Biomedical subjects

G M Puddu

Publications and source records attributed to G M Puddu.

At least 19 recordsLinked to original sources

PubMed2001

HMG-CoA reductase inhibitors: Is the endothelium the main target?

Endothelial dysfunction is an early event in atherosclerosis and could be considered a response to the injury induced by major risk factors. There is evidence that endothelial dysfunction is intimately involved in the onset and the progression of cardiovascular disease through abnormalities in the production, release or degradation of endothelium-derived factors, mainly nitric oxide and endothelin 1. Several reports have shown that drugs of the statin class could have multiple beneficial effects related to endothelium-mediated vasoactive, antithrombotic, antiproliferative and anti-inflammatory actions. Thus, the question arises of whether endothelial cells are the main target of statin therapy, in the setting of both hypercholesterolemia and normocholesterolemia. Experimental and clinical studies are reported that could support this hypothesis.

Animals↗

PubMed2001

Current thinking in statin therapy.

The HMG-CoA reductase inhibitors (statins) are now considered the most potent lipid-lowering drugs. Treatment with statins reduces both morbidity and mortality rates due to coronary artery disease. There is now increasing evidence that the clinical benefits obtained with statins cannot be solely attributed to a decrease in low-density lipoprotein (LDL) level. These drugs may also have beneficial effects on endothelial dysfunction, LDL oxidation, rheological and thrombogenic factors, cellular inflammation and plaque formation and stability. Further, there are differences among the various statins on these non-lipid variables. The biochemical effects of statins, as well as their clinical benefits, should be taken into consideration.

Cholesterol, LDL↗

PubMed2000

Endothelial dysfunction in hypertension.

Endothelial cells release both relaxing and contracting factors that modulate vascular smooth muscle tone and also participate in the pathophysiology of essential hypertension. Endothelium-dependent vasodilation is regulated primarily by nitric oxide but also by an unidentified endothelium-derived hyperpolarizing factor and by prostacyclin. Endothelium-derived contracting factors include endothelin-1, vasoconscrictor prostanoids, angiotensin II and superoxide anions. Under physiological conditions, there is a balanced release of relaxing and contracting factors. The balance can be altered in cardiovascular diseases such as hypertension, atherosclerosis, diabetes and other conditions, thereby contributing to further progression of vascular and end-organ damage. In particular, endothelial dysfunction leading to decreased bioavailability of nitric oxide impairs endothelium-dependent vasodilation in patients with essential hypertension and may also be a determinant for the premature development of atherosclerosis. Different mechanisms of reduced nitric oxide activity have been shown both in hypertensive states and several cardiovascular diseases, and endothelial dysfunction is likely to occur prior to vascular dysfunction. Thus, the strategies currently used to improve endothelial dysfunction may result in decreased morbidity and mortality in hypertensive patients.

Angiotensin II↗

PubMed1998

Relationship between serum C3 levels and traditional risk factors for myocardial infarction.

OBJECTIVE: Serum C3, a complement component produced by macrophages, the liver and the adipose tissue, is associated with the risk of myocardial infarction in men. This study was performed to ascertain the relationships between serum C3 and traditional risk factors in an unselected population sample. METHODS AND RESULTS: A random population of 1,068 subjects (537 men and 531 women, 23 to 90 years old) was examined for risk factor assessment. Serum C3 was measured by nephelometry. C3 was independently associated with body mass index (P < 0.0005, especially in women), LDL-cholesterol (P = 0.0014 in men and 0.0215 in women), systolic blood pressure (P < 0.05) and, in women, with triglycerides (P = 0.0133) and blood glucose (P = 0.0383), as assessed by multivariate analysis (multiple linear regression). The overall R2 were 0.07 and 0.21 for men and women, respectively. Women over 50 years of age had significantly higher C3 levels, LDL-cholesterol and body mass index than younger women. The correlation of C3 with LDL-cholesterol was present after the age of 40 in men, and 2 decades later in women. CONCLUSIONS: These data show that serum C3 correlates with a cluster of conventional risk factors for myocardial infarction resembling insulin resistance. Such correlations may be either independent of, or mediated by the development of coronary atherosclerosis.

Adult↗

PubMed1998

The shape of enzymatic curves during acute myocardial infarction: relationship to the progression of necrosis and implications for thrombolysis.

BACKGROUND: During acute myocardial infarction, the ascending branch of creatine kinase curves has a sigmoidal course whose inflection point marks the maximum rate of enzymatic increase in serum. This study was performed to assess the relationship between these morphologic characteristics of creatine kinase curves and the progression of myocardial necrosis. METHODS AND RESULTS: In isolated rat hearts exposed to different degrees of ischemia (coronary flow of 0.6 or 0.2 ml/g/min), the total quantity of creatine kinase released in the effluent had a sigmoidal course similar to the ascending branch of the curves from patients with acute myocardial infarction. Other rat hearts were frozen (which causes maximum damage to cell structures), thawed and then perfused. The resulting enzymatic curves had a downward concave ascending trend, similar to the portion beyond the inflection point of sigmoidal curves (the rate of creatine kinase release was maximum at the onset of perfusion and then decreased progressively). Finally, in some experiments ischemic rat hearts were further damaged by the perfusion, at different times, with highly concentrated catecholamines and without oxygen and substrates. This damaging perfusate was able to increase the rate of creatine kinase release (p = 0.0001) only when it was started before the inflection point of enzymatic curves. In 25 creatine kinase curves from patients with acute myocardial infarction (19 men and 6 women, age range 42 to 68 years), who were not treated with thrombolysis, the time of inflection varied from 1 to 12 hours from the onset of symptoms, with a maximum frequency between the 7th and the 8th hour. CONCLUSIONS: Based on these data, a biological model with 3 compartments has been suggested to explain the shape of creatine kinase curves, according to which the inflection point would occur after the completion of myocardial necrosis. The variability of the time of inflection might account for the cases of beneficial late thrombolysis reported in literature.

Adult↗

PubMed1997

Blood pressure and intellectual function in elderly subjects.

OBJECTIVE: to assess the relationship between hypertension and cognitive function in elderly subjects. METHODS: 17 subjects with uncomplicated hypertension (nine male, eight female) and 27 control subjects with similar educational level and age (18 male, nine female) were studied. These individuals were recruited, according to strict selection criteria, from a random sample of 120 elderly subjects living in the community, who had a normal Mini Mental State score. An extensive neuropsychological test battery, sensitive to mild cognitive impairment, was administered in standard conditions to measure attention, concentration and judgement, psychomotor speed, memory and learning. Affective disorders were also evaluated. In all patients a computed tomography scan was performed. RESULTS: subjects with high blood pressure had lower mean levels of performance in attentional measures; tapping test (inhibition of incorrect answers), three words-three shapes test (attempts; incidental memory) and reaction time to multiple stimuli. They also scored worse in clusters 1 and 2 of the Hamilton rating scale for depression. Confluent white matter lesions were found in nine hypertensive subjects (52.9%) and five controls (18.5%; P = 0.0170). Lacunes were demonstrated in 11 hypertensive (64.7%) and four normotensive people (14.8%; P = 0.0007). In a multivariate analysis (logistic regression), three cognitive variables (tapping, Hamilton cluster 2 and Hamilton total score) remained significantly associated with hypertension, independently of the presence of cerebral lesions. CONCLUSIONS: in elderly otherwise normal hypertensive subjects, an attentional impairment may occur, which appears to be functional and possibly reversible rather than structural and progressive.

Aged↗

PubMed1996

Silent lacunar infarcts in elderly patients with chronic non valvular atrial fibrillation.

It is still debated whether non valvular atrial fibrillation (NVAF) may be responsible for "silent" lacunar lesions. The aims of our study were to compare the prevalence of subcortical lacunar infarctions in highly selected elderly subjects with or without NVAF, and to investigate the positive relationship of such lesions to the impairment in cognitive and physical functions. Thirty-eight patients with NVAF (mean age 80.6 years) were compared with 40 patients in sinus rhythm (mean age 80.4 years). Exclusion criteria were previous stroke or transient ischemic attacks, significant lesions of extracranial arteries, and any previous disease leading to cognitive impairment or potentially interfering with cognitive functions. A cranial computed tomogram was performed in every case, and the number of lacunae was recorded. Cognitive status and mood were assessed by means of Mini Mental Status Examination and the Geriatric Depression Scale, respectively. The number of impaired basic and instrumental activities of daily living (BADL e IADL) was also recorded. A significantly higher percentage of patients with lacunar lesions was detected in the NVAF group. The MMS score was lower in these patients, but did not reach significant levels. In univariate analysis, the presence of lacunae was found to be significantly associated with age, systolic blood pressure and atrial fibrillation, but, in a multiple logistic regression model, only age and atrial fibrillation retained a significant association. Similarly, in univariate analysis, a low MMS score was found to be related to age, systolic blood pressure, leukoaraiosis and both the presence and the number of lacunar lesions. In multivariate analysis, only age and the number of lacunae were significantly associated with a low MMS. It is concluded that in elderly patients NVAF is associated with subcortical ischemic lesions which may contribute to the impairment of cognitive function.

Aged↗

PubMed1996

[Clinical aspects and pathogenetic mechanisms of cognitive impairment in arterial hypertension].

Arterial hypertension may be responsible for cognitive impairment indirectly, by means of ischemic or haemorrhagic cerebral lesions. In this regard multi-infarct dementia, subcortical dementia due to "small vessel disease" and Binswanger's syndrome are the clinical pictures more commonly observed. However also in hypertensives free from cerebrovascular events, dysfunctions in memory, attention, abstract reasoning, mental flexibility and psychomotor abilities have been found. The pathogenesis of these findings is uncertain. Small cerebral asymptomatic lesions (lacunae, leukoaraiosis) could disconnect the cortical and subcortical structures in the brain; however other factors, such as global or regional reductions of cerebral blood flow or disturbances in neurotransmitters release cannot be ruled out. The effects of anti-hypertensive therapy are conflicting, some authors reporting an improvement and others a worsening of cognitive performances. In the elderly the risk linked to hypertension may be increased by several predisposing factors and therefore this condition must be considered with attention as a pathogenetic factor of senile dementia.

Aged↗

PubMed1995

Association of serum C3 levels with the risk of myocardial infarction.

PURPOSE: Serum complement and IgA levels have been found to be retrospectively associated with the presence of diffuse atherosclerosis. This study was performed to assess whether serum immunoglobulins and complement components are predictive of future ischemic events. PATIENTS AND METHODS: The baseline values of IgG, IgA, IgM, C3, and C4 were measured in the sera from a cohort of 860 inhabitants of the town of Brisighella, Italy. They were 444 men and 416 women, mean age 53.9 years (SD 12.4, range 23 to 84), who had not had any ischemic events (myocardial infarction [MI], angina pectoris, stroke, transient ischemic attack, or intermittent claudication) at the time of blood sampling in 1984. Their baseline values for the main recognized risk factors for atherosclerosis were known at baseline and for 4 years of follow-up. Multiple logistic regression analysis was performed for associations between ischemic events and immunologic variables (including serum IgG, IgA, IgM, C3, and C4) and risk factors for atherosclerosis (including age, sex, diastolic blood pressure, cigarette consumption, Quetelet index, total cholesterol, HDL cholesterol, triglycerides and blood glucose). RESULTS: During follow-up, 57 subjects experienced ischemic events, including 28 cases of coronary heart disease (17 MI and 11 angina pectoris). Of the immunologic variables studied, only serum C3 was found to be independently associated with ischemic events (P < 0.005 for any ischemic events, coronary heart disease, and MI). The population was divided into thirds according to C3 values. The cumulative incidence of MI was 7.1/1,000 in the low third, 10.6/1,000 in the middle third and 40.8/1,000 in the high third (risk ratio for high versus middle plus low = 4.2 after adjustment for age and sex; 95% CI 1.5 to 11.7). A separate analysis for the sexes showed that serum C3 was a particularly powerful predictor of MI in men. Men whose C3 levels were in the top third had a 72.6/1,000 incidence of MI while the incidence in the rest of the male population was 6.2/1,000 (risk ratio 10.7 after adjustment for age; 95% CI 2.3 to 49.0). When similar analyses were performed for angina pectoris, stroke, and intermittent claudication, no significant increase in risk was found to be associated with serum C3. CONCLUSION: C3 levels measured in sera from male subjects without previous ischemic events are independently associated with the risk of MI.

Adult↗

PubMed1995

Complement components and fibrinogen: correlations and association with previous myocardial infarction.

Serum complement levels have been found to be predictive of myocardial infarction up to 4 years before the acute event. To assess whether they are a marker of a hypercoagulable state, the serum or plasma levels of C3, C4, C3a, C4a, C1 inactivator, antithrombin III, protein S, protein C, fibrinogen and tissue plasminogen activator were measured in 31 patients with previous myocardial infarction and 33 controls (all males, 40-60 years old). C3, C4 and fibrinogen (which share the common characteristic of being acute phase proteins) were correlated and were associated with previous myocardial infarction, although this association persisted only for C4 in multivariate analysis. None of the coagulative variables directly involved in the complement system differed significantly in the two groups.

Adult↗

PubMed1995

[Serum C3 as a screening factor in the primary prevention of myocardial infarct].

This study addresses the possible use of serum C3 (third component of the complement system) to select the subjects to be submitted to diet or drug therapy in the primary prevention of myocardial infarction. C3 is synthesized by macrophages, which are the main cells involved in atheroma formation, and an association between serum C3 and the risk of myocardial infarction has recently been found in the male sex. We have studied 332 men aged 45-75 years, who had no cardiovascular disease at any time before blood sampling. In their sera C3 measurement was performed by nephelometry. The 4 year follow-up was known for all of these subjects: in particular, 11 had a myocardial infarction. The average LDL cholesterol (LDL-C) levels in the whole population were rather high (162.2 +/- 45.8 (1 SD) mg/dl). As standard treatment criteria (A), those suggested for primary prevention by the National Cholesterol Education Program panel of experts were adopted: diet if LDL-C > or = 160 mg/dl, or LDL-C > or = 130 mg/dl + 2 additional risk factors; drugs if, after diet, LDL-C > or = 190 mg/dl, or LDL-C > or = 160 mg/dl + 2 risk factors. This scheme was compared with two models of treatment which included the measurement of serum C3. According to the first of such models (B), diet should be prescribed when C3 levels are within the high third of distribution (> or = 135 mg/dl) with LDL-C > or = 100 mg/dl, and drugs should be given if, after diet, serum C3 is > or = 135 mg/dl with LDL-C > or = 130 mg/dl. The second model based on C3 (C) is of combined type since, in addition to model B criteria, it also suggests to prescribe a diet if LDL-C > or = 190 mg/dl, while drugs should be given if, after diet, LDL-C levels persist > or = 190 mg/dl. The effect of diet has been simulated by assuming a 10% decrease in LDL-C levels. According to all of these criteria, the subjects to treat with diet with the models A, B and C would have been, respectively, 71, 27 (p < 0.0001 vs mod A) and 45% (p < 0.0001 vs mod A) of the whole population, including among them, respectively, 82, 82 and 100% of the future myocardial infarctions. After diet, according to the three models A, B and C -29, 20 (p = 0.0117 vs mod A) and 30% of the whole population should have been treated with drugs, including, respectively, 54, 64 and 82% of the future myocardial infarctions. In conclusion, the use of criteria based on serum C3, with respect to more traditional guidelines, might allow a more precise identification of the subjects to submit to diet and drug treatment in the primary prevention of myocardial infarction.

Aged↗

PubMed1994

Immunologic changes in circulating leukocytes in the presence of atherosclerotic disease.

To assess the numeric and functional changes in circulating white blood cells in the presence of severe atherosclerosis, 25 subjects with marked, angiographically assessed, atherosclerotic lesions and 29 selected controls were studied. Of the differential leukocyte counts, only monocyte count was significantly higher in the atherosclerotic than in the control subjects (449.0 +/- 115.6 (1 S.D.) vs. 344.1 +/- 138.8/mmc; P = 0.0016). By flow-cytometry no significant differences concerning monocyte surface antigens were found, except a feeble decrease in beta 2-microglobulin in the atherosclerotic subjects. As to lymphocytes, an increase in the CD8 population (33.4 +/- 6.8 vs 28.6 +/- 6.5%; P = 0.0144) and decreases in class I HLA antigen (96.6 +/- 7.3 vs 99.4 +/- 0.7%; P = 0.0049), beta 2-microglobulin (97.9 +/- 2.1 vs 99.3 +/- 1.0%; P = 0.0055) and especially in vivo DNA synthesis (3.8 +/- 1.2 vs 5.3 +/- 2.1%; P = 0.0102) percent expressions were found in the atherosclerotic patients with respect to the controls. This study shows that circulating monocytes are increased in atherosclerotic disease, possibly due to their participation in the phagocytosis of lipids in the arterial wall, with no further immunologic involvement. Conversely, the replicative activity of T lymphocytes is decreased, which might be a consequence of or a factor predisposing to atherosclerosis.

Acute Disease↗

PubMed1993

Increased serum IgA levels in subjects with previous myocardial infarction or other major ischemic events.

To ascertain whether the increase in serum IgA, which has been found to be associated with the presence of severe atherosclerotic disease, precedes or follows the occurrence of major ischemic events (MIE), we studied the serum levels of IgA as well as IgG and IgM in 145 subjects with acute or previous ischemic events and 34 controls. The subjects with previous myocardial infarction had higher IgA levels with respect to the controls, the patients with angina pectoris and those with acute myocardial infarction, while no significant differences concerning IgG and IgM were found. In the subjects with previous extracoronary events, immunoglobulin levels tended to be even higher. Overall, 30% of the subjects with previous MIE and only 3% of the controls had IgA levels over 4.5 g/l (p = 0.0018). This study indicates that total serum IgA is a marker of previous major ischemic events (protracted immune response to denatured proteins?), rather than a factor predisposing to atherosclerosis development.

Aged↗

PubMed1993

[Treatment of pulmonary embolism. Current status and future prospects].

Although still severe, the prognosis of pulmonary embolism has recently improved due to considerable progress in the therapeutic field. This paper concerns the various therapeutic tools, both pharmacologic and surgical, which are already available or under evaluation. Despite the introduction of thrombolytic drugs, heparin remains an indispensable drug. The rationale for its use comes from the need of preventing further clot formation, while endogenous fibrinolysis or thrombolytic drugs are dissolving the already existing clots. Thrombolytic drugs, such as streptokinase, urokinase or rt-PA, have changed the therapeutic strategy of pulmonary embolism, due to their ability to accelerate the normal fibrinolytic mechanisms and to facilitate pulmonary reperfusion. This often allows an early disappearance of symptoms and a reduced incidence of invalidating complications involving the respiratory function. rt-PA seems to be most effective and fast in inducing reperfusion (angiographic signs of clot dissolution are obtained in 82% of the patients within 2 hours). The administration of rt-PA by intravenous bolus has recently been proposed, which would induce an even faster thrombolysis and fewer hemorrhagic complications. The role of surgical therapy has declined after the diffusion of thrombolytic drugs, being reserved only for the most serious cases. When anticoagulation is counter-indicated or not effective, the prevention of embolic relapses can be achieved by percutaneous insertion of caval filters of different types. Some new catheters provided with rotating metallic tips, which allow the mechanical fragmentation of the emboli, are presently under evaluation. Although some improvements are needed, this technique is expected to become soon of general use, especially in cases in which thrombolytic therapy is counter-indicated.

Angiography↗

PubMed1992

[Association of serum C3 and essential hypertension].

This study was performed to assess the possible involvement of humoral immunity in essential hypertension, independently of the presence of atherosclerotic disease, which in turn may be associated with immunologic changes. Sixty-five patients without demonstrated atherosclerotic disease were selected according to clinical and arteriographic criteria, including 23 hypertensive subjects (all pharmacologically treated) and 42 controls. Mean ages (58.7 +/- 8.3(1 S.D.) years in the controls and 57.7 +/- 7.9 years in the hypertensive subjects) and sex distribution were similar in the 2 groups. Of the main risk factors, atherosclerosis, smoking, diabetes, total cholesterol and HDL-cholesterol were equivalent, while triglycerides were higher in the hypertensive subjects than in the controls (142.6 +/- 52.7 vs. 112.6 +/- 67.7 mg/dl; p = 0.0065). In these subjects' sera the immunoglobulins IgG, IgA and IgM, and the third and fourth complement components (C3 and C4) were measured. Of these variables, only C3 was higher in the hypertensive subjects than in the controls (124.3 +/- 29.3 vs. 107.8 +/- 18.4 mg/dl; p = 0.0183). Furthermore, C3 was significantly correlated with triglycerides (tau = 0.3613; p < 0.0001), but the association with hypertension was confirmed only for C3, and not for triglycerides, by multiple logistic regression (p = 0.0142). The increase in serum C3 suggests the possible implication of humoral immunity in the pathogenesis or progression of essential hypertension.

Blood Pressure↗

PubMed1992

[Increased serum levels of IgA and C4 in atherosclerosis: the absence of a correlation with the arteriographic picture].

We have previously shown that an increase in serum IgA and C4 is often detectable in presence of diffuse atherosclerotic disease. The present study was performed to verify such results in a different and larger sample of subjects, and to ascertain whether the above immunologic variables are correlated with the severity of atherosclerotic disease. Seventy-three atherosclerotic subjects with at least 1 significant (> 75%) stenosis in a major arterial branch were selected according to the reports of arterial panangiographies performed previously. Among them, 36 subjects (24 men and 12 women, mean age 63 +/- 7 years) were singled out, who matched by age and sex 36 control subjects (mean age 63 +/- 7 years). In all of these subjects the following serum immunologic and lipid variables were measured: IgG, IgA, IgM, IgE, C3, C4, total cholesterol, HDL-cholesterol and triglycerides. With respect to the controls, the 36 matched atherosclerotic subjects had higher levels of IgA (263.0 +/- 119.8 vs 334.3 +/- 130.5 mg/dl; p = 0.0126), C4 (25.7 +/- 5.8 vs 30.4 +/- 9.1 mg/dl; p = 0.0297) and triglycerides (153.1 +/- 77.3 vs 209.7 +/- 141.3; p = 0.0500). No correlation was found between the number of arterial stenoses (range 1-8, mean 2.9 +/- 1.5) and any of the immunologic or lipid parameters in all the 73 atherosclerotic subjects. Only the daily cigarette consumption was correlated with the disease extension (tau = 0.1984; p = 0.0392).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1990

[The heart and central nervous system. Benzodiazepines in cardiovascular psychosomatic medicine].

In certain clinical situations, a close correlation between CNS alterations and changes in the normal functioning of the cardiovascular apparatus has been well documented. Thus, it has been shown that a certain type of behavior, termed type A, is significantly associated with coronary disease and other cardiovascular disorders. Stress, too, by activating complex neurohormonal mechanisms can become an important factor in the pathogenesis of these disorders. Systematic management of these disorders has not yet been worked out but centrally acting drugs, and especially benzodiazepines, have been found useful in reducing the stress reaction and the consequent psychosomatic cardiovascular involvement. Some molecules of this class of drugs have been shown to possess marked affinity for the cardiac muscle and to act effectively in control and suppression of the cardiovascular disorders following upon the neuro-hormonal activation caused by stressful events.

Benzodiazepines↗

PubMed1990

[ACE inhibitors and heart failure].

ACE-inhibitors have been shown to have considerable therapeutic effectiveness in the treatment of heart failure and to be able to significantly prolong the survival of treated patients. The benefits of these drugs when used in the treatment of heart failure are due to their vasodilator action on both arterial and venous vessels. An even more relevant mechanism might be the modulation of some neuro-endocrine responses induced by heart failure, such as angiotensin-aldosterone production, which are sometimes excessive or harmful. The molecules presently available in Italy are four (captopril, enalapril, lisinopril, quinapril), endowed with considerably different pharmacological characteristics, but substantially similar as far as effectiveness and tolerability are concerned. Although general guidelines cannot be suggested on the basis of the pharmacological profile alone, the choice of the drug to be used in every single patient with heart failure should be made taking into account the adequacy of the pharmacological properties for the specific situation.

Angiotensin-Converting Enzyme Inhibitors↗