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Biomedical subjects

B Giusti

Publications and source records attributed to B Giusti.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients.

Several studies have shown that n-3 polyunsaturated fatty acids (n-3 PUFA) are able to lower blood pressure (BP) in humans, but large doses of fish oils have been often used. Moreover, most of the studies available in the literature were not able to evaluate the specific effects of n-3 PUFA because they employed fish oils which contain, together with n-3 PUFA, many other different components. The aim of this preliminary study was to evaluate if medium-term supplementation with a moderate dose of highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters is able to reduce BP in mild hypertensive patients. Sixteen mild essential hypertensive (diastolic BP: 95-104 mm Hg), non-diabetic, normolipidemic male outpatients and 16 normotensive male controls were recruited to participate in the study. Both hypertensive and control subjects were randomly assigned to receive either EPA and DHA ethyl esters (2.04 g EPA and 1.4 g DHA) as active treatment or olive oil (4 g/day) as a placebo for a period of 4 months. These subjects were followed up with 24-hour ambulatory BP monitoring and blood chemistry analyses at 2 and 4 months of treatment and 2 months after its discontinuation. The intake of n-3 PUFA was checked by red blood cell (RBC) phosphatidylcholine (PC) fatty acid composition. The effect of n-3 PUFA on BP in the active group was maximum after 2 months. Both systolic (-6 mm Hg, p<0.05) and diastolic (-5 mm Hg, p<0.05) BP significantly decreased during the n-3 PUFA ethyl ester supplementation. No further effect was observed at 4 months with a return to baseline values during the recovery period. These data indicate that 4 g/day of highly purified EPA + DHA ethyl esters are able to favorably affect BP in mild hypertensives.

Adult↗
PubMed1998

Evaluation of clotting and fibrinolytic activation after protracted physical exercise.

The behavior of hemostatic system activation during protracted physical exercise is well known, but the duration of its modification is not yet defined. In order to evaluate the time of hemostatic system activation after prolonged strenuous endurance physical exercise (typical marathon race: 42.195 km, v=15.35 km/h; mean length of time run 2.45+/-0.15 hours) 12 well-trained long-distance male runners (mean age: 35+/-7, range 25-47 years) were investigated. Blood samples were drawn in the morning on the day before the performance, immediately after the race, and 24 hours and 48 hours after the end of run. With respect of baseline, immediately after the race, a significant decrease of fibrinogen (-25%) and significant increases of prothrombin fragment 1+2 (+633%) and thrombin-antithrombin complex (+848%) were observed. A significant acceleration of euglobulin lysis time (-41%), and rises of plasma levels of tissue plasminogen activator antigen (+361%), plasminogen activator inhibitor type 1 antigen (+235%), d-dimer (+215%), and plasma fibrinogen degradation products (+1200%) were also found. Only a slight, yet not significant, decrease in plasminogen activator inhibitor type 1 activity was observed. One day after the end of marathon different parameters were still unchanged. Forty-eight hours after the competition all parameters investigated returned to baseline values. These results indicate a persistence of clotting as well as fibrinolysis activation up to 24 hours after the end of the race.

Adult↗
PubMed1998

Effect of low-dose heparin on fibrinogen levels in patients with chronic ischemic heart disease.

Several prospective studies have demonstrated that high plasma fibrinogen levels are associated with an increased risk of ischemic heart disease. Since in most patients an increased thrombin generation has been reported, we investigated whether the control of thrombin generation could affect plasma fibrinogen levels. Forty male outpatients (20 asymptomatic with previous myocardial infarction and 20 with stable effort angina) were enrolled in a randomized medium-term (6 months) cross-over study. Clottable fibrinogen, according to Clauss, prothrombin fragment 1 + 2, thrombin-antithrombin complex, and fibrinopeptide A were evaluated in relation to treatment with low-dose heparin. After a 15-day wash-out period, during which patients had been treated only with nitrates if needed, patients were allocated to two sequential periods of treatment with standard heparin (12,500 U, subcutaneously daily) plus antianginal treatment or antianginal treatment alone, separated by a second 15-day wash-out period. At the end of the treatment period with low-dose heparin significant decreases in the plasma fibrinogen (2.5 +/- 0.6 g/l vs. 3.3 +/- 0.5 g/l, P < 0.001), prothrombin fragment 1 + 2 (1.4 +/- 0.5 nmol/l vs. 1.9 +/- 0.7 nmol/l, P < 0.001), thrombinantithrombin (4.5 +/- 2.4 ng/ml vs. 9.7 +/- 3.6 ng/ml, P < 0.001), and fibrinopeptide A (2.1 +/- 1.1 ng/ml vs. 3.5 +/- 2.1 ng/ml, P < 0.001) were observed compared with the period without heparin. The present results indicate that low-dose heparin can effectively control the increased abnormal thrombin generation and elevated fibrinogen levels in patients with ischemic heart disease, possibly decreasing the risk of cardiovascular death.

Aged↗
PubMed1998

Cytokine gene expression in human LPS- and IFNgamma-stimulated mononuclear cells is inhibited by heparin.

In addition to its well-understood anticoagulant activity, heparin is known to modulate a variety of biological functions including immunologic responses. In order to investigate whether heparin influences the humoral immunity by interacting with cellular elements and affecting gene expression in blood circulating cells. we studied the effect of heparin on IL-1beta, IL-6 and TNFalpha mRNAs in human lipopolysaccharide-(LPS)- or interferon-gamma(IFN-gamma)-stimulated mononuclear cells. The study of mRNA was carried out by an initial PCR screening followed by a Northern blot quantitative analysis. Heparin (0.5 U/ml) turned out to inhibit all three cytokine gene expressions. The mRNA decrease was 37 +/- 6% for IL-1beta, 53 +/- 3% for IL-6 and 47 +/- 4% for TNFalpha with LPS stimulus. No differences could be observed in the inhibitory effect of heparin on IFNgamma-stimulated cells. This effect of heparin was confirmed in a subset of experiments performed on purified monocytes. These results suggest an important immunosuppressive effect of heparin on cell-mediated immune responses.

Anticoagulants↗
PubMed1997

Effects of estrogen replacement therapy on thrombin generation.

The aim of this study was to investigate the hemostatic system in menopausal women before and after three months of treatment with transdermal estradiol (TTS 50, 50 micrograms/die, n = 13) or coniugated equine estrogen (CEE, 0.625 mg/die, n = 9) by evaluating : beta-thromboglobulin, platelet factor 4, factor VIIag, factor VIIc, fibrinopeptide A-FPA-, thrombin-antithrombin-TAT-complexes, antithrombin-AT-activity, protein C, plasma fibrinolytic activity (euglobulin clot lysis time), plasminogen and antiplasmin activity. FPA levels significantly increased during TTS 50 treatment (p < 0.001) while protein C showed a slight but significant decrease in both treatments (TTS 50 p < 0.001, CEE p < 0.05). TAT complexes and AT were found unaltered. Platelet function and fibrinolytic activity did not significantly change. A significant relationship between FPA and estradiol levels, which were significantly increased during. TTS 50 therapy, was found (r = 0.40, p < 0.05). These findings indicate that unopposed estradiol given by transdermal route induces a slight but significant blood clotting activation, which seems strictly related to its biological activity.

Administration, Cutaneous↗
PubMed1997

A major involvement of the cardiovascular system in patients affected by Marfan syndrome: novel mutations in fibrillin 1 gene.

The aim of our study was to characterize the molecular defect in Italian Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype. In particular, our ultimate goal was to identify the region(s) of the fibrillin 1 (FBN1) gene mainly involved in the health of the heart and of the aorta in terms of the cardiovascular system. We searched for a molecular defect in three patients with classic Marfan syndrome (MFS). The mutations were detected applying heteroduplex analysis to each of the 65 exons of the FBN1 gene amplified by polymerase chain reaction (PCR). Exons containing heteroduplex bands were sequenced directly from PCR products. This study reports the detection of three unique missense mutations in the FBN1 gene in three Italian patients: a 44-year-old adult male and 36-year-old female affected by classic MFS (with all the cardinal manifestations in the cardiovascular, ocular and skeletal systems), and an 11-year-old male affected by infantile (earlier onset) classic MFS. The first two are sporadic cases and present a Cys-->Arg amino acid substitution (T-->C substitution at nucleotide 7729) in exon 62 and a Cys-->Tyr amino acid substitution (G-->A substitution at nucleotide 6695) in exon 54. The third is a familial case which presents a Cys-->Trp aminoacidic substitution (C-->G substitution at nucleotide 3546) in exon 28. Our data confirm that cysteine substitutions in calcium binding epidermal growth factor (cbEGF)-like domains cause severe Marfan phenotype. Exon 24-32 cluster seems to produce an even more severe phenotype. The early characterization may be of clinical relevance for prevention and early surgical treatment of aortic aneurysm or dissection.

Adult↗
PubMed1997

Tissue factor and plasminogen activator inhibitor type 2 expression in human stimulated monocytes is inhibited by heparin.

Stimulated monocytes are involved in blood clotting and fibrin dissolution by synthesizing tissue factor (TF) and fibrinolytic components such as plasminogen activator inhibitor type 2 (PAI-2). Heparin interacts with smooth muscle cells, platelets, and endothelial cells and specifically binds to human monocytes. In endothelial and smooth muscle cells, heparin selectively inhibits collagenase and tissue plasminogen activator gene expression. To investigate (1) heparin's influence on the hemostatic system by its interactions with plasma factors and cellular elements and (2) to determine its effects on gene expression in blood circulating cells, we studied the effect of heparin on TF and PAI-2 protein and mRNA in human lipopolysaccharide (LPS)- or interferon-gamma (IFN-gamma)-stimulated monocytes. TF and PAI-2 proteins were investigated by ELISA and by assaying procoagulant activity. The mRNA study was carried out by an initial PCR screening followed by a Northern blot semiquantitative analysis. Heparin (0.5 U/mL) inhibited both TF and PAI-2 production and gene expression. The contemporaneous protein and mRNA decrease (TF and PAI-2 protein 22 and 42%, respectively; suggests that this action is, at least partially, at the transcriptional level. The effect is not specific for heparin and is not demonstrated by other glycosaminoglycans (chondroitin-4-sulfate or dermatan sulfate). This action may be relevant for the antithrombotic activity of heparin in cell-mediated blood clotting activation.

Anticoagulants↗
PubMed1997

Prevalence of factor V Leiden mutation in non-European populations.

A difference in the prevalence of venous thromboembolism (TE) in major human groups has been described and an uneven distribution of FV Leiden mutation over the world has recently been reported. We investigated FV Leiden mutation in 584 apparently healthy subjects mostly from populations different from those previously investigated: 170 Europeans (Spanish, Italians), 101 sub-saharan Africans (Fon, Bariba, Berba, Dendi), 115 Asians (Indonesians, Chinese, Tharus), 57 Amerindians (Cayapa), 84 Afroamericans (Rio Cayapa, Viche), and 57 Ethiopians (Amhara, Oromo). The mutation was detected in only 1/115 Asian (Tharu) and in 5/170 Europeans (4 Italians, 1 Spanish). These data confirm that in non-Europeans the prevalence of FV mutation is at least 7 times lower than in Europeans and provide indirect evidence of a low prevalence not only of the FV Leiden gene but also of other genes leading to more severe thrombophilia. Finally, findings from the literature together with those pertaining to this study clearly show a marked heterogeneity among Europeans.

Africa South of the Sahara↗
PubMed1995

Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes.

The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1 cytokine profile, but none of seven Th2 clones, induced TF production and PCA. T-cell blasts from four Th1 activated clones were fixed with paraformaldehyde and added to monocytes in the presence of medium alone or their supernatants. Addition of either fixed Th1 cells or their supernatants induced low TF production (0.2 to 0.6 ng/mL), whereas addition of both resulted in much higher TF synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only interferon-gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4 ng/mL). No TF synthesis was induced by activated and fixed Th2 cells and/or their supernatants, whereas combined addition of fixed Th2 cells and Th1 supernatants or IFN-gamma induced noticeable TF production. The addition of either anti-IFN-gamma antibody or Th2 supernatants to monocytes stimulated with activated and fixed Th1 cells plus their supernatant resulted in a dose-dependent inhibition of TF synthesis, which was partially restored by neutralization of interleukin-4 (IL-4) or IL-10. Addition of recombinant IL-4, IL-13, or IL-10, but not IL-5, inhibited the Th1-induced TF production by monocytes. Data indicate that both CD8+ and CD4+ Th1, but not Th2, T cells can help TF production and PCA. Both cell-to-cell contact with activated T cells and Th1-type cytokines, in particular IFN-gamma, are required for optimal TF synthesis, whereas Th2-derived cytokines (IL-4, IL-13, and IL-10) are inhibitory. This may be of potential interest for future therapeutic strategies.

Antigens↗