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Biomedical subjects

A Auteri

Publications and source records attributed to A Auteri.

At least 19 recordsLinked to original sources
PubMed2007

Rett syndrome and plasma leptin levels.

OBJECTIVE: To describe in patients with Rett syndrome (classic and preserved-speech variant) plasma leptin levels and their relationship to BMI (body mass index) and age. STUDY DESIGN: Female patients (n = 48; age range 3-20 years) affected by classic Rett syndrome were enrolled into the study. Eleven female patients, age range 3 to 20 years, with preserved-speech variant Rett syndrome were included in the study. Controls were 24 healthy female subjects, age range 3 to 20 years. Blood samples (3 mL) were withdrawn from an antecubital vein in the morning; plasma leptin concentrations were detected by enzyme-linked immunosorbent assay method. RESULTS: Patients with classic Rett syndrome and preserved-speech variant had leptin values significantly higher than controls. Leptin concentrations did not significantly differ between patients with classic Rett and preserved-speech variant. Leptin values positively correlated with age and BMI. CONCLUSIONS: Because in all patients the increased leptin concentrations were not associated to obesity, we hypothesize that in patients with Rett syndrome leptin might participate to clinical manifestations other than weight balance.

Adolescent↗
PubMed2006

Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment.

BACKGROUND: Oxidized-LDL (ox-LDL) are involved in atherothrombosis by induction of endothelial dysfunction and thrombosis. The specific receptor lectin-like oxidized-LDL receptor-1 (LOX-1) is expressed in endothelial cells, monocytes and platelets. LOX-1 gene allelic variants (3'UTR/T) have been related with cardiovascular events and reduced anti-platelet activity induced by statins. OBJECTIVES: To detect whether LOX-1 polymorphisms could affect statins effectiveness in cardiovascular prevention. PATIENTS/METHODS: The present was a retrospective study performed in 751 white hypercholesterolemic subjects treated with increasing doses of atorvastatin (n=382, 247 male, 135 female) or simvastatin (n=369, 244 male, 125 female) up to 4 years, whose LDL target was 3.36 mmol/L according to the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATPIII). Single nucleotide polymorphism were evaluated by allelic discrimination assays (PCR), lipid profile by enzymatic-colorimetric methods and C-reactive protein (CRP) by a nephelometric technique. RESULTS: Twenty-three non-ST elevation (NSTEMI) and eleven ST-elevation myocardial infarction (STEMI) were encountered in the observational period without differences between treatments (p=0.175) and sex (p=0.139). Each symptomatic subject (10 reaching the appropriate LDL target and 24 with still undesirable LDL) had the 3'UTR/T allelic variant (adjusted O.R. 4.63, 95% C.I. 3.46-6.70, p<0.0001). Among patients not reaching LDL target the C allele resulted protective with respect to T carriers (p<0.00001). Also, similar changes of CRP resulted in different event rate between T and C carriers (p<0.001) in the whole cohort. CONCLUSIONS: In the studied population LOX-1 genetic variants influence cardiovascular risk reduction induced by statins also in patients not reaching the LDL target. The previously described LOX-1-related antithrombotic actions of both statins employed could have a specific role in what observed, suggesting a genetic influence in statins LDL-lowering partially related actions.

Aged↗
PubMed2006

Pro-inflammatory/anti-inflammatory cytokine imbalance in acute coronary syndromes.

The aim of this study was to evaluate the presence of an imbalance between proinflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We considered two groups of 26 and 28 patients with acute myocardial infarction (AMI) and unstable angina (UA) respectively, compared with a group of 30 patients with stable angina and 30 healthy volunteers. We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumour necrosis factor (TNF)alpha, which are well known to possess proinflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity. We also assessed the clinical characteristics of groups and, particularly, we evaluated the circulating levels of C-reactive protein (hs-CRP). We found a significant increase of IFNgamma and TNFalpha production (P<0.01) and a significant decrease of IL10 production (P<0.05) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes where found between AMI and UA patients and SA patients and controls. Circulating levels of hs-CRP were significantly increased (P<0.01) in patients with ACS compared with the other control groups. Our data showed an increased production of proinflammatory mediators in ACS that may be detectable both in circulating blood and in cell cultures where it is possible to evaluate in a better way the functional state of cells; this finding was associated with a reduced production of the antiinflammatory cytokine IL10. In conclusion, a relevant imbalance is present in ACS and this fact could contribute to plaque instability and clinical manifestations.

Acute Disease↗
PubMed2005

Variations of peripheral markers of serotoninergic system in selected vascular patients.

BACKGROUND AND AIM: Serotonin (5-HT), a decarboxylated derivative of tryptophan, is synthesized in the enterochromaffin cells and released into blood stream to be incorporated into platelets. At the site of endothelial lesions, platelets aggregate and secrete 5-HT that presents several vascular actions involved in thrombosis and atherogenesis. In fact, 5-HT may induce vasoconstriction in the presence of endothelial injury, aggregation of platelets, and mitogenesis of arterial smooth muscle cells and endothelial cells. It may also contribute to the vascular inflammation associated with atherogenesis by increasing the synthesis of Interleukin-6 in vascular smooth muscle cells. We evaluated serotonin levels in plasma and platelets of patients with unstable angina and ischemic stroke, to identify an association between serotonin and atherosclerosis of coronary and cerebral arteries. METHODS AND RESULTS: Twenty patients (14 men, 6 women, mean age 69 +/- 10 years) with unstable angina and 15 patients (7 men, 8 women, mean age 81 +/- 10 years) with ischemic stroke were included in the study. Twenty-four healthy subjects matched for age and sex constituted the control group. Blood samples were drawn in the morning to determine plasma and platelet concentrations of serotonin. In patients with unstable angina serotonin levels in platelets were significantly lower (p < 0.001) than those observed in controls, while serotonin concentrations in plasma did not significantly differ from those found in controls. In patients affected by stroke serotonin levels in plasma and in platelets did not significantly differ from those found in normal subjects. CONCLUSIONS: Our findings may contribute to the knowledge to different mechanisms involved in the pathogenesis of cardiac and cerebral ischemia.

Aged↗
PubMed2005

Cytokines in acute coronary syndromes.

The aim of this study was to show the presence of an imbalance between pro-inflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumor necrosis factor (TNF)alpha, which are well known to possess pro-inflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity, in two groups of 30 patients affected by acute myocardial infarction (AMI) and unstable angina (UA), compared with two equivalent groups of patients with stable angina (SA) and of healthy volunteers. We found a significant increase of IFNgamma and TNFalpha production (p<0.01) and a significant decrease of IL-10 production (p<0.01) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes were found between AMI and UA patients and SA patients and controls. We conclude that a relevant imbalance in cytokine release is present in ACS, markedly favoring pro-inflammatory effects.

Acute Disease↗
PubMed2005

Structural and functional abnormality of systemic microvessels in cardiac syndrome X.

BACKGROUND AND AIM: Microvascular damage of coronary bed has been considered the main pathogenetic factor of cardiac syndrome X (chest pain, exercise-induced ischemic ST-segment changes and angiographically normal coronary arteries). Previous studies have demonstrated that vascular abnormalities are not confined to the heart, suggesting a peripheral vascular dysfunction. On the hypothesis of a generalized microvascular disturbance in cardiac syndrome X, we performed a morphologic and functional study of systemic microcirculation in patients with syndrome X compared to normal subjects. METHODS AND RESULTS: Microvessels were evaluated with intravital videocapillaroscopy (VCP) executed in peripheral and conjunctival observation sites which explore micro and paramicrocirculation; biohumoral study included markers of inflammation and of endothelial function, coagulative-fibrinolytic system and lipid metabolism. Videocapillaroscopy showed several morphologic changes (present in high percent of patients with syndrome X and not in controls) and significant quantitative alterations (capillary density, granular flow score, alterations of vessel profile, length of capillary loop branches and of arteriole/venule diameter) which indicated a severe alteration of whole vessel structure and an important rearrangement of microvascular disposition. In a similar way, the humoral study showed some significant changes of endothelial (vWF, ICAM-1, E-sel, PAI-1), inflammatory (C-reactive protein (CRP), fibrinogen) and metabolic factors (HDL-chol) which are commonly associated with inflammatory response. CONCLUSIONS: We conclude that patients with cardiac syndrome X exhibited some structural and functional alterations of systemic microvasculature; the pattern is similar to that detected in systemic inflammatory diseases and suggests a vascular lesion of inflammatory type. The same changes could be operating also in coronary microvessels of patients with syndrome X.

Angina Pectoris↗
PubMed2005

Iloprost treatment reduces TNF-alpha production and TNF-RII expression in critical limb ischemia patients without affecting IL6.

Iloprost, a stable prostacyclin analogue, regulates expression of genes that are involved in inflammation and in cell growth and inhibits the in vitro production of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were stimulated with LPS for 24h. TNF-alpha production was significantly reduced by iloprost whereas IL6 production was not affected. Iloprost did not accelerate monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas TNF-RII mRNA expression was significantly reduced. Our data show that iloprost may have anti-inflammatory effects in addition to the well-known vasodilatatory and anti-aggregant ones.

Aged↗
PubMed2005

Extracorporeal photopheresis affects interleukin (IL)-10 and IL-12 production by monocytes in patients with chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photopheresis (ECP) has recently been introduced as an alternative treatment for cases of cGVHD refractory to conventional immunosuppressive treatment, but its mechanism of action is not yet clear. OBJECTIVES: To investigate in seven patients with cGVHD the effects of ECP on resistance of monocytes to apoptosis and on monocyte cytokine production. METHODS: We designed an in vitro model that could mimic the potential in vivo effect of reinfusion of peripheral blood mononuclear cells treated by ECP. The model was based on coculture of ECP-treated lymphocytes with untreated monocytes from the same patient. RESULTS: ECP did not accelerate spontaneous apoptosis of monocytes. However, ECP-treated monocytes produced increased amounts of interleukin (IL)-12. In contrast, IL-12 production by monocytes did not increase in cocultures, but IL-10 production was upregulated. CONCLUSIONS: These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through upregulation of IL-10, which is an immunosuppressive cytokine.

Adult↗
PubMed2005

Atorvastatin reduces platelet-oxidized-LDL receptor expression in hypercholesterolaemic patients.

BACKGROUND: Oxidized-LDL (ox-LDL) are proatherogenic and platelet-activating molecules. Atorvastatin reduces platelet activity before cholesterol-lowering action. CD36 and lectin-like oxidized-LDL receptor-1 (LOX-1) are specific ox-LDL receptors expressed also in platelets. This study was planned to address whether the possible rapid effect of atorvastatin on platelets could be related to modulation of ox-LDL receptors. MATERIALS AND METHODS: Forty-eight hypercholesterolaemic subjects requiring statin treatment (atorvastatin 20 mg day(-1)) after an ineffective diet regimen were evaluated for complete lipid-profile (chromogenic); P-selectin (P-sel), CD36 and LOX-1 expression (cytofluorimetric detection); circulating and platelet-associated ox-LDL (ox- and Pox-LDL, ELISA); and intracellular citrullin recovery (iCit, HPLC) at baseline and 3, 6 and 9 days after inclusion in the study. Moreover, we studied 48 normal controls matched for sex and age. RESULTS: Platelet activity expressed by P-sel (in resting and thrombin-activated cells), CD36 and LOX-1 were increased in hypercholesterolaemic subjects (all P < 0.01). Atorvastatin induced a reduction of CD36 at 6 days (P < 0.05); and P-sel in resting (P < 0.001) and activated cells (P < 0.001) and LOX-1 were reduced at 9 days (all P < 0.001) in association with decreased Pox-LDL (P < 0.001) and increased iCit (P < 0.01). All data were obtained before a significant reduction of LDL and ox-LDL was achieved (P = 0.109 and 0.113). DISCUSSION: Present data suggest that platelet deactivation by atorvastatin is related to CD36 and LOX-1 expression reduction before significant LDL changes. Moreover, the modulation of LOX-1 can be considered a self-relevant antiatherothrombotic action of atoravastin owing to the important role of this receptor in the ox-LDL-mediated vascular damage.

Adult↗
PubMed2005

Short-term and long-term effects of one-week treatment with intravenous iloprost in critical limb ischemia patients (Leriche-Fontaine stage III and IV).

AIM: Iloprost, usually administered through intravenous infusion for 6 hours per day for at least 21 days, is the main medical treatment for critical limb ischemia in patients unsuitable for surgical or endovascular approach. We evaluated the tolerance and the short-term and long-term effects of a single 1-week treatment in critical limb ischemia patients. METHODS: Twenty-nine patients in Leriche-Fontaine III and IV stage were treated with iloprost infusions for 16 hours per day for 7 days, achieving a maximal dose of 1.5 ng/kg/min. Tolerance and clinical assessment after treatment discontinuation and after 1 and 6 months were recorded; clinical evaluation (rest pain, trophic lesions), ankle/brachial pressure index (ABPI) and treadmill exercise test were performed before, immediately after treatment and after 1 and 6 months. RESULTS: No discontinuation of treatment occurred because of intolerance to iloprost. At the end of the treatment 69% of patients were responders, 55.2% at 1 month, 37.9% after 6 months. ABPI and treadmill maximum walking distance were improved by the treatment at every timepoint. After 6 months 10.3% mortality and 3.4% major amputation rates were recorded. There was a higher percentage of non-responders amongst women vs men, in diabetic patients vs non diabetic and in stage IV patients vs stage III. CONCLUSIONS: One-week treatment with iloprost is safe and effective in both Leriche-Fontaine stage III and IV patients. Clinical effects are persistent over time, often lasting up to the 6th month, similarly to the commonly used 28-day treatment, with clear implications in terms of patient's compliance and medical cost containment.

Aged↗
PubMed2004

Common variable immunodeficiency: a review.

Common variable immunodeficiency (CVID) is the commonest symptomatic primary antibody deficiency syndrome. The predominant manifestation is hypogammaglobulinemia. CVID is characterized by recurrent bacterial infections, especially of the upper and lower respiratory airways, and is also associated with an increased incidence of autoimmune and neoplastic disorders. Most patients are diagnosed as adults and delay in the recognition of the disease is common. Several T and B cell defects have been described, although the underlying cause is still unknown.

Common Variable Immunodeficiency↗
PubMed2004

Plasma brain natriuretic peptide levels in coronary heart disease with preserved systolic function.

We evaluated the circulating levels of brain natriuretic peptide (BNP) in stable angina, unstable angina, and myocardial infarction relating hormone levels to extension of coronary disease and number of vessels involved after angiographic examination. We studied 86 patients consecutively undergoing angiographic coronary examination and echocardiographic evaluation for coronary heart disease. These included 15 control subjects (group 0), 21 with stable angina (group I), 26 with unstable angina (group II), and 24 with non-Q myocardial infarction (group III). Patients with heart failure, a history of myocardial infarction, or recent myocardial damage with electrocardiographic S-T elevation were excluded. BNP levels in patients with unstable angina and myocardial infarction were significantly increased with respect to the group with stable angina (P<0.01). There were no differences between the groups with unstable angina and myocardial infarction. Analysis of peptide levels in relation to the number of involved vessels demonstrated a significant increase in patients with three-vessel disease compared with subjects with one or two vessels involved (P<0.03); among subjects with mono-vessel disease, patients with left descendent anterior stenosis had a more-marked BNP elevation than subjects with stenosis in other regions (P<0.01). Hence, BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction. BNP levels also seem to be related to the severity of coronary atherosclerosis and number of vessels involved. BNP could prove a novel marker for risk stratification, not only in heart failure but also in coronary heart disease.

Aged↗
PubMed2004

Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.

BACKGROUND: Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation. METHODS: Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment. RESULTS: PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05). CONCLUSIONS: The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.

Adult↗
PubMed2003

ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family.

Chronic graft-versus-host disease (cGVHD) is a severe and frequent complication of allogenic bone marrow transplantation which is often treated with extracorporeal photochemotherapy (ECP) with a positive clinical outcome in patients resistant to conventional protocols. The mechanism of action of ECP has not been fully elucidated, although several authors have reported that it is able to induce apoptosis. Using samples obtained from ten cGVHD patients, we sought to determine whether lymphocytes treated with ECP underwent apoptosis and, above all, the mechanisms involved. Lymphocytes at four stages were isolated: immediately before ECP, from the last buffy coat collected, after UV irradiation prior to reinfusion, and the day after ECP. When cultured for 48 h, lymphocytes treated with ECP underwent accelerated apoptosis (tested as annexin V binding cells and as intracellular histone-associated DNA fragments) in comparison with lymphocytes from the other samples. This enhanced programmed cell death could not be prevented by IL-2. Immediately after isolation, there was no difference in Bcl-2 or bax expression among the four different samples, or in Fas and FasL mRNA. However, when cultured, lymphocytes treated with ECP showed a rapid downregulation of Bcl-2, an upregulation of bax with an increased bax/Bcl-2 ratio, a decrease in bcl-2 mRNA and an increase in Fas. No changes were detectable in lymphocytes from the other samples. IL-2 and TNF-alpha production was not significantly different among lymphocytes from the four samples. In conclusion, in patients affected by cGVHD, ECP induced apoptosis of lymphocytes with the involvement of both the Fas/FasL system and the Bcl-2 protein family.

Adult↗
PubMed2003

T cell activation and enhanced apoptosis in non-ST elevation myocardial infarction.

Recent studies have shown that inflammation plays a major role in coronary plaque destabilization and in the induction of thrombosis in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte activation and apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with age-matched healthy controls. We considered T cell subpopulations, T cell surface HLA-DR and CD69 expression (evaluated by flow cytometry), lymphomonocyte spontaneous apoptosis (evaluated by ELISA), and IL2 production (evaluated by ELISA) in peripheral blood within 6 hours of onset of NSTEMI. We also investigated Fas expression on T cells (evaluated by flow cytometry) and FasL mRNA (evaluated by RT-PCR), as well as Fas functionality. In NSTEMI patients we found a significant increase of HLADR+ CD3+ and CD69+CD4+ cells. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and was associated with an increased expression of Fas, an increased susceptibility to Fas agonist (CH11), and a normal production of IL2 in cell cultures. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that peripheral lymphocytes are activated in NSTEMI and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.

Apoptosis↗