up to 48 h after the last ASA intake. As far as 12-HETE synthesis by stimulated PRP is concerned, a significant reduction of this parameter was detected at 4 h after the first drug administration and the levels remained almost constant following the repeated administrations during a 24 h period. These data indicate that ASA, but not Indo and NaSal, significantly affect not only TXB2 synthesis but also 12-HETE formation in PRP. The lack of the effect of ASA administration on 12-HETE, found when studies were carried out in washed platelets, indicates that the drug requires the presence of plasma factors for its activity on the formation of 12-lipoxygenase products by platelets.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Arachidonic acid metabolism in HEL/30 murine epidermal cell line.

The established mouse epidermis-derived cell line HEL/30 was incubated in the presence of 3H arachidonic acid (AA) for 1 h. After medium removal, cells were reincubated with fresh medium in the presence or absence of the calcium ionophore A23187 and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The AA metabolites formed were extracted from cell-free medium and analyzed using TLC and HPLC. The distribution of the recovered radioactivity showed PGE2, 15-hydroxy-eicosatetraenoic acid (15-HETE), and leukotriene B4 (LTB4), as major products of AA metabolism. The presence of calcium ionophore A23187 increased the release of radioactivity, without affecting the profile of metabolites present in the medium. TPA elicited a preferential increase of cycloxygenase metabolism, this effect being reversed by indomethacin. 5,8,11,14-eicosatetraynoic acid (ETYA) almost completely inhibited LT and HETE formation in A23187 and TPA-treated cells. The results show that HEL/30 cells are able to metabolize AA via both cyclo- and lipoxygenase pathways and that these activities can be modified by chemical means. This cell line might be a suitable tool for studying the involvement of arachidonic acid cascade in cell response to exogenous stimuli.

Animals↗
PubMed1988

Effect of single oral administrations of non steroidal antiinflammatory drugs to healthy volunteers on arachidonic acid metabolism in peripheral polymorphonuclear and mononuclear leukocytes.

The effects of a single oral administration of acetylsalicylic acid (500 mg), indomethacin (50 mg) and piroxicam (40 mg) to healthy volunteers on functional and biochemical parameters of platelets, polymorphonuclear (PMN) and mononuclear (MNL) leukocytes were evaluated. Blood was collected before and two hours after the drug intake and blood cells separated according to conventional techniques. The considered drugs almost completely suppressed the aggregation of platelets, whereas they did not affect either PMN and MNL aggregation. Superoxide anion generation by leukocytes was (PMN), or no effect (MNL) was observed after piroxicam and indomethacin respectively. The formation of arachidonate metabolites via the 5-lipoxygenase pathway by PMN and MNL challenged with 10 microM A23187 was unchanged following aspirin and indomethacin. In this respect a selective increase of 5-HETE and LTC4 synthesis by MNL only was detected after piroxicam administration. The three drugs similarly reduced TXB2 synthesis by platelets and PMN (-80% for aspirin and indomethacin, and -40% for piroxicam). As far as MNL is concerned, aspirin inhibited this metabolite by 80%, while indomethacin reduced it by 40% only. In contrast piroxicam increased TXB2 synthesis by stimulated MNL. It can be concluded that the considered antiinflammatory drugs 1) differently affect the cyclooxygenase enzyme in platelets and leukocytes; 2) at variance with the situation in platelets, the inhibition of thromboxane formation by leukocytes is not related to modifications of cellular function; 3) the formation of arachidonate metabolites via the 5-lipoxygenase pathway is affected by piroxicam only.

Adult↗
PubMed1988

Nonsteroidal antiinflammatory drugs aggravate acute myocardial ischemia in the perfused rabbit heart: a role for prostacyclin.

Myocardial ischemia was induced in perfused paced isovolumic left heart preparation of the rabbit by reducing, for a period of 40 min, the flow rate from 20 ml/min to 0.2 ml/min (severe model) and to 1 ml/min (moderate model). The relationship between prostaglandin biosynthesis and cardiac ischemic damage was evaluated in the two experimental models. The results obtained indicate that the total amount of 6-keto-PGF1 alpha generated increases with the severity of the ischemia, particularly during the 20 min of reperfusion (moderate model 81.8 +/- 13.7 ng: severe model 375 +/- 102 ng). The inhibition of the prostaglandin synthesis, prostaglandin-E2, and 6-keto-prostaglandin-F1 alpha (PGE2 and 6-keto-PGF1 alpha levels below the detection limits) by Aspirin (20 micrograms/ml) and Indomethacin (1 microgram/ml) in moderate myocardial ischemia was correlated with greater increments in resting diastolic tension (nearly 100% and 40%, respectively). This phenomenon was also associated to a further decrease on cardiac contractility and increase on coronary perfusion pressure upon reperfusion. On the contrary drugs which stimulated prostaglandin generation in myocardial tissue, such as Defibrotide (400 micrograms/ml), completely protected the organ from ischemia. U-60257 (3 micrograms/ml) and FPL-55712 (2 micrograms/ml), compounds, which respectively inhibits biosynthesis and the effects of leukotrienes, displayed a beneficial activity on this moderate model of ischemia. The present data suggests that the deleterious effect of nonsteroidal antiinflammatory drugs in low flow myocardial ischemia and reperfusion damage may be associated with removal of PGI2 and PGE2 from ischemic myocardium.

Animals↗
PubMed1988

Proinflammatory lipoxygenase products from peripheral mononuclear cells in patients with rheumatoid arthritis.

The formation of 5-lipoxygenase products (5-hydroxyeicosatetraenoic acid [5-HETE], leukotriene B4 [LTB4], and leukotriene C4 [LTC4]) by polymorphonuclear and mononuclear leukocytes isolated from peripheral blood of patients with rheumatoid arthritis was evaluated and compared with the data obtained from a group of control subjects. Although the levels of arachidonic acid metabolites via 5-lipoxygenase pathway by stimulated polymorphonuclear cells were comparable between patients and controls, mononuclear leukocytes from patients synthesized, when stimulated, significantly greater amounts of 5-HETE, LTB4, and LTC4 than did cells isolated from normal subjects. In addition, the release of superoxide anion, stimulated by either a particulate or a soluble stimulus, was increased in mononuclear cells from patients. The enhanced capacity of peripheral mononuclear leukocytes isolated from patients with rheumatoid arthritis to generate proinflammatory metabolites of arachidonic acid and oxygenated species with bactericidal and tissue-damaging properties may contribute to the pathogenesis of this complex disease.

Arthritis, Rheumatoid↗
PubMed1988

Leukotriene B4 production in human atherosclerotic plaques.

We evaluated the hypothesis that leukotriene (LT) B4, a potent chemotactic and endothelium-permeabilizing autacoid, may be a factor in the progression of the atherosclerotic lesion. Human vascular fragments, freshly obtained at vascular surgery from saphenous veins, atrial appendages, normal aortas and atherosclerotic lesions (histologically classified as fibrous plaques, fatty plaques and complicated lesions) were incubated at 37 degree C with mechanical agitation, for various times ranging between 5 and 60 minutes, sequentially, with buffer (basal), ionophore A23187 (IONO), and arachidonic acid (AA). After each step medium was assayed for LTB4 production by radioimmunoassay. Incubations were also performed in a chamber allowing selective exposure of the endothelial surface to the medium. Basal production (15 minute incubation, ng/g, mean +/- SD) was lowest for fibrous plaques (0.9 +/- 0.2, n = 38) and saphenous veins (1.0 +/- 0.3, n = 32) and much higher (P less than 0.01) for fatty plaques (7.3 +/- 2.2, n = 35) and complicated lesions (5.3 +/- 3.0, n = 28). A virtual abolition of production was observed after boiling of the vascular fragment. Production was increased in the presence of AA and IONO (in atheromas: 11.5 +/- 4.2 AND 14.3 +/- 5.3, respectively, with 15 minutes incubation), and decreased after incubation with 5-lipooxigenase inhibitors. Peak of ionophore or arachidonic acid-stimulated production in kinetic studies was reached at 20 minutes. LTB4 production was able to reach the luminal surface in both basal and stimulated conditions. There was no relationship with concomitantly measured prostacyclin production (mainly endothelial), while a correlation was found between LTB4 levels and degree of white cell infiltration in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid↗
PubMed1988

Single dose pharmacokinetics of aminoglutethimide by a rapid SIM methodology.

The kinetics of unchanged aminoglutethimide and of its major metabolite N-acetylaminoglutethimide were investigated in healthy volunteers with a new multiple selected ion monitoring (SIM) technique. This method allows a rapid detection of both the unchanged drug and of its metabolite with a single injection and after minimal handling of the samples. This rapid method provided similar kinetic findings, compared to those described with the more time consuming high pressure liquid chromatographic (HPLC) procedure. Moreover, the SIM method allowed the detection of the N-acetylamino metabolite in plasma at longer time intervals vs. the HPLC method. Some typical features of the kinetic behavior (e.g., a discontinuity in the plasma die-away curve for both unchanged drug and metabolite), attributable to partial liver extraction, could also be more clearly observed with the new procedure. This new, rapid technique confirms that aminoglutethimide and N-acetylaminoglutethimide have very similar plasma die-away curves in subjects with a normal conjugating capacity, and that kinetic patterns or individual blood levels can be readily obtained by SIM with minimal acquisition of supplementary equipment.

Adult↗