Search PubMed⌕ Search

Biomedical subjects

G De Gaetano

Publications and source records attributed to G De Gaetano.

At least 19 recordsLinked to original sources

Alcohol-free red wine prevents arterial thrombosis in dietary-induced hypercholesterolemic rats: experimental support for the 'French paradox'.

The concept of the 'French paradox' has been recently challenged. As it is difficult in a short period to produce direct clinical evidence of the protective effect of red wine on thrombosis, we evaluated such a possibility in an experimental model mimicking the conditions of the 'French paradox'. Normolipidemic rats (FNL) were fed a standard diet or a 2% cholesterol-rich-diet (Ch-rich-diet) for 5 months: the latter was given either alone (FNL + D) or in combination with 'alcohol-free' red wine (FNL + D + 5 W). Arterial thrombosis was measured as the occlusion time (OT) of an artificial prosthesis inserted into the abdominal aorta. Lipid levels, platelet adhesion to fibrillar collagen, factor VII (FVII) clotting activity and fibrinogen levels were also measured. Compared to animals fed a standard diet, Ch-rich diet induced in FNL rats a several-fold increase in lipids and FVII levels with a concomitant significant increase in both thrombotic tendency (shortening of the OT) and platelet adhesion. 'Alcohol-free' red wine supplementation almost completely reverted the prothrombotic effect of the Ch-rich-diet. Indeed, the OT was prolonged from 78 +/- 3 to 122 +/- 10 h (P < 0.01), while platelet adhesion to fibrillar collagen was reduced from 49 +/- 3.5% to 30 +/- 2.8%. Neither the increase in lipid levels induced by Ch-rich diet nor FVII or fibrinogen levels were modified by wine supplementation. In conclusion, in experimental animals, this study supports the concept of the 'French paradox' that regular consumption of wine (rather than alcohol) was able to prevent arterial thrombosis associated with dietary-induced hypercholesterolemia, an effect mediated by downregulation of platelet function.

Animals↗

Aspirin.

Explore the source record for details and available documents.

Aspirin↗

Resveratrol and quercetin down-regulate tissue factor expression by human stimulated vascular cells.

BACKGROUND: Epidemiological studies have shown that consumption of wine reduces the risk of coronary heart disease. Resveratrol and quercetin, two polyphenolic compounds found in grapes and red wine, have been shown to contribute to this protection by exerting several biological properties which could be associated with cardioprotection. Tissue factor (TF), the cellular receptor that initiates blood coagulation, plays a primary role both in hemostasis following tissue injury and in the pathogenesis of atherosclerosis which predisposes to thrombosis. OBJECTIVES: We investigated the role of resveratrol and quercetin on TF expression by endothelial and mononuclear cells (MN). METHODS: Confluent human umbilical vein endothelial cells and MN collected from healthy donors were stimulated with bacterial lipopolysaccharide, interleukin-1beta or tumor necrosis factor-alpha after incubation with increasing concentrations of resveratrol or quercetin. RESULTS: In both cell types, TF activity induced by any agonist was significantly reduced by resveratrol or quercetin in a dose-dependent fashion. Northern blot analysis indicated that resveratrol and quercetin strongly reduce TF mRNA in both cell types. The inhibition of TF mRNA originated from a reduction in nuclear binding activity of the transacting factor c-Rel/p65, which was induced by the agonists and measured by electromobility shift assay. Western blot analysis revealed that the diminished c-Rel/p65 activity was dependent upon inhibition of degradation of the c-Rel/p65 inhibitory protein IkappaBalpha. CONCLUSIONS: These results provide a molecular basis which could help explain the protective activity of red wine against cardiovascular disease.

Active Transport, Cell Nucleus↗

A high-score Mediterranean dietary pattern is associated with a reduced risk of peripheral arterial disease in Italian patients with Type 2 diabetes.

BACKGROUND: The 'Mediterranean diet' is considered to exert protective effects on cardiovascular disease, although a wide range of dietary patterns exists among subjects living even in the same Mediterranean country. OBJECTIVE: To investigate the association between specific dietary patterns and peripheral arterial disease (PAD) in Italian Type 2 diabetes patients. DESIGN: From a cohort of 944 patients with Type 2 diabetes, 144 patients with PAD were selected, and matched for age and sex with 288 Type 2 diabetic control patients without macrovascular complications. A dietary score was elaborated from a semiquantitative food frequency questionnaire. The higher the final score, the healthier the eating habit. RESULTS: In multivariate analysis, a higher score was independently associated with a significant reduction in PAD risk [odds ratio (OR) = 0.44; 95% confidence interval (CI) 0.24, 0.83]. Diabetes duration (OR > 15 years = 2.49; 95% CI 1.45, 4.25), hypertension (OR = 2.12; 95% CI 1.31, 3.45) and butter consumption (OR = 2.6; 95% CI 1.15, 3.68) were also significantly associated with PAD. The dietary score significantly improved the predictive value of models based on duration of diabetes and hypertension. (LSR = 2.19, DF = 7, P < 0.001). The effect of a high dietary score on the risk of PAD was independent of diabetes duration and hypertension. CONCLUSION: In Italian Type 2 diabetics, a higher dietary score has a protective role against PAD. The use of butter increases the risk of PAD even in patients regularly consuming olive oil. Dietary advice may be helpful for the prevention of PAD in diabetics even in populations traditionally accustomed to a Mediterranean dietary habit.

Aged↗

Aortic valve reconstruction associated to ascending aorta tubular graft replacement in aortic incompetence by annuloaortic ectasia.

OBJECTIVE: Aortic valve incompetence associated with severe aortic ectasia is usually treated by aortic valve and ascending aorta replacement. In cases of isolated aortic ectasia or in Type A aortic dissection the valve is often normal and the incompetence is just due to annular dilatation. Such conditions lead to the application of various valve-sparing surgical techniques, as described by Senning et al., showing the advantages of preservation of the native valve, but the disadvantage of a high technical complexity and a high incidence of recidivation. METHODS: We describe a valve-sparing surgical procedure, which has the advantage of a direct and simple approach together with satisfying mid-term results. After the aortic bulb has been fully transected, the excessive wall tissue is resected by two or three triangular excisions just above the valve commissures. Wall excision was indicated in those patients with an aortic diameter exceeding 65 mm at the sino-tubular junction. Tissue excision should not exert tension on to the coronary ostia or excessively reduce aortic diameter. Three external Teflon strips, overriding each other, are placed around the aortic bulb and are included in the direct suture of the edges of the triangular excisions. They are fixed by a running suture over the free border of the bulb. Aortic valve commissures are resuspended when needed. In this way, the aortic bulb, with a competent valve, is wrapped in a prosthetic and inextensible graft. The aortic continuity is then re-established with the interposition of a tubular dacron graft. RESULTS: From April 1990 to December 1995, 21 patients (mean age 48 years, range 32-70) scheduled for surgery for aortic valve incompetence associated with annuloaortic ectasia were treated with this technique. In one patient the procedure failed to achieve a satisfying valve competence and the valve was replaced. In another case a prolapse of the non-coronary cusp required reoperation with aortic valve replacement, without further complications. At follow-up time (mean 42 months, range 18-78), all patients were well and healthy, with control echoes showing no residual valve incompetence and with invariate bulb diameters at every successive examination. CONCLUSIONS: Our experience shows that this new valve-sparing approach allows safe and persistent correction of aortic valve incompetence and annuloaortic ectasia although longer term follow up is needed.

Aorta↗

Combined aortic valve replacement and left ventricular aneurysm plication in systemic lupus erythematosus.

The case of a 37-year-old female patient is reported with systemic lupus erythematosus and severe renal function impairment, and associated aortic insufficiency, obstructive coronary disease and aneurysm of the left ventricular inferior free wall. Renal failure, hematologic disorder and the need for high-dose steroid therapy to control the autoimmune disease were considered the main surgical risks. Surgery included aortic valve replacement and plication of the ventricular aneurysm. The postoperative course was free of any major complications related to surgery or SLE disease.

Adult↗

Prostacyclin is required for t-PA release after venous occlusion.

The role of vascular cyclooxygenase pathway on tissue-type plasminogen activator (t-PA) release after venous occlusion was studied in anesthetized rats. After the inferior vena cava was clamped for 30 min, fibrinolytic activity increased from 143.7 +/- 14.5 to 209.5 +/- 10.3 mm2 (mean +/- SE, P < 0.002). This increase was prevented by aspirin at high (100 mg/kg i.v.) but not at low doses (1 mg/kg i.v.). Dazoxiben (10 mg/kg i.v.), an inhibitor of thromboxane synthase, was ineffective on the fibrinolytic response. Both the basal levels of 6-ketoprostaglandin F1 alpha and its increase after venous occlusion were suppressed by 100 mg/kg aspirin administration (from 0.64 +/- 0.2 to 0.05 +/- 0.002 ng/ml before occlusion, P < 0.001; and from 1.08 +/- 0.2 to 0.06 +/- 0.002 ng/kg after occlusion, P < 0.001), whereas they were both unaffected by aspirin at low doses (from 0.53 +/- 0.06 before to 1.20 +/- 0.08 ng/ml after stasis). Moreover, iloprost, a stable analogue of prostacyclin, reversed the aspirin inhibitory effects on fibrinolytic activity by restoring t-PA vascular release after venous stasis. Our results provide experimental evidence that an intact cyclooxygenase pathway in vascular wall is required for the fibrinolytic activity increase after venous occlusion in rats.

6-Ketoprostaglandin F1 alpha↗

[Predictive value of the shunt-to-infarct size ratio as a surgical risk factor in patients with decompensated post-ischemic interventricular septal rupture].

Postischemic septal rupture has always been evaluated, in respect of surgical indication, as regards the time lapse between infarct and rupture, interval between rupture and operation, extension of myocardial damage and general risk factors such as age, sex and associated pathologies. But in fact the surgeon is dealing with a two sided problem, the MI and the rupture, and thus surgical results depend upon both the residual ventricular function after MI and the consequences of volume overload on a damaged muscle. Surgical indication could not be based on a single criterion only. Extension of the MI alone is not fully predictive of operative mortality because, aside the reperfusion injury, the repair further jeopardizes viable myocardium and alters ventricular geometry; although the shunt appears unrelated to mortality it certainly interferes with operative outcome at least because of the time elapsed between rupture and repair. So far an index which could correlate the extension of myocardial damage and the entity of the shunt with each other was not available. Patients with septal rupture follow an emergency protocol and are often insufficiently investigated but every patients has a least one echo-Doppler evaluation or even a ventriculography while one or more ECGs are always available. With the presumption that the Qp/Qs is roughly indicative of the right ventricular volume overload and that ecg signs of myocardial infarct are always reliable, we have reviewed among our 24 patients with septal rupture those where a full ecg tracing and a quantitative Echo or angiographic evaluation of the shunt were available.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Doppler echocardiographic evaluation of the new mechanical bileaflet Sorin Bicarbon valve prosthesis compared with St. Jude Medical].

BACKGROUND: Despite the Bicarbon valve has been marketed for more than two years, no systematic Doppler evaluation of its normal functioning has yet been published. Therefore, the aims of this study were to establish the normal flow characteristics for the Bicarbon bileaflet prosthetic heart valve and to compare them with those obtained from the St. Jude Medical valve prosthesis. METHODS: Doppler echocardiographic characteristics of normally functioning Bicarbon prostheses were prospectively assessed in 76 consecutive patients (44 males and 32 females, mean age 60 +/- 10 years) with 79 valves in mitral (n = 29) and aortic (n = 50) position whose function was considered normal by clinical and echocardiographic evaluation. In addition, Doppler characteristics of the Bicarbon valves in aortic position were compared to those of 27 normal functioning St. Jude Medical implanted during the same period. RESULTS: For the mitral valve prostheses, we found non significant difference among prosthesis sizes in terms of transprosthetic gradients or pressure half time. Peak and mean gradients were similar in the 27-mm and 31-mm size valves (from 11 +/- 4 to 11 +/- 2 mm Hg and from 5 +/- 2 to 5 +/- 1 mm Hg, respectively; p = NS for both). Similarly, the pressure half time was similar in the 27-mm and in the 31-mm size valve (85 +/- 16 and 76 +/- 13 msec; p = NS). Conversely, for the aortic valve prostheses, there was a significant decrease in transprosthetic gradients and an increase in effective orifice areas as prosthesis size increased. Mean gradient was 13 +/- 1 mm Hg in 19-mm size valves, and it decreased to 6 +/- 2 mm Hg in the 29-mm size. Effective prosthetic valve area calculated using the continuity equation, ranged between 1.0 +/- 0.3 cm2 for 19-mm size valves to 3.5 +/- 0.7 cm2 for 29-mm size. With analysis of variance, effective prosthetic aortic valve area differentiated various valve sizes (F = 23.3; p < 0.0001) better than peak (F = 3.2; p = 0.017) or mean (F = 4.19; p = 0.0035) gradients alone did. Furthermore, effective prosthetic aortic valve area correlated better than peak and mean gradients with prosthetic size (r = 0.87, r = -0.58 and r = -0.57; respectively). In addition, peak and mean transprosthetic gradients and effective prosthetic aortic valve areas did not show any statistically significant difference between the Bicarbon and the St. Jude Medical valves in aortic position, either in 19 and 21 mm (25 +/- 8 mm Hg, 13 +/- 4 mm Hg, 1.3 +/- 0.3 cm2 and 32 +/- 11 mm Hg, 17 +/- 6 mm Hg, 1.2 +/- 0.4 cm2, respectively; p = NS), or in 23 and 25 mm (21 +/- 8 mm Hg, 11 +/- 4 mm Hg, 2.1 +/- 0.5 cm2 and 24 +/- 11 mm Hg, 12 +/- 5 mm Hg, 1.8 +/- 0.4 cm2, respectively; p = NS) or in 27 and 29 mm (12 +/- 2 mm Hg, 7 +/- 1 mm Hg, 2.8 +/- 0.9 cm2 and 16 +/- 5 mm Hg, 7 +/- 2 mm Hg, 2.6 +/- 0.4 cm2, respectively; p = NS). CONCLUSIONS: This study suggest that the Bicarbon valve prosthesis offers relatively little resistance to forward flow except at a small anulus diameter. Furthermore, these is no statistically significant difference between the Bicarbon and the St. Jude Medical in aortic position with regard to early hemodynamic performances.

Aged↗

Antiplatelet activity of 2-(6-carboxyhexyl)-3-n-hexylcyclohexylamine (IBI P-05006), a thromboxane receptor antagonist.

2-(6-Carboxyhexyl)-3-n-hexylcyclohexylamine (IBI P-05006) is a molecule with cytoprotective and antisecretory actions. Since its chemical structure resembles that of the prostanoid nucleus of thromboxane (Tx) A2, the possibility of antiplatelet activity was investigated. The aims of our study were to evaluate a possible inhibitory effect of IBI P-05006 on in vitro platelet aggregation induced by different stimuli and to characterize its mechanism of action. For this purpose, selected mechanisms of platelet function were evaluated. IBI P-05006 inhibited platelet aggregation induced by arachidonic acid or U46619, at concentrations ranging from 0.4 to 4 microM, dose dependently, without interfering with arachidonic acid metabolism. The possibility that the compound acts through adenylate cyclase stimulation was ruled out by measurement of cAMP levels, which were not increased. Receptor binding studies indicated competitive inhibition by IBI P-05006 of the binding of the ligand [3H]SQ29548 to the TxA2/(prostaglandin) PG-cyclic endoperoxides receptor with IC50 in the range of concentrations active on platelet aggregation. In conclusion, IBI P-05006 inhibits in vitro human platelet aggregation through a specific mechanism of competition for the TxA2/PG-cyclic endoperoxides receptor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Current concepts of platelet physiopathology.

The genesis of the modern concept of platelet physiopathology can be traced historically to many individuals and developments, including the pioneering work of Giulio Bizzozero over 100 years ago. Much knowledge has since been gained to the point that we can now define many of the elements of the platelet function in relation to the hemostatic process in terms of their molecular biology. This presentation will attempt to synthesize a simple, understandable, yet global perspective of platelet function and of its participation to the pathogenesis of arterial thrombosis. Focus will be placed on the crucial importance of cell-cell interaction. A symbolic representation of platelet plug formation using simple mathematical figures like the line, point, and triangle is helpful. The line represents the vascular system with intact endothelial cell linings. The irritation/disruption of vascular endothelium can be viewed as a point on the line representative of a localized event. From this initial (often small) stimulus, amplification occurs rapidly to produce an appropriate cellular and humoral response, represented by a triangle. Each component (vessel wall, platelets, leukocytes, coagulation and fibrinolysis systems) of this complicated response has biological characteristics which localize and amplify subsequent reactions to the site of primary injury until bleeding is arrested and the wound is healed or arterial thrombosis progresses to vascular occlusion.

Arteriosclerosis↗

[Doppler echocardiographic evaluation of functional parameters of mechanical and biological valve prostheses].

We studied and compared functional parameters in 314 valvular prostheses. The following parameters have been calculated: mean transvalvular gradients for aortic and mitral prostheses and functional area by Pht (pressure half time) for mitral prostheses. All patients with important depression in myocardial function, tachycardia or malfunctioning prostheses were excluded. 173 prostheses were in aortic position and 141 in mitral position. Mitral prostheses were: 31 biological and 110 mechanical. We subdivided mechanical prostheses in monoleaflet (Omnicarbon, Sorin-Carbocast and Allcarbon, Medtronic, Bjork-Shiley) and bileaflet (Sorin-Bicarbon, St. Jude). These three groups were compared: mean transvalvular gradients and area showed no differences. Aortic prostheses were: 33 biological and 140 mechanical; mechanical prostheses were subdivided in two groups: monoleaflet (Sorin Allcarbon e Carbocast, Bjork-Shiley, Medtronic, Omnicarbon) and bileaflet (Sorin-Bicarbon, St. Jude). Mean transvalvular gradients of these three groups were compared within each group for every size: bileaflet prostheses demonstrated inferior gradients than biological and monoleaflet for 19-21 and 23 sizes; in superior sizes there were no significant differences. Further analysis showed a significant correlation among gradients and body surface area in the 21 size prostheses (p = 0.004). Bileaflet prostheses in this subgroup showed less increase in mean gradient with surface area than mechanical and biological ones.

Aortic Valve↗

Inhibition by heparin of platelet activation induced by neutrophil-derived cathepsin G.

Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombotic activity of this drug. The present study shows that different heparin preparations (50 nM) completely prevent human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil-derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an inactivated active for antithrombin III was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade of protease activity. Heparins were also shown to reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used to optimize its antithrombotic efficacy.

Amino Acid Sequence↗

Ten years of surgery of aortic dissections and aneurysms. Clinical experience and original contributions.

From January '82 to April '91, 117 patients with aortic disease were operated upon at our University Hospital in Genoa, Italy. Thirty-seven had arch dissections or aneurysms; 66 had acute aortic dissection type A and 14 had aortic dissections or aneurysms type B, acute and chronic. Patients with arch or type B aortic pathology but without surgical indication and cases of post-traumatic aortic transections are not included. There were 84 male and 33 female patients with a mean age of 52 (6 min and 74 max). In the acute patients, the mean interval between clinical onset and surgery was 34 hours (6 min-72 max). All patients with primary arch disease had surgical repair with the aid of deep hypothermia and circulatory arrest (17-96 min). Type A dissections were treated with standard CPBP at 28 degrees C. Surgical techniques included direct suture of intimal tear alone, direct suturing of the two aortic stumps; interposition of Dacron tubular prosthesis; Bentall repair; separated valve and aortic replacement; an original aortic bulb aortoplasty with valve repair; arch replacement with resuturing of one or more aortic trunks. Human fibrin glue (Tissucol) was employed either as haemostatic agent, widely spread over the suture lines or as tissue adhesion agent between dissected aortic layers. Human fibrin glue is adopted because it gathers high glueing capacity and maintenance of the elastic property of the vessel wall. Hospital mortality (30 days) has been 25% in ascending aortic dissections (16/66 patients) and 50% in patients with arch disease (18/37 patients) who needed circulatory arrest. Late mortality 5/83 (6%). Reoperations for aortic valve insufficiency or re-dissection have been 7 (8.4%). Early diagnosis (increasing reliability of 2D-Echo and CT scans), aggressive surgery, meticulous myocardial and cerebral protection and introduction in clinical use of biological glues seem to be the milestones of present and further improvements in surgical results.

Acute Disease↗

Coronary occlusion secondary to blunt chest trauma: a first attempt at balloon angioplasty.

There have been only 58 angiographically documented reports of transmural myocardial infarction due to closed-chest trauma. None of these cases has been treated by percutaneous transluminal coronary angioplasty. We report the case of a 40-year-old man who developed an anterior-wall myocardial infarction secondary to blunt chest trauma suffered in an automobile accident. Angiographic study performed 2 months after the injury revealed an isolated total obstruction of the left anterior descending coronary artery. The patient was judged a good candidate for balloon angioplasty, but total reocclusion occurred within 24 hours of the procedure and a 2nd attempt did not restore patency. Surgical revascularization was performed a week later. A year after his injury, the patient remains asymptomatic and is back at work. Despite the failure of percutaneous transluminal coronary angioplasty in its 1st application to coronary artery repair after blunt chest trauma, we believe it to be the treatment of choice in young patients and in single-vessel disease.

Journal Article↗