Francesco Paolo Mancini's research while affiliated with Università degli Studi del Sannio and other places

Publications (81)

Article
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Cardiovascular disease (CVD) is still the leading cause of death worldwide. Despite successful advances in both pharmacological and lifestyle strategies to fight well-established risk factors, the burden of CVD is still increasing. Therefore, it is necessary to further deepen our knowledge of the pathogenesis of the disease for developing novel the...
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Aims Pulmonary hypertension (IP) characterized by an average resting pulmonary pressure ≥20 mmHg can sustain various clinical conditions that differ in physiopathological, haemodynamic, and therefore therapeutic aspects. The goal of our work was to apply a machine learning algorithm that could accurately distinguish pre- and post-heart pulmonary hy...
Article
Fibrotic diseases are still a serious concern for public health, due to their high prevalence, complex etiology, and lack of successful treatments. Fibrosis consists of excessive accumulation of extracellular matrix components. As a result, the structure and function of tissues are impaired, thus potentially leading to organ failure and death in se...
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Cells with contractile functions are present in almost all metazoans, and so are the related processes of muscle homeostasis and regeneration. Regeneration itself is a complex process unevenly spread across metazoans that ranges from full-body regeneration to partial reconstruction of damaged organs or body tissues, including muscles. The cellular...
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This study sought to determine the possible detrimental effects of several low- or non-caloric sweeteners on endothelial progenitor cells (EPCs), inflammation and behavioural changes in mice. C57BL/6 male mice received low and high dose of natural and artificial sweeteners for 4 weeks. EPCs, physical and biochemical variables, inflammation and beha...
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Importance Although increasingly strong evidence suggests a role of maternal total cholesterol and low-density lipoprotein cholesterol (LDLC) levels during pregnancy as a risk factor for atherosclerotic disease in the offspring, the underlying mechanisms need to be clarified for future clinical applications. Objective To test whether epigenetic si...
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Cell therapy is a central issue of regenerative medicine and is raising a growing interest in the scientific community, but its full therapeutic potential in coronary heart disease (CHD) has not been reached yet. Several different methods, cell types, delivery routes, and supporting techniques have been attempted and improved to elicit cardiac rege...
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TheCDKN1Cgene encodes the p57Kip2protein which has been identified as the third member of the CIP/Kip family, also including p27Kip1and p21Cip1. In analogy with these proteins, p57Kip2is able to bind tightly and inhibit cyclin/cyclin-dependent kinase complexes and, in turn, modulate cell division cycle progression. For a long time, the main functio...
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Fighting diseases and controlling the signs of ageing are the major goals of biomedicine. Sirtuins, enzymes with mainly deacetylating activity, could be pivotal targets of novel preventive and therapeutic strategies to reach such aims. Scientific proofs are accumulating in experimental models, but, to a minor extent, also in humans, that the ancien...
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Background and aim: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impressive. However, there are always novel frontiers coming up and epigenetics is one of these. Sirtuins, are pivotal factors in the control of metabolic pathways according to nutr...
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p27Kip1 is a cell cycle regulator firstly identified as a cyclin-dependent kinase inhibitor. For a long time, its function has been associated to cell cycle progression inhibition at G1/S boundary in response to antiproliferative stimuli. The picture resulted complicated by the discovery that p27Kip1 is an intrinsically unstructured protein, with n...
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Type 1 diabetes (T1D) is an irreversible degenerative disease with severe complications such as heart disease, nephropathy, neuropathy, and retinopathy. Although exogenous insulin administration is a life-saving therapy, it does not cure the disease. This review addresses the epigenetic mechanisms responsible for the development of T1D and discusse...
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The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited a...
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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to...
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Muscle and connective tissues are structures that provide stability and movement to organisms belonging to the animal kingdom. Fascia and muscle tissues structurally and functionally integrate to form a musculofas-cial system with exceptional biomechanical properties, which allow animals to accomplish complex tasks. Mechanical overload through inte...
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Sirtuin 6 (SIRT6) is a member of the sirtuin family NAD⁺-dependent deacetylases with multiple roles in controlling organism homeostasis, lifespan, and diseases. Due to its complex and opposite functional roles, this sirtuin is considered a two-edged sword in health and disease. Indeed, SIRT6 improves longevity, similarly to the founding yeast membe...
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In cardiac fibrosis, following an injury or a stress, non-functional fibrotic tissue substitutes normal myocardium, thus leading to progressive heart failure. Activated fibroblasts are principal determinants of cardiac fibrosis by producing excessive fibrotic extracellular matrix and causing hypertrophy of cardiomyocytes. Epigenetic changes, such a...
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There is increasing evidence that diet plays a crucial role in age-related diseases and cancer. Oxidative stress is a conceivable link between diet and diseases, thus food antioxidants, counteracting the damage caused by oxidation, are potential tools for fight age-related diseases and cancer. Resveratrol (RSV), a polyphenolic antioxidant from grap...
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Cardiovascular disease is still the major cause of death worldwide despite the remarkable progress in its prevention and treatment. Endothelial progenitor cells have recently emerged as key players of vascular repair and regenerative medicine applied to cardiovascular disease. A large amount of effort has been put into discovering the factors that...
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Yin Yang 1 (YY1) is a member of polycomb protein family involved in epigenetic modifications and transcriptional controls. We have shown that YY1 acts as positive regulator of tumor growth and angiogenesis by interfering with the VEGFA network. Yet, the link between polycomb chromatin complex and hypoxia regulation of VEGFA is still poorly understo...
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Cell-based therapies, as potential approach to cure peripheral artery disease (PAD), have been clinically investigated after promising results in preclinical models. The so far published studies are very heterogeneous, as different cell sources, cell types, amounts of administered cells and delivering strategies have been used. Overall, cell therap...
Article
Cardiovascular disease (CVD), including cerebrovascular disease, is the leading cause of death worldwide. Although impressive advances in the knowledge of its pathological bases have been achieved, and effective therapies are constantly being developed, CVD still represents a major burden for public health. This is probably due to the multifactoria...
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UVB radiation causes about 90% of non-melanoma skin cancers by damaging DNA either directly or indirectly by increasing levels of reactive oxygen species (ROS). Skin, chronically exposed to both endogenous and environmental pro-oxidant agents, contains a well-organised system of chemical and enzymatic antioxidants. However, increased or prolonged f...
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Cardiovascular disease is the leading cause of morbidity and mortality in the world. In recent years, there has been an increasing interest both in basic and clinical research regarding the field of cell therapy for coronary heart disease (CHD). Several preclinical models of CHD have suggested that regenerative properties of stem and progenitor cel...
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Understanding the mechanisms inducing endothelial cell (EC) proliferation following tumor microenvironment stimuli may be important for the development of antiangiogenic therapies. Here, we show that cyclin-dependent kinase 2 and 5 (Cdk2, Cdk5) are important mediators of neoangiogenesis in in vitro and in vivo systems. Furthermore, we demonstrate t...
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In recent years the diagnosis of cardiovascular disease (CVD) has increased its potential, also thanks to mass spectrometry (MS) proteomics. Modern MS proteomics tools permit analyzing a variety of biological samples, ranging form single cells to tissues and body fluids, like plasma and urine. This approach enhances the search for informative bioma...
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Aim. Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors exert antiatherosclerotic effects in preclinical models and antioxidant effects in patients. However, whether ACE inhibitors have any clinically significant antiatherogenic effects remains still debated. Objectives. In mildly hypertensive patients, we evaluated the effect of the sulfhyd...
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Sensitized candidates for heart transplant usually end up on a long waiting list and have an increased risk of rejection, graft loss, and incidence of cardiac allograft vasculopathy. An increasing number of studies have demonstrated the negative effect of preformed and posttransplant antibodies on graft survival. Thus, in sensitized patients, the c...
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Innovative advances in understanding the pathogenesis of atherosclerosis have been achieved over the past 25 years. Although elevated levels of serum low-density lipoprotein cholesterol (LDL-C) are the major cause of onset of the disease, as established by a large number of superb epidemiological, clinical, and experimental studies, important novel...
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A great deal of evidences indicate that impaired fetal growth and in utero exposure to risk factors, especially maternal hypercholes-terolemia, may be relevant for human patho-physiological signs of atherosclerosis and subsequent development of cardiovascular disease (CVD) during different life stages. Despite the underlying mechanisms of fetal pro...
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Skin is exposed to both endogenous and environmental oxidant agents, leading to the harmful generation of reactive oxygen species. Particular interest has been pointed on plant antioxidants, such as resveratrol, because of their wide-ranging biological activity and clinical potential. Resveratrol exerts antioxidant, metabolism-regulating and pro-ap...
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Peripheral arterial disease (PAD) is a major health problem especially when associated to concomitant diabetes and hypercholesterolemia. Hyperglycemia with an overwhelming generation of oxygen radicals and formation of glycation end-products exacerbates oxidation-sensitive mechanisms activated by tissue ischemia. Administration of autologous bone m...
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Prostatic cancer may remain organ-confined indefinitely; in a number of patients, however it gives rise to clinical symptoms and death. The biological behaviour of this tumour mostly remains difficult to predict. A promising tool for diagnosis and prognosis of some human tumours is the chromatin assembly factor-1 (CAF-1), involved in the control of...
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In cultured prostate cancer cells cAMP blocks proliferation and induces neuroendocrine differentiation. Pyk2 expression inversely correlates with malignancy of prostate cancer. The aim of this study was to investigate the interaction between cAMP and Pyk2 in the prostate. EPN cells, a line derived from human normal prostate expressing Pyk2, and EPN...
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In cultured prostate cancer cells cAMP blocks proliferation and induces neuroendocrine differentiation. Pyk2 expression inversely correlates with malignancy of prostate cancer. The aim of this study was to investigate the interaction between cAMP and Pyk2 in the prostate. EPN cells, a line derived from human normal prostate expressing Pyk2, and EPN...
Article
Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors exert antiatherosclerotic effects in preclinical models and antioxidant effects in patients. However, whether ACE inhibitors have any clinically significant antiatherogenic effects remains still debated. In mildly hypertensive patients, we evaluated the effect of the sulfhydryl ACE inhibitor...
Article
To date, there is no report on the effect of antioxidants on endothelial progenitor cells (EPCs). This study shows that in vitro incubation of EPCs with vitamin C and E reverted the already well documented lowering effect of TNF-alpha on EPC number and increased p-p38 expression levels. In order to document major changes of gene expression levels a...
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Nitric oxide (NO) exerts a plethora of vascular beneficial effects. The NO-releasing beta-blocker nebivolol is a racemic mixture of D/L-enantiomers that displays negative inotropic as well as direct vasodilating activity. The in vivo antiatherogenic activity of therapeutic doses of the beta-blocker with antioxidant properties carvedilol (12.5mg/day...
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Chemokines, originally discovered as mediators of directional migration of immune cells to sites of inflammation and injury, have a function beyond their role in leukocyte chemotaxis. Indeed, they participate in organ development, angiogenesis, tumourigenesis and, more importantly, in the immune response. The chemokine family characterized by four...
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Circulating endothelial progenitor cells (EPCs) play a significant role in regeneration of damaged blood vessels. Levels and functional activities of EPCs are noticeable altered by risk factors for coronary heart disease (CHD) and compounds that can prevent or ameliorate EPC dysfunction are currently of special clinical interest. Here, we evaluate...
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The custom microenvironment 'vascular niche' is a potential therapeutic target for several pathophysiological conditions. Osteoblasts regulate the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor can increase the number of cells mobilized into the bloodstream. C57Bl/6 mice were randomly assigned treatment with...
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Proteomics has unraveled important questions in the biology of cardiovascular disease and holds even greater promise for the development of novel diagnostic and prognostic biomarkers. This approach may establish early detection strategies, and monitor responses to therapies. Technological advances (most notably blue native polyacrylamide gel electr...
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Gene-environment interaction is behind the pathogenesis of most widespread diseases, and nutrition is among the environmental factors with the highest impact on human health. The mechanisms involved in the interaction between nutritional factors and the genetic background of individuals are still unclear. The aim of this study was to investigate wh...
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Although prostate carcinoma is an aggressive cancer preferentially metastasizing to the bones, many prostate tumors remain localized and confined to the prostate indefinitely. Prediction of the behavior of anatomically localized and moderately differentiated prostate tumors remains difficult because of lack of prognostic markers. Cell motility is a...
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To analyse the association of the UCP2 gene, alone or in combination with the PPARgamma2 gene, with obesity. Cross-sectional, case-control study. From a working population of 4500 Italian Caucasian employees of the Italian telephone company participating in a firm-sponsored health screening programme, we selected all those with obesity [n = 122; bo...
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Background: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma gene has been associated in some, but not all, studies with lower body mass index (BMI) and improved insulin sensitivity; how an altered transcriptional activity of PPARgamma2 could influence insulin sensitivity is currently unclear. The free fatty...
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Uncoupling protein 3 (UCP3) is a member of the mitochondrial carrier superfamily, preferentially expressed in skeletal muscle. Its function is not fully understood and it is debated whether it uncouples oxidative phosphorylation as does UCP1 in brown adipose tissue. Recent evidences suggest a role for UCP3 in the flux of fatty acids in and out mito...
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Fibrates are hypolipidemic drugs that activate the peroxisome proliferator-activated receptors. Since fibrates may also increase energy expenditure, we investigated whether fenofibrate (FF) had this effect in diet-induced obese rats. A 2-month administration of a high-fat palatable diet to adult rats increased body weight by 25% and white adipose m...
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Homocysteine is involved in a complex and dynamic system of vascular injury and repair and may thus contribute to the development of diabetic microangiopathy. This still debated issue has important scientific and clinical implications, since hyperhomocysteinemia can be corrected nutritionally. 1) To evaluate the association between fasting plasma h...
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To explore the association of the Pro12Ala mutation in the peroxisome proliferator-activated receptor gamma2 with severe obesity and the features of the metabolic syndrome in a population-based sample of Caucasians. The study is based on a case-control design: 95 non-diabetic severely obese (body mass index, BMI > 35 kg/m2) cases and 280 normal wei...
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Over the last 30 years, a growing body of evidence has documented the role of hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the mechanisms through which elevated circulating levels of homocysteine (Hcy) cause vascular injury and promote thrombosis remain elusive. Most findings have been achieved in in vitro studies em...
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Peroxisome proliferator-activated receptor (PPAR)-gamma is a major regulator of adipogenesis and insulin sensitivity. The PPAR-gamma gene generates two isoforms through alternative splicing, PPAR-gamma1 and -gamma2, the latter having an additional stretch of 28 amino acids at its NH2-terminus in the ligand-independent activation domain. This extens...
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We investigated the influence of major cardiovascular risk factors (smoking, hypercholesterolemia, diabetes mellitus) on the association between angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism and echocardiographic left ventricular mass in 225 patients with sustained hypertension, assessed by ambulatory blood pressu...
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The angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism might be involved in the development of several cardiovascular diseases, but its role in humans remains controversial. To investigate the relation between the angiotensin converting enzyme gene polymorphism and extent of blood pressure elevation in arterial hypertension,...
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To the Editor: The association of the insertion/deletion (I/D) polymorphism of the ACE gene with ischemic vascular disease is disputed.1 Mistyping as DD of 4% to 5% of ID subjects may contribute to conflicting findings.2 3 The original method4 preferentially extends allele D. The addition of 5% DMSO, or the use of an allele-specific oligonucleoti...
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To determine whether oxidized LDL enhances atherogenesis by promoting monocyte recruitment into the vascular intima, we investigated whether LDL accumulation and oxidation precede intimal accumulation of monocytes in human fetal aortas (from spontaneous abortions and premature newborns who died within 12 h; fetal age 6.2+/-1.3 mo). For this purpose...
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In Western countries, acute myocardial infarction and stroke, are major causes of morbidity and mortality (1). An occlusive coronary thrombus on an ulcerated atherosclerotic plaque in the coronary arteries is the central event in more than 90% of patients with Q-wave myocardial infarction (2). The underlying abnormality in non-Q-wave infarctions is...
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Usual purification procedures of LDL and Lp(a) require numerous, extensive and prolonged sample handlings: this greatly increases the possibility of spontaneous oxidation. We have developed a method which, making use of two short-run ultracentrifugations in vertical rotors alternated by two rapid column-chromatography steps (SRUC), significantly sh...
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Familial hypercholesterolemia was the first genetic disorder recognized to cause myocardial infarction. Patients with homozygous familial hypercholesterolemia have rapidly progressive coronary atherosclerosis with angina pectoris, myocardial infarction, or sudden death at a young age. Selective apheresis on dextran sulfate cellulose columns reduces...
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Oxidation of low density lipoprotein (LDL) has been implicated in atherogenesis. An increased content of oleic acid in LDL and the substitution of monounsaturated for polyunsaturated fatty acids in the diet reduce LDL oxidation. With 1H-NMR analysis, all LDL modifications, including the production of copper-induced aldehyde products, can be evaluat...
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Abnormally high levels of some hemostatic variables are often associated with the occurrence of the major ischemic complications of atherosclerosis, myocardial infarction, and stroke. Intervention studies have shown that prolonged treatment with antiplatelet drugs significantly reduces the recurrence of coronary and cerebral ischemic episodes. The...
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To assess the relationship between the angiotensin converting enzyme (ACE) gene I/D polymorphism, blood pressure (BP) and family history of hypertension, 133 hypertensive subjects (mean age 50 +/- 9 years, 78 males, 55 females) were selected according to both casual supine BP > 140/90 mmHg and ambulatory BP > 134/88 mmHg. Drug treatment was discont...
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Among the factors involved in the pathogenesis of the atherothrombotic process, plasma homocysteine has been established as an independent risk factor. Many clinical studies have documented a higher prevalence of thromboembolic events in patients with increased plasma levels of homocysteine than in control populations. Many efforts have been made t...
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Moderate elevation of total plasma homocysteine (tHcy) has been reported as an independent risk factor for thrombotic vascular disease, a well-known multifactorial disorder. Possible genetic causes of elevated tHcy include defects of the sulfur-containing amino acids metabolism due to deficiencies of cystathionine Î-synthase, of 5,10-methylenetetra...
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Background: Plasminogen activator inhibitor-1 (PAI-1) is a determinant of vascular events. A guanine insertion/deletion polymorphism (4G/5G) modulates plasma levels of PAI-1. Moreover, the renin-angiotensin system has been reported to affect plasma PAI-1 levels in humans. Methods and Results: All the genotyping was carried out by polymerase chain r...
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Objectives. To evaluate the ability of lipoprotein(a), Lp(a), to discriminate subjects with a stroke history, as compared to that of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA). Design. Cross-sectional study. Subjects from a metabolic ward. Participants. A total of 210 subjects (108 men, 102 women, mean age 63....
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Subjects with homozygous homocystinuria due to cystathionine-β-synthase deficiency (CBSD) are at risk for arterial and venous thrombosis. In CBSD patients we have previously demonstrated an abnormally high biosynthesis of thromboxane A2 as reflected by the urinary excretion of its major metabolite 11-dehydro-thromboxane B2 (TXM), and its partial de...
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Moderate hyperhomocysteinemia is an independent risk factor for thrombotic vascular disease. A C677T substitution of the MTHFR gene has been reported as the leading cause of moderate hyperhomocysteinemia. We have evaluated the frequency of the C677T mutation of the MTHFR gene in 64 unrelated young thrombophilic patients. In 29 (16 men, 13 women, 37...
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Current knowledge indicates that high plasma levels of fibrinogen, a key protein in the hemostatic system, help predict the major ischemic complications of atherosclerosis, that is, stroke and myocardial infarction. Molecular variations at the fibrinogen genes loci have been shown to regulate fibrinogen concentrations in plasma. However, it is also...
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In this cross-sectional study we compared the abilities of lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) to discriminate between individuals with and without a history of stroke from among subjects in a metabolic ward. A total of 210 subjects (108 men and 102 women; mean age, 63.8 years; r...
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Current evidence indicates that plasma fibrinogen is synthesized by the Jiver; that genetic and environmental factors regulate plasma fibrinogen levels; that interleukin-6 (IL-6) affects the synthesis of plasma fibrinogen by mechanisms involving protein kinase C, and that during the acute-phase response, monocytes generate a variety of monokines in...
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We evaluated the genotypes of the angiotensin-converting enzyme (ACE) gene in 101 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. Genotypes were determined by polymerase chain reaction with oligonucleotide primers flank...

Citations

... Redox toxicity can occur as the result of exposure to oxidizing agents (ultraviolet and ionizing radiation, heavy metals, chemical toxins, etc.), from free radical production by normal physiological processes (mitochondrial oxidative phosphorylation, arachidonic acid metabolism, etc.), or from a deficit of antioxidant capacity of the cell [3,[5][6][7]. Redox imbalances have been implicated in a wide variety of chronic diseases, such as cancer, cardiovascular disease, kidney disease, fibrotic remodeling diseases, and a variety of neurological diseases [2,6,[8][9][10]. The cellular biological response to redox stress has been shown to depend upon the quantity, quality, duration, and total area of reactive species exposure [3,4,[11][12][13][14]. ...
... In this individual case, the ultrasound image of TLF morphology changed within 10 days after MFR treatment (Figure 4). This was surprising, as it would be expected that a change in tissue structure would take more time [51]. Although this case is not representative, it provides interesting food for thought regarding the mechanisms behind this improvement in morphology. ...
... For example, in the hydroid Podocoryna carnea, damage to the bell induces the dedifferentiation and migration of striated muscle cells that then fill the wound site and differentiate into functional muscle cells [6]. In Hydra, muscles are regenerated by stem cells [7,8]; in lancelets, the tail is regenerated through dedifferentiation and the oral cirri are regenerated by stem cells [8]. ...