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Biomedical subjects

G Davi

Publications and source records attributed to G Davi.

At least 19 recordsLinked to original sources
PubMed2001

5-lipoxygenase regulates malignant mesothelial cell survival: involvement of vascular endothelial growth factor.

Evidence indicates that lipoxygenases (LO) may play a role in cancer cell survival. We show that human malignant pleural mesothelial (MM) cells, but not normal mesothelial (NM) cells, express a catalytically active 5-LO. Pharmacological or genetic inhibition of MM cell 5-LO determined nucleosome formation and induced a DNA fragmentation pattern typical of apoptosis. This was completely reversed by exogenously added 5(S)-HETE but not by 12(S)-, 15(S)-HETE, or leukotriene (LT)B4. A 5-LO antisense oligonucleotide potently and time-dependently reduced vascular endothelial growth factor (VEGF) mRNA and constitutive VEGF accumulation in the conditioned media of MM cells. When NM cells were transfected with a 5-LO cDNA, basal and arachidonic acid-induced VEGF formation increased consistently by 6- and 12-fold, respectively. This was associated with a significant increase in DNA synthesis that was counteracted by a specific anti-VEGF antibody. Arachidonic acid and 5(S)-HETE also potently stimulated the activity of a VEGF promoter construct. Thus, 5-LO is a key regulator of MM cell proliferation and survival via a VEGF-related circuit.

Apoptosis↗
PubMed2000

Homocysteine, coagulation, platelet function, and thrombosis.

Over the last 30 years, a growing body of evidence has documented the role of hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the mechanisms through which elevated circulating levels of homocysteine (Hcy) cause vascular injury and promote thrombosis remain elusive. Most findings have been achieved in in vitro studies employing exceedingly high concentrations of Hcy, whereas only a few studies have been carried out in vivo in humans. In homocystinuric patients, homozygotes for mutations of the gene coding for the cystathionine beta-synthase enzyme, abnormalities of coagulation variables reflecting a hypercoagulable state, have been reported. In vitro studies provide a biochemical background for such a state. In homocystinuric patients, an in vivo platelet activation has also been reported. The latter abnormality is not corrected by the bolus infusion of concentrations of hirudin, which determines a long-lasting impairment of the conversion of fibrinogen to fibrin by thrombin; in contrast, it appears at least in part lowered by the administration of the antioxidant drug probucol. During the autooxidation of Hcy in plasma, reactive oxygen species are generated. The latter initiate lipid peroxidation in cell membranes (potentially responsible for endothelial dysfunction) and in circulating lipoproteins. Oxidized low-density lipoproteins (LDL) may trigger platelet activation as well as some of the hemostatic abnormalities reported in such patients. Thus the oxidative stress induced by Hcy may be a key process in the pathogenesis of thrombosis in HHcy. Accumulation of adenosylhomocysteine in cells (a consequence of high circulating levels of homocysteine) inhibits methyltransferase enzymes, in turn preventing repair of aged or damaged cells. This mechanism has been recently documented in patients with renal failure and HHcy and provides an additional direction to be followed to understand the tendency to thrombosis in moderate HHcy.

Adolescent↗
PubMed1997

In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia.

F2-isoprostanes are bioactive prostaglandin (PG)-like compounds that are produced from arachidonic acid through a nonenzymatic process of lipid peroxidation catalyzed by oxygen free-radicals. 8-Epi-PGF2 alpha may amplify the platelet response to agonists, circulates in plasma, and is excreted in urine. We examined the hypothesis that the formation of 8-epi-PGF2 alpha is altered in patients with hypercholesterolemia and contributes to platelet activation in this setting. Urine samples were obtained from 40 hypercholesterolemic patients and 40 age- and sex-matched control subjects for measurement of immunoreactive 8-epi-PGF2 alpha. Urinary excretion of 11-dehydro-thromboxane (TX) B2, a major metabolite of TXA2, was measured as an in vivo index of platelet activation. Low-dose aspirin, indobufen, and vitamin E were used to investigate the mechanism of formation and effects of 8-epi-PGF2 alpha on platelet activation. Urinary 8-epi-PGF2 alpha was significantly (P = .0001) higher in hypercholesterolemic patients than in control subjects: 473 +/- 305 versus 205 +/- 95 pg/mg creatinine. Its rate of excretion was inversely related to the vitamin E content of LDL and showed a positive correlation with urinary 11-dehydro-TXB2. Urinary 8-epi-PGF2 alpha was unchanged after 2-week dosing with aspirin and indobufen despite complete suppression of TX metabolite excretion. Vitamin E supplementation was associated with dose-dependent reductions in both urinary 8-epi-PGF2 alpha and 11-dehydro-TXB2 by 34% to 36% and 47% to 58% at 100 and 600 mg daily, respectively. We conclude that the in vivo formation of the F2-isoprostane 8-epi-PGF2 alpha is enhanced in the vast majority of patients with hypercholesterolemia. This provides an aspirin-insensitive mechanism possibly linking lipid peroxidation to amplification of platelet activation in the setting of hypercholesterolemia. Dose-dependent suppression of enhanced 8-epi-PGF2 alpha formation by vitamin E supplementation may contribute to the beneficial effects of antioxidant treatment.

Antioxidants↗
PubMed1995

Prolonged inhibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy volunteers.

This study addressed two questions: 1) whether a relatively low dose of n-3 fatty acid ethyl esters (n-3 FAs) administered to healthy volunteers for a prolonged period of time would exert beneficial effects on plasma lipids, platelet function, and thromboxane biosynthesis; and 2) whether a short-term loading treatment (6 wk) with 6 g n-3 FAs/d followed by 12 wk with 3 g/d results in more pronounced effects. After 6 wk treatment a reduction of plasma triglyceride concentration and an accumulation of EPA and DHA in plasma were observed. A longer period of treatment with n-3 FAs was necessary to affect platelet aggregation and thromboxane A2 biosynthesis. At 12 and 18 wk, platelet aggregation, thromboxane A2 formation, and the excretion of thromboxane metabolites in urine were reduced, particularly in subjects who received 6 g n-3 FAs/d during the initial 6 wk. After treatment ended, triglyceride and thromboxane A2 biosynthesis returned to baseline values within 4 wk, whereas platelet aggregation remained impaired for > or = 14 wk. The longlasting impairment in platelet aggregation was accompanied by the retention of n-3 FAs in platelet phospholipids.

Administration, Oral↗
PubMed1994

Anti platelet property of anti-single-stranded DNA antibodies in type 1 (insulin-dependent) diabetes mellitus.

Nineteen of 50 sera from children with type 1 (insulin-dependent) diabetes mellitus showed anti-platelet reactivity. This reactivity was significantly associated with the presence of proteoglycan cross-reactive anti-ssDNA antibodies. As well as DNA-anti-DNA interaction, increasing salt concentration of the dilution buffer caused a decrease in the binding of positive sera to platelets. Purified ssDNA inhibited also the anti-platelet reactivity of anti-ssDNA positive sera. The addition of purified IgG from anti-ssDNA positive but not from anti-ssDNA negative sera to washed platelets caused an increased collagen-induced platelet aggregation similar to that obtained with the addition of polycationic agents. It may be suggested that ionic interaction between anti-negative charged molecule antibodies (such as anti-ssDNA antibodies) and platelet surface negative charges may be a pathophysiological mechanism contributing to the altered platelet function observed in diabetes.

Adolescent↗
PubMed1990

[Bilateral choroidal osteoma in an aged patient].

The authors report a case of choroidal osteoma in an elderly patient. The affection was bilateral and multifocal. This rare benign tumor mostly affects young females. We report the outcome of the clinical and instrumental examinations leading to the diagnosis of choroidal osteoma. The patient underwent retinal fluoroangiography, A and B-scan ocular ultrasonography, Computerized Axial Tomography (CAT) with and without dye, orbit RNM, and electroretinography. The same investigations were performed 6-7 months after the first control. No changes in the findings were found except for retinal fluoroangiograms that revealed an increased area of the most central lesion in the right eye. Particularly relevant among these diagnostic techniques were ocular ultrasonography and CAT, which revealed the osseous nature of the tumor. Contact B-scan ultrasound examination showed a small number of dense opacities in both eyes. In the retrobulbar area the tumor caused diminution in echo amplitude. A-scan examination showed high reflectivity peaks (100%) corresponding to the lesion that were detectable even with reduced sensitivity of the system and, in the orbit, low reflectivity that confirmed the tumor's enhanced ultrasound absorption. CAT detected small calcified areas corresponding to the location of the lesions. Haematochemical examinations performed at each control to measure blood calcium, phosphate and alcaline phosphatase were in the normal range. Urinalysis also excluded possible systemic affections underlying the chorioretinal pathology. We discuss possible pathogenetical hypothesis focusing on the age and sex of the patient. These factors in fact, rule out both the hypothesis of a osteogenesis inhibiting factor present in the last 20-30 years of age and the hypothesis of endocrine stimulation in female patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Thromboxane biosynthesis in cardiovascular diseases.

Sudden fissuring of an atherosclerotic plaque has been suggested as the primary trigger of transient spontaneous ischemia in both the coronary and cerebral circulation. Measurements of urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2, as well as results of Aspirin trials, have suggested that episodic platelet activation at the site of this acute vascular lesion is mediated, at least partly, by enhanced thromboxane (TX) A2 biosynthesis. Thus, episodic increases in metabolite excretion have been detected in unstable angina. Aspirin (75-325 mg/day) prevents about one third of all fatal and nonfatal thrombotic events in this setting. That a similar "dynamic" thrombotic process occurs during the early phase of acute myocardial infarction is suggested by thromboxane metabolite measurements and by the results of the ISIS-2 trial showing a similar impact of short-term Aspirin therapy to that seen in unstable angina. Percutaneous transluminal coronary angioplasty is associated with transiently enhanced TXA2 biosynthesis and Aspirin-suppressable periprocedural thrombotic complications. On the other hand, both non-insulin-dependent diabetes mellitus and type IIa hypercholesterolemia are associated with a relatively reproducible and persisting abnormality of TXA2-dependent platelet function. This association is likely to reflect a systemic rather than localized stimulus to platelet activation and a continuous rather than episodic alteration. Low-dose (50 mg/day) Aspirin can largely suppress thromboxane metabolite excretion in both diseases. Thus, low-dose Aspirin and/or selective prostaglandin H2/TXA2-receptor antagonists may be important tools to test the hypothesis that TXA2-dependent platelet activation represents an important transducer of the enhanced thrombotic risk associated with these metabolic abnormalities.

Aspirin↗
PubMed1989

Fractional conversion of thromboxane B2 to urinary 11-dehydrothromboxane B2 in man.

Thromboxane (TX) B2, the chemically stable hydration product of pro-aggregatory TXA2, undergoes two major pathways of metabolism in man, resulting in the formation of 2.3-dinor-TXB2 and 11-dehydro-TXB2, respectively. We have measured the excretion of the latter during the infusion of exogenous TXB2 over a 50-fold dose range in order to examine the fractional conversion of TXB2 to urinary 11-dehydro-TXB2 and to re-assess the rate of entry of endogenous TXB2 into the circulation. Four healthy male volunteers received 6-h intravenous infusions of the vehicle alone and TXB2 at 0.1, 1.0 and 5.0 ng.kg-1.min-1 in random order. They were pretreated with aspirin 325 mg/d in order to suppress endogenous TXB2 production. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured before, during and up to 24 h after the infusions and in aspirin-free periods, by means of NICI-GC/MS-validated radioimmunoassays. Aspirin treatment suppressed urinary 11-dehydro-TXB2 by 91%. The fractional elimination of 11-dehydro-TXB2 was independent of the rate of TXB2 infusion and averaged 6.8 +/- 0.7%, as compared to 6.4 +/- 0.9% for 2,3-dinor-TXB2. Interpolation of 11-dehydro-TXB2 values obtained in aspirin-free periods onto the linear relationship between the quantities of infused TXB2 and the amount of metabolite excreted in excess of control values (y = 0.0058x, r = 0.94, P less than 0.001) permitted calculation of the mean rate of entry of endogenous TXB2 into the circulation as 0.12 ng.kg-1.min-1. We conclude that: (a) urinary 11-dehydro-TXB2 is at least as abundant a conversion product of exogenously infused TXB2 as 2,3-dinor-TXB2; (b) its excretion increases linearly as a function of the rate of entry of TXB2 into the circulation up to approx. 40-fold the calculated rate of secretion of endogenous TXB2; (c) the latter is consistent with previous estimates based on monitoring of the beta-oxidation pathway of TXB2 metabolism.

Adult↗
PubMed1988

Bullous retinal detachment in diffuse retinal pigment epitheliopathy.

Central serous choroidopathy can occur in an atypical, severe clinical expression also known as diffuse retinal pigment epitheliopathy. We report two cases in which this affection was complicated by a bullous retinal detachment of the lower quadrants. In one case the subretinal leaking point was photocoagulated. The evolution was favourable in both cases with resolution of the detachment and partial recovery of the visual acuity.

Adult↗
PubMed1987

Laser treatment of macular subretinal neovascularizations in angioid streaks.

A serous hemorrhagic maculopathy with a subretinal neovascular membrane appears in about 70% of cases of angioid streaks. In this study a series of 60 eyes (31 patients) was reviewed. In 13 eyes macular subretinal neovascularizations were photocoagulated with blue-green argon laser, green argon laser, dye laser (rhodamine 6G) at 590 nm and red krypton laser. The authors present and discuss the results obtained and suggest that photocoagulation of subretinal new vessels not involving the fovea can be worth performing.

Adolescent↗
PubMed1986

[Dacryoscintigraphy: execution and examination technic in normal subjects].

After instillation of 0.013 ml of 99 mTc (equal to 60 microcuries), the authors performed a dacryoscintigraphy of the lacrymal ducts in 32 patients. The patients, between 6 and 80 year old, were divided in 4 age groups. None of them suffered from any diseases in the lacrymal apparatus or rhinopharynx. By this technique the authors studied the physiologic flow of tears, which varied with age and morphology of the ducts. They come to the conclusion that this non-invasive semeiological technique is much helpful in quantitative or qualitative study of the lacrymal ducts.

Adolescent↗
PubMed1986

Thymic hormone dependent immunodeficiency in an infant with partial trisomy of chromosome 22.

An infant with partial trisomy 22 syndrome and recurrent infections showed severe cellular immunodeficiency and serum IgG reduction. A marked increase of E-RFCs was observed after in vitro incubation of peripheral blood lymphocytes with thymostimulin (TS), a calf thymic extract. The treatment with TS resulted in reduction of infections, correction of cellular immunodeficiency and increase of IgG levels. Such a primary thymic hormone dependent immunodeficiency may be due to an altered development of branchial arches, commonly present in trisomy 22 syndrome. The same pathogenetic mechanism may account for thymus dysplasia observed in other chromosomal syndromes.

Cells, Cultured↗
PubMed1984

Double-blind, crossover study of the clinical efficacy and the hemorheological effects of pentoxifylline in patients with occlusive arterial disease of the lower limbs.

The effect of a 3 month daily administration of 800 mg pentoxifylline (Trental 400 bds) or placebo was assessed under double blind crossover design in 18 patients (12 males and 6 females) with peripheral occlusive arterial disease in respect of painfree walking distance and various hemorheological and hemostasiological variables, platelet aggregation, serum cholesterol and triglycerides. In first treatment period walking distance significantly increased with pentoxifylline by 46% from baseline 121 +/- 15 m and by 4% with placebo from baseline 134 +/- 18 m. Pentoxifylline administration furthermore yielded significant decrease in whole blood and plasma viscosity and significant increase in erythrocyte deformability. This was paralleled by distinct reduction of fibrinogen, platelet aggregation and euglobulin lysis time, also plethysmographic variables showed positive changes pointing to improvement of limb perfusion. The results of the study suggest that treatment of peripheral occlusive vascular disease by a drug improving blood fluidity through correction of hemorheological and hemostasiological factors turns especially promising and beneficial since the action centers finally on the languishing microcirculation in the ischemic tissue.

Adenosine Diphosphate↗