G M Puddu

Policlinico S.Orsola-Malpighi, Bolonia, Emilia-Romagna, Italy

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Publications (52)88.35 Total impact

  • A Muscari · G M Puddu · C Conte · R Falcone · B Kolce · M V Lega · M Zoli
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    ABSTRACT: Fever frequently occurs in stroke patients and worsens their prognosis. However, only few studies have assessed the determinants of fever in acute stroke, and no study has specifically addressed the possible prediction of the development of fever. This investigation included 536 patients with acute stroke and a body temperature <=37°C during the first 24 h of stay. Ninety-two of them (17.2%) subsequently developed fever (defined as a temperature >=37.5°C starting after 24 h). Among the clinical variables available during the first 24 h from admission, those predictive of the subsequent appearance of fever were searched for. One hundred further patients had a temperature >37°C during the first 24 h. In univariate analysis, many variables were predictive of the subsequent development of fever, but in multivariate analysis, only the following four predictors remained significant (odds ratio [95% confidence interval], P value): nasogastric tube (4.0 [2.2-7.4], <0.0001), atrial fibrillation (2.3 [1.4-3.8], 0.001), total anterior circulation syndrome (2.0 [1.2-3.5], 0.01), and urinary catheter (1.9 [1.1-3.3], 0.01). Among the 52 (9.7%) patients with three or four predictors, 31 (59.6%) subsequently developed fever. In addition, the factors independently associated with a temperature >37°C during the first 24 h were as follows: National Institutes of Health Stroke Scale (P < 0.0001), hemorrhagic stroke (P = 0.0008), atrial fibrillation (P = 0.002), and total parenteral nutrition (P = 0.03). In patients with acute stroke, four clinical variables were found to be independently associated with the risk of developing fever and, of them, nasogastric tube was the strongest and most significant one. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Acta Neurologica Scandinavica 02/2015; 132(3). DOI:10.1111/ane.12383 · 2.40 Impact Factor
  • A. Muscari · G. M. Puddu · C. Conte · R. Falcone · B. Kolce · M. V. Lega · M. Zoli
    International Journal of Stroke 10/2014; 9:91-91. · 3.83 Impact Factor
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    ABSTRACT: Background Small changes of bilirubin and liver enzymes are often detected during the acute phase of stroke, but their origin and significance are still poorly understood. Methods On days 0, 3, 7, and 14 after admission, 180 patients with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT, γGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count. On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day 3 cerebral infarct volume (IV) was calculated from CT scan slices. Results During the first week GOT, GPT, γGT (P < 0.001) and CRP (P = 0.03) increased with subsequent plateau, while significant decrements (P < 0.001) concerned unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase, direct bilirubin and common bile duct diameter remained stable. IV correlated with CRP, leukocytes, GOT, γGT (r > 0.3, P < 0.001 for all) and direct bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT remained independently associated with IV (P < =0.001). The correlation of IV with GOT increased progressively from admission to day 14. GOT independently correlated with GPT which, in turn, correlated with γGT. γGT was also highly correlated with leukocytes. Unconjugated bilirubin correlated with haemoglobin, which was inversely correlated with CRP. Conclusions The changes of bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which are both related to IV: 1) inflammation, with consequent increment of CRP, leukocytes and γGT, and decrease of haemoglobin and unconjugated bilirubin and 2) an unknown signal, independent from inflammation, leading to increasing GOT and GPT levels.
    BMC Neurology 06/2014; 14(1):122. DOI:10.1186/1471-2377-14-122 · 2.04 Impact Factor
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    ABSTRACT: Objectives: To find some specific determinants of lacunar strokes (LS), this study compared LS and non-LS patients using the size and location of cerebral lesions as discriminant between the two groups. Methods: The main cardiovascular risk factors and some echocardiographic parameters were assessed in 225 ischemic stroke patients aged 75·1±11·4 (SD) years, including 101 patients with symptoms and lesions of lacunar type (deep hypodensities with diameter ≤ 1·5 cm) and 124 patients with non-lacunar lesions. Results: LS patients tended to be younger and had a higher prevalence of smokers than non-LS patients. In a subgroup undergoing echocardiogram, those with LS had a higher left ventricular mass index (LVMI) than non-LS patients (141·6±44·9 vs. 115·1±31·8 g/m(2), P = 0·005). The prevalence of hypertension, diabetes, and carotid stenoses > 50% was similar in the two groups. In multivariable analysis the ever-smoker status (OR = 1·9, P = 0·02), atrial fibrillation (inverse association, OR = 0·5, P = 0·03), LVMI ≥ 130 g/m(2) (OR = 6·6, P = 0·001), and age ≤ 72 years (OR = 5·9, P = 0·003) remained independently associated with LS. Conclusions: The patients with lacunar cerebral lesions had a greater left ventricular mass than those with non-lacunar lesions, while blood pressure values did not differ. Lacunar lesions were also associated with smoking and a younger age.
    Neurological Research 07/2013; 35(10). DOI:10.1179/1743132813Y.0000000240 · 1.44 Impact Factor
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    ABSTRACT: Objectives: Several studies have sought factors predictive of early neurological deterioration during acute stroke; however, no study carried out a systematic search for factors capable of predicting early improvement. This investigation is aimed at identifying the variables associated with short-term neurological improvement in patients with ischemic stroke not undergoing thrombolysis. Methods: Two-hundred and fifty-two patients with ischemic stroke were retrospectively examined (mean age: 76.7 ± 10.6 years, 120 males, median delay of admission 8 hours). Stroke severity was assessed both on admission and at discharge (median stay: 4 days) by the National Institutes of Health Stroke Scale (NIHSS). Improvement was defined as a difference between initial and final assessment (ΔNIHSS) ≥ the median value (2 points). Thus, 127 patients improved (mean change: +3.8 points) and 125 did not (mean change: -1.4 points). Results: During the first 48 hours of hospitalization, 263 clinical, laboratory, instrumental, and therapeutic variables were collected. These were preliminarily compared between two subgroups of patients, improved and non-improved, which were matched for initial NIHSS score, and 17 possible predictors of improvement were found. The subsequent multivariable analysis led to the identification of four factors independently associated with improvement (odds ratio, 95% confidence interval): total anterior circulation syndrome (TACS) (0.20, 0.10-0.39, P<0.0001), aphasia (3.58, 1.89-6.77, P = 0.0001), average systolic blood pressure (0.98 per mmHg, 0.96-0.99, P = 0.002), and age (0.97 per year, 0.94-0.99, P = 0.02). Conclusions: The ischemic strokes that are not TACS, with aphasia, with normal/low blood pressure, or occurring in younger subjects, may have a significant tendency to short-term improvement.
    Neurological Research 02/2013; 35(6). DOI:10.1179/1743132813Y.0000000181 · 1.44 Impact Factor
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    ABSTRACT: Celiac disease (CD) is frequently associated with neurological disorders, but very few reports concern the association with ischemic stroke. A 26-year-old woman affected by CD with secondary amenorrhea, carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia, was affected by two occipital ischemic strokes within a period of 5 mo. At the time of the second stroke, while she was being treated with folic acid, acetylsalicylic acid and a gluten-free diet, she had left hemianopsia, left hemiparesthesias, and gait imbalance. Brain magnetic resonance imaging showed a subacute right occipital ischemic lesion, which was extended to the dorsal region of the right thalamus and the ipsilateral thalamo-capsular junction. Antitransglutaminase and deamidated gliadin peptide antibodies were no longer present, while antinuclear antibodies, antineuronal antibodies and immune circulating complexes were only slightly elevated. Since the patient was taking folic acid, her homocysteine ​​levels were almost normal and apparently not sufficient alone to explain the clinical event. A conventional cerebral angiography showed no signs of vasculitis. Finally, rare causes of occipital stroke in young patients, such as Fabry's disease and mitochondrial myopathy, encephalomyopathy, lactic acidosis and stroke-like symptoms, were also excluded by appropriate tests. Thus, the most probable cause for the recurrent strokes in this young woman remained CD, although the mechanisms involved are still unknown. The two main hypotheses concern malabsorption (with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immune-mediated mechanisms. CD should be kept in mind in the differential diagnosis of ischemic stroke in young patients.
    World Journal of Gastroenterology 07/2012; 18(26):3472-6. DOI:10.3748/wjg.v18.i26.3472 · 2.37 Impact Factor
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    ABSTRACT: Uric acid is the end product of purine metabolism. Its immediate precursor, xanthine, is converted to uric acid by an enzymatic reaction involving xanthine oxidoreductase. Uric acid has been formerly considered a major antioxidant in human plasma with possible beneficial anti-atherosclerotic effects. In contrast, studies in the past two decades have reported associations between elevated serum uric acid levels and cardiovascular events, suggesting a potential role for uric acid as a risk factor for atherosclerosis and related diseases. In this paper, the molecular pattern of uric acid formation, its possible deleterious effects, as well as the involvement of xanthine oxidoreductase in reactive oxygen species generation are critically discussed. Reactive oxygen species contribute to vascular oxidative stress and endothelial dysfunction, which are associated with the risk of atherosclerosis. Recent studies have renewed attention to the xanthine oxidoreductase system, since xanthine oxidoreductase inhibitors, such as allopurinol and oxypurinol, would be capable of preventing atherosclerosis progression by reducing endothelial dysfunction. Also, beneficial effects could be obtained in patients with congestive heart failure. The simultaneous reduction in uric acid levels might contribute to these effects, or be a mere epiphenomenon of the drug action. The molecular mechanisms involved are discussed.
    Journal of Cardiology 03/2012; 59(3):235-42. DOI:10.1016/j.jjcc.2012.01.013 · 2.78 Impact Factor
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    A Muscari · G M Puddu · N Santoro · M Zoli
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    ABSTRACT: According to most existing models, a computer is usually needed for predicting stroke outcome. Our purpose was to construct a simple and reliable prognostic scale not requiring the use of a calculating machine. The scale [the Bologna Outcome Algorithm for Stroke (BOAS)] was obtained in 221 patients with ischemic stroke not undergoing thrombolysis and was then validated in a test group of 100 different patients. Outcome was assessed at 9 months as the number of dependent or dead patients (modified Rankin scale - mRS > 2). By a preliminary systematic univariate analysis, 25 of 415 baseline variables were found to be associated with a mRS > 2 independently of stroke severity and age. Subsequent multivariable analyses led to a final model based on five dichotomous risk factors (RF): National Institutes of Health Stroke Scale score ≥10, age ≥78, need of urinary catheter, oxygen administration, and persistence of upper limb paralysis at discharge from stroke unit. The patients with two or more RF (53%) had a mRS > 2 in 91% of cases and were dead in 42% of cases. With 0-1 RF, the two percentages were 24% and 2%, respectively (overall accuracy of prediction 83.9%, area under ROC curve [AUC] 0.891). In the test group, the accuracy was 79.0% and the AUC was 0.839. The need of urinary catheter, oxygen administration, and persistence of upper limb paralysis, together with stroke severity and advanced age, allow a simple and accurate prediction of dependency or death after ischemic stroke.
    Acta Neurologica Scandinavica 11/2011; 124(5):334-42. DOI:10.1111/j.1600-0404.2010.01479.x · 2.40 Impact Factor
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    ABSTRACT: Statins have antioxidant, anti-inflammatory, anticoagulant, and profibrinolytic properties that might play a useful role in the acute phase of ischemic stroke. This pilot study assessed the possible neuroprotective action of high-dose atorvastatin administration during the first week after an ischemic stroke, to obtain data for planning a wider multicenter study. Sixty-two patients with ischemic stroke, aged 75.3 (SD, ±11.9) years (68% women), were randomized into a placebo (n = 31) and an atorvastatin 80 mg/d (n = 31) group. The double-blind treatment lasted 7 days. The primary end point was a decrease of National Institutes of Health Stroke Scale score of 4 points or higher after 7 days. Infarct volume measured on computed tomographic scan after 3 days and a modified Rankin Scale of less than 2 at 3 months were secondary end points. There was no difference in the primary end point between the 2 groups (odds ratio, atorvastatin vs placebo, 0.74; 95% confidence interval, 0.26-2.17). Infarct volume also was similar in the 2 groups. Instead, there were more patients with modified Rankin Scale of less than 2 at 3 months in the atorvastatin than in the placebo group (adjusted odds ratio, 6.7; 95% confidence interval, 1.0-45.0; P = 0.05). This prevalence concerned only the subgroup with mild strokes (National Institutes of Health Stroke Scale, ≤10; 53.8% vs 15.4%, respectively; P = 0.04). Atorvastatin was well tolerated. This pilot study was unable to show any short-term benefit of atorvastatin during the acute phase of ischemic stroke. However, it suggested a possible favorable functional effect at 3 months in the least severe strokes, which could be the primary end point for a future multicenter trial.
    Clinical neuropharmacology 06/2011; 34(4):141-7. DOI:10.1097/WNF.0b013e3182206c2f · 2.01 Impact Factor
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    ABSTRACT: Accumulating evidence suggests that dendritic cells (DCs) play a crucial role in the generation and progression of atherosclerosis (ATS), a lipid-related immuno-inflammatory disease. DCs have the ability to process and present antigens (mainly oxidized low-density lipoproteins, heat shock proteins and fragments of necrotic or apoptotic cells) to naive T cells, and the activation of T cells is a key step for the progression of atherosclerotic disease. The existence of some distinct DC subtypes has now become evident. The main categories of DC subsets are the 'conventional or myeloid' and the 'plasmacytoid', which differ in toll-like receptor type and site of expression, pathogens and antigens recognized, and effector cytokines and functions. Studies on the potential impact of DCs in the pathogenesis of ATS may lead to novel therapies to regulate the immunoreactions occurring in atherogenesis. In particular, diltiazem, peroxisome proliferator activated receptor agonists and statins have been shown to protect endothelial cell function by inhibiting DCs, a mechanism that may play a significant role in the prevention of ATS.
    Molecular Medicine Reports 07/2010; 3(4):551-4. DOI:10.3892/mmr_00000295 · 1.55 Impact Factor
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    ABSTRACT: Microparticles (MPs) are small vesicles, ranging in size from 0.1 microm to 2 microm, originating from plasma membranes of endothelial cells, platelets, leukocytes and erythrocytes. MPs can transfer antigens and receptors to cell types that are different from their cell of origin. Circulating MPs provide a procoagulant aminophospholipid surface for the assembly of the specific enzymes of coagulation. Both tissue factor and phosphatidylserine are exposed on MP outer membranes. In addition, MPs can play a significant role in vascular function and inflammation by modulating nitric oxide and prostacyclin production in endothelial cells, and stimulating cytokine release and tissue factor induction in endothelial cells, as well as monocyte chemotaxis and adherence to the endothelium. Finally, increased levels of MPs have been found in the presence of acute coronary syndromes, ischemic stroke, diabetes, systemic and pulmonary hypertension, and hypertriglyceridemia. From a practical point of view, MPs could be considered to be important markers of cardiovascular risk, as well as surrogate end points for assessing the efficacy of new drugs and therapies.
    The Canadian journal of cardiology 04/2010; 26(4):140-5. DOI:10.1016/S0828-282X(10)70371-8 · 3.94 Impact Factor
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    ABSTRACT: An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.
    Journal of Biomedical Science 12/2009; 16(1):112. DOI:10.1186/1423-0127-16-112 · 2.76 Impact Factor
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    ABSTRACT: Platelet functions are multiple, complex and not limited to haemostasis. In fact, platelets play a relevant role in vascular inflammation and atherosclerosis (ATS). In the presence of vascular lesions or inflammation, endothelial denudation or activation triggers mechanisms that render the circulating platelets adhesive for the vascular wall. Endothelial lesions expose subendothelial matrix components, such as collagen, von Willebrand factor, fibronectin and other adhesive proteins. Platelet adhesion depends on the interaction between these components and platelet receptors (mainly glycoprotein (GP) VI and GPlb-IX-V). Adhesion triggers the platelet release of inflammatory and mitogenic substances that alter the thromboresistant endothelial surface, enhance the chemoattraction of leukocytes, stimulate smooth muscle cell proliferation and contribute to matrix degradation. Finally, GPIIb-IIIa receptors are activated, leading to firm platelet aggregation and thrombus formation. Platelets participate in the formation of mural thrombi in the late stages of atherosclerotic disease, but also adhere to endothelial cells during the earlier stages of atherosclerotic plaque development. Moreover, platelets exert important functions in modulating inflammatory and immune processes. An improved comprehension of the complex platelet pathophysiology could suggest new therapeutic strategies to reduce the impact of atherosclerotic disease.
    Acta cardiologica 05/2009; 64(2):157-65. DOI:10.2143/AC.64.2.2035338 · 0.65 Impact Factor
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    ABSTRACT: Mean platelet volume (MPV) has been associated with the prognosis in stroke patients. However, its spontaneous variability during the acute phase of the disease is unknown. Materials and Methods - One hundred and thirty-seven patients with ischemic stroke, aged 75.4+/-11.0 (SD) years, were classified according to several criteria: National Institutes of Health Stroke Scale (NIHSS) score, maximum lesion diameter on CT scan, Oxfordshire Community Stroke Projects (OCSP) and Trial of ORG 10172 in Acute Stroke Treatment (TOAST) categories. Platelet parameters were determined 1.2 days after the onset of symptoms, and after 3.0 further days. The initial MPV was higher in non-lacunar than lacunar strokes (8.30+/-1.10 vs. 7.95+/-0.79 fl, P=0.04), and correlated with the sampling delay with respect to the onset of symptoms, especially in the strokes with lesions >=4 cm (r=0.39, P=0.009), NIHSS >=11 (r=0.35, P=0.02) and of cardioembolic origin (r=0.35, P=0.01). Subsequently a late MPV increment was observed in the remaining categories: from 8.20 to 8.38 fl (P=0.02) in the strokes with lesions <4 cm, from 8.11 to 8.31 fl (P=0.01) in the presence of an NIHSS<11 and from 8.20 to 8.61 fl (P=0.03) when the occlusion of a large artery was involved. Platelet volume is not stable during the acute phase in non-lacunar ischemic strokes, as it increases early in the most severe forms, and later in the remaining subtypes. The release of large and more reactive platelets may contribute to the thrombophilic state associated with ischemic events.
    Thrombosis Research 06/2008; 123(4):587-91. DOI:10.1016/j.thromres.2008.03.025 · 2.45 Impact Factor
  • Paolo Puddu · Giovanni Maria Puddu · Eleonora Cravero · Marzia Rosati · Antonio Muscari
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    ABSTRACT: In both animal models and humans, increased blood pressure has been associated with oxidative stress in the vasculature, i.e. an excessive endothelial production of reactive oxygen species (ROS), which may be both a cause and an effect of hypertension. In addition to NADPH oxidase, the best characterized source of ROS, several other enzymes may contribute to ROS generation, including nitric oxide synthase, lipoxygenases, cyclo-oxygenases, xanthine oxidase and cytochrome P450 enzymes. It has been suggested that also mitochondria could be considered a major source of ROS: in situations of metabolic perturbation, increased mitochondrial ROS generation might trigger endothelial dysfunction, possibly contributing to the development of hypertension. However, the use of antioxidants in the clinical setting induced only limited effects on human hypertension or cardiovascular endpoints. More clinical studies are needed to fully elucidate this so called "oxidative paradox" of hypertension.
    Blood Pressure 02/2008; 17(2):70-7. DOI:10.1080/08037050802029954 · 1.81 Impact Factor
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    ABSTRACT: Hypertension is a condition associated with oxidative stress, endothelial dysfunction, and increased vascular resistance, representing probably both a cause and a consequence of elevated levels of reactive oxygen (ROS) and nitrogen (RNS) species. Mitochondria are important sites of ROS production, and a mitochondrial dysfunction, preceding endothelial dysfunction, might favor the development of hypertension. ROS production may also be induced by RNS, which inhibit the respiratory chain and may be generated through the action of a mitochondrial NO synthase. Mitochondrial uncoupling proteins are involved in both experimental and human hypertension. Finally, an excessive production of ROS may damage mitochondrial DNA, with resultant impairment in the synthesis of some components of the respiratory chain and further ROS production, a vicious cycle that may be implicated in hypertensive states.
    Clinical and Experimental Hypertension 11/2007; 29(7):427-34. DOI:10.1080/10641960701613852 · 1.23 Impact Factor
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    ABSTRACT: During the last few years the studies on the genetic basis of essential hypertension (EH) have been numerous, allowing however only a partial understanding of the underlying molecular mechanisms. The most used techniques were the candidate gene approach, genome-wide scanning, the intermediate phenotype approach and comparative-genomics in animal models. The renin-angiotensin-aldosterone system may play a prominent role in the genesis of hypertension, and polymorphisms of the genes coding for angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 and 2 receptors, and aldosterone synthase have been widely studied. Other mechanisms may involve the KLK 1 gene of tissue kallikrein, gene variants of endothelial nitric oxide synthase and polymorphisms of the endothelin-1 gene. Finally, a number of studies have highlighted the potential contribution of polymorphisms of genes coding for inflammatory cytokines, adrenergic receptors and intracellular G proteins, which can activate Na+/K+ exchangers. Further important information might derive from proteomic analysis and the study of mitochondrial genome. Overall, results have often been discordant, sometimes suggesting a different expression of the same gene variants in different populations. EH is a highly polygenic condition, caused by the combination of small changes in the expression of many genes, in conjunction with a variable collection of environmental factors.
    Acta cardiologica 07/2007; 62(3):281-93. DOI:10.2143/AC.62.3.2020818 · 0.65 Impact Factor
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    ABSTRACT: Many experimental studies have obtained a prolonged control of blood pressure through gene treatment. This consists in the administration of genes coding for vasodilator proteins (the 'sense' approach), or of nucleotide sequences that are complementary to the mRNA of vasoconstrictor proteins, which are consequently synthesized in smaller amounts (the 'antisense' approach). Examples of the sense approach include the genes encoding endothelial nitric oxide synthase and kallikrein. Examples of the second type of approach are the antisense oligodeoxynucleotides to angiotensin-converting enzyme and endothelin-1. Also, RNA molecules, such as ribozymes and small interfering RNAs, are capable to inhibit RNA function. Whole sense genes are usually administered through viral vectors, while antisense oligonucleotides may be administered with plasmids or liposomes. Both viral and non-viral vectors have advantages and disadvantages. Despite the still persisting limitations, the possibility exists that in the future some forms of genetic treatment will be extended to the clinical setting, allowing a prolonged control of essential hypertension and its end-organ sequelae.
    Cardiology 02/2007; 108(1):40-7. DOI:10.1159/000095688 · 2.18 Impact Factor
  • Giovanni Maria Puddu · Eleonora Cravero · Giorgia Arnone · Antonio Muscari · Paolo Puddu
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    ABSTRACT: The development of atherosclerotic disease results from the interaction between environment and genetic make up. A key factor in atherogenesis is the oxidative modification of lipids, which is involved in the recruitment of mononuclear leukocytes to the arterial intima--a process regulated by several groups of adhesion molecules and cytokines. Activated leukocytes, as well as endothelial mitochondria, can produce reactive oxygen species (ROS) that are associated with endothelial dysfunction, a cause of reduced nitric oxide (NO) bioactivity and further ROS production. Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) are nuclear receptors significantly involved in the control of lipid metabolism, inflammation and insulin sensitivity. Also, an emerging role has been suggested for G protein coupled receptors and for the small Ras and Rho GTPases in the regulation of the expression of endothelial NO synthase (eNOS) and of tissue factor, which are involved in thrombus formation and modulation of vascular tone. Further, the interactions among eNOS, cholesterol, oxidated LDL and caveola membranes are probably involved in some molecular changes observed in vascular diseases. Despite the relevance of oxidative processes in atherogenesis, anti-oxidants have failed to significantly improve atherosclerosis (ATS) prevention, while statins have proved to be the most successful drugs.
    Journal of Biomedical Science 01/2006; 12(6):839-53. DOI:10.1007/s11373-005-9024-z · 2.76 Impact Factor
  • P Puddu · E Cravero · G M Puddu · A Muscari
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    ABSTRACT: Atherosclerosis (ATS) is a multifactorial disease caused by the interaction of established or emerging risk factors with multiple predisposing genes that regulate ATS-related processes. This review will discuss the current knowledge concerning the potential role of the genetic variations that could promote and/or accelerate ATS, in both animal models and humans. Allelic polymorphisms or variations of distinct genes that enhance the risk of ATS frequently occur in the general population, but only adequate gene-environment interactions will lead to the disease. The main genes so far studied are involved in the regulation of processes such as endothelial function, antioxidant potential, coagulation, inflammatory response, and lipid, protein and carbohydrate metabolism. The detection of candidate genes associated with ATS could allow, in the near future, earlier interventions in genetically susceptible individuals. Further, large-scale population studies are needed to obtain more information on the specific gene-environment and drug-gene interactions capable of influencing ATS progression.
    International Journal of Clinical Practice 05/2005; 59(4):462-72. DOI:10.1111/j.1368-5031.2005.00439.x · 2.57 Impact Factor

Publication Stats

913 Citations
88.35 Total Impact Points


  • 2005–2015
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy
  • 1990–2012
    • University of Bologna
      • Department of Medical and Surgical Sciences DIMEC
      Bolonia, Emilia-Romagna, Italy
  • 1996–1997
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
  • 1991–1993
    • Università Politecnica delle Marche
      Ancona, The Marches, Italy