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Biomedical subjects

Aldo Dobrina

Publications and source records attributed to Aldo Dobrina.

At least 19 recordsLinked to original sources
PubMed2005

Interleukin-1 receptor antagonist levels correlate with extent of myocardial loss in patients with acute myocardial infarction.

BACKGROUND: Interleukin-1 receptor antagonist (IL-1Ra) levels are elevated early in patients with acute myocardial infarction (MI) and often precede release of markers of necrosis; however, IL-1Ra levels did not correlate previously with infarct size and prognosis in such patients. HYPOTHESIS: The goal of our study was to evaluate prospectively the correlation between IL-1Ra levels upon emergency department (ED) presentation and the extent of myocardial necrosis and prognosis in patients with ST-segment elevation MI. METHODS: Levels of IL-1Ra were measured upon ED presentation in 44 consecutive patients (40 men, aged 55 +/- 10 years). Peak values of creatine kinase (CK) and CK-MB were determined during hospitalization, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography before discharge. All patients were followed prospectively and underwent clinical and echocardiographic assessment at 42 +/- 3 months after the infarction. RESULTS: Levels of IL-1Ra upon ED presentation correlated directly with CK (p = 0.002) and CK-MB (p = 0.01) peak levels and correlated inversely with LVEF before discharge (p = 0.009). Patients with in-hospital adverse events had significantly higher IL-1Ra levels upon ED admission (n = 10,2620 +/- 4706 pg/ml) than those without events (n = 34,598 +/- 457 pg/ml) (p = 0.015). CONCLUSIONS: In patients with MI, levels of IL-1Ra upon ED presentation correlated significantly with the extent of myocardial necrosis, as measured by cardiac enzymes peak and reduction of LVEF, and are predictive of in-hospital events. Results of this study may influence early therapeutic approach in patients with acute MI.

Adult↗
PubMed2005

Endothelial dysfunction and activation as an expression of disease: role of prostacyclin analogs.

The endothelium is now considered a real endocrine-paracrine organ, important not only as a structural barrier between the circulation and surrounding tissue, but also because it plays an essential role for local hemodynamics, releasing substances that modulate the vascular calibre and blood cell activation. Here, after a brief but detailed analysis of the importance of the endothelium in vascular homeostasis, in the control of coagulation and in the relations with the different blood cells, we will explain the concept of endothelial dysfunction (altered NO release) and activation (amplified adhesion molecule expression) in inflammatory, connective tissue and post-trasplantation diseases. Furthermore, this review will focus on the activity of prostacyclin and synthetic analogs, especially their ability to interact with the vasodilatation system and their role in modulating cell interaction by surface adhesion molecule expression, cytokines and growth factors release as well as gene transcription factors. Finally, we will consider the therapeutic role of prostacyclin analogs in the prevention and treatment of connective tissue diseases.

Connective Tissue Diseases↗
PubMed2005

Iloprost: an adjunctive approach to chronic viral hepatitis treatment.

Chronic viral liver disease may evolve to cirrhosis. The medical treatment to slow down this passage is based on anti-viral and anti-fibrotic properties of interferon. Recently, we evidenced significant increase of portal vein flow velocity and volume after a prostacyclin analog (iloprost) infusion in subjects without and with chronic viral hepatitis. On the basis of these results and considering both the pathophysiology of viral liver disease and the mechanism of action of iloprost in portal microcirculation, we hypothesize that it may be of some efficacy in chronic liver disease ameliorating the portal hemodynamics and producing an anti-oxidant liver effect.

Animals↗
PubMed2005

Genotypes and haplotypes in the IL-1 gene cluster: analysis of two genetically and diagnostically distinct groups of Alzheimer patients.

Increased risk of Alzheimer's disease (AD) has been associated with polymorphisms in the IL-1 gene cluster, and in particular with the IL-1alpha-889 T/T genotype. However, this association is still unclear, and needs further investigation. In order to clarify the role of these polymorphisms in the complex pathogenesis of AD we examined genotype and haplotype frequencies of the two C-to-T SNPs at position -889 and -551 in the IL-1alpha and IL-1beta genes, respectively, and of the 86 bp VNTR intron-2 polymorphisms in the IL-1Ra gene. The analysis was performed in two genetically and diagnostically distinct groups of sporadic AD from Italy and the USA. In the Italian group a significant association between the IL-1alpha-889 T/T genotype and AD (OR=3.022, 95% CI: 1.001-9.119) was found, whereas no difference was found in the group from the USA. Results were also compared with previously published studies that analyzed the same IL-1 polymorphisms in AD. In both groups, the analysis of the estimated haplotypes shows that AD patients and controls who carry the IL-1beta-511 C allele, were also more frequently carriers of the IL-1Ra 1 allele (haplotypes -C-1). The total frequency of the two -C-1 haplotypes (C-C-1 plus T-C-1) was about one half of the total frequency of the eight estimated haplotypes. This was confirmed by significant linkage disequilibrium between these two loci in both the Italian and USA groups. In the Italian group a weak association of the T-C-2 haplotype with the disease (OR=1.648, 95% CI: 1.519-1.788) was also found, whereas in the USA group no difference was found. Although ours and other published data on different samples of Caucasian and non-Caucasian AD show a great heterogeneity in the frequencies of the IL-1alpha-889, the IL-1beta-511 and the IL-1Ra VNTR gene polymorphisms, we confirm the role of the IL-1alpha-889 T/T genotype as a risk factor for sporadic AD, and show the presence of an allelic association between IL-1beta C and IL-1Ra 1 alleles in both the Italian and the USA groups, confirmed by the presence of significant levels of linkage disequilibrium between these two loci.

Aged↗
PubMed2004

Assessment of systemic inflammation and infective pathogen burden in patients with cardiac syndrome X.

Inflammation plays a key role in coronary artery disease (CAD), but whether it is involved in the pathogenesis of syndrome X (SX) is not known. Thus, we assessed the presence of systemic inflammation in patients with SX and its possible relation to infections from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus. We studied 55 patients with SX (57 +/- 8 years old; 27 women), 49 with stable angina and obstructive CAD (56 +/- 8 years old; 24 women), and 60 healthy controls (57 +/- 11 years old; 24 women). Plasma levels of high-sensitivity C-reactive protein and interleukin-1 receptor antagonist were measured in all patients. Infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus was assessed in 43 patients with SX, 40 patients with CAD, and in 39 controls. Patients with SX had lower serum levels of C-reactive protein than did patients with CAD (4.06 +/- 6.8 vs 5.99 +/- 7.8 mg/L, p = 0.013) but higher levels of C-reactive protein than did controls (1.75 +/- 1.98 mg/L; p = 0.008). Plasma levels of interleukin-1 receptor antagonist were higher in patients with CAD (570 +/- 738 pg/ml) and patients with SX (494 +/- 677 pg/ml) than in controls (254 +/- 174, pg/ml; p = 0.0003 vs CAD and p = 0.013 vs SX) but did not differ significantly between patients with CAD or SX (p = 0.20). There were no differences across groups in the prevalence of infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus and in the prevalence of 1, 2, 3, and 4 infections (p = 0.99). Among patients with SX, no correlation was found between markers of inflammation and indexes of disease activity (angina episodes, exercise test results). Our data show evidence of increased low-grade systemic inflammation in patients with cardiac SX, which was unrelated to an increased infectious pathogen burden.

C-Reactive Protein↗
PubMed2004

Widespread myocardial inflammation and infarct-related artery patency.

BACKGROUND: Diffuse coronary vascular inflammation is associated with acute coronary syndromes. However, it is unknown whether inflammation also occurs within the myocardium. Therefore, this study was aimed at assessing the presence of activated cells in unaffected remote myocardium of patients with acute myocardial infarction (AMI), in comparison to the peri-infarct region from the same cases, and in comparison to myocardial specimens from control hearts. METHODS AND RESULTS: Sixteen patients dying 1 to 12 weeks after AMI and 16 control subjects were selected at autopsy. Myocardial specimens were taken at remote unaffected viable regions and at peri-infarct regions in cases with AMI. Confocal microscopy was performed to measure the number of activated cells (DR+), T-lymphocytes (CD3+), and activated T-lymphocytes (CD3+/DR+). Activated cells and activated T-lymphocytes were found in remote unaffected regions in 11 of 16 cases (69%), in peri-infarct zone in all cases (100%), and in none of the control hearts (0%, P<0.001 versus others). A greater myocardial inflammatory burden in remote regions but not in peri-infarct regions was associated with persistent infarct-related artery occlusion (P<0.05). CONCLUSIONS: This study for the first time shows the presence of activated T-lymphocytes in remote unaffected myocardial regions in approximately two thirds of patients with recent AMI. Because these cells are associated with persistent infarct-related artery occlusion, our data may suggest that an antigenic stimulus present also in the myocardium triggers an immune response that may be critical to precipitate artery occlusion.

Aged↗
PubMed2004

Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction.

OBJECTIVES: We sought to evaluate interleukin-1 receptor antagonist (IL-1Ra) levels in patients with ST-segment elevation acute myocardial infarction (AMI) upon emergency department (ED) admission in order to assess the sensitivity of such a determination by comparison with common markers of myocardial necrosis. BACKGROUND: Inflammatory markers are elevated in patients with unstable coronary syndromes, but IL-1Ra levels during the early phases of AMI have not been previously investigated. METHODS: Levels of IL-1Ra were measured in 44 consecutive patients with AMI and compared with creatine kinase (CK), CK-MB, troponin I, myoglobin, and C-reactive protein (CRP). RESULTS: Upon admission, 82% of patients had elevated (>230 pg/ml) IL-1Ra levels, compared with 41% of patients with raised CK (p = 0.001), CK-MB (45%, p = 0.002), troponin I (57%, p = 0.027), myoglobin (48%, p = 0.004), and CRP (57%, p = 0.019) levels. The IL-1Ra values were significantly higher in patients with heralded AMI than in those without pre-infarction angina (671 vs. 320 pg/ml, p = 0.013). The sensitivity of IL-1Ra determination increased to 86% when chest pain duration was < or =3 h and to 91% if heralded infarction occurred. CONCLUSIONS: Our study indicates that, unlike markers of necrosis, an increase of IL-1Ra levels occurs early in patients with AMI, is more significant in those with heralded infarction and symptom onset < or =3 h, and precedes the release of markers of necrosis. Thus, IL-1Ra determination may be an important early adjuvant toward the diagnosis of AMI in the ED.

Adult↗
PubMed2004

Improved hepatic perfusion after iloprost infusion in patients with HCV chronic infection: a pilot study with possible therapeutic implications.

We performed a pilot study to evaluate whether portal flow volume (PFV) changed in subjects with chronic hepatitis C virus (HCV) infection with respect to control patients after infusion of iloprost, a prostacyclin analog. Six subjects with chronic HCV infection and arteriopathy of the lower limbs (CHCVIA) and 4 control patients affected only by HCV infection (CHCV) were studied with color Doppler sonography. CHCVIA patients were examined before and after 3 days of iloprost infusion, and CHCV patients were examined before and after 3 days with no treatment. In each patient, PFV was obtained after calculating portal flow velocity (PV), portal diameter, and portal vein cross-sectional area. The mean difference between basal and final values of the PFV of CHCVIA patients was significant (p = 0.03), as was the difference in the PFV (final values expressed as percent of basal values) in CHCVIA patients compared with those obtained in the CHCV patients (p = 0.01). We have observed significant improvement in hepatic perfusion in CHCVIA patients compared with CHCV patients after iloprost infusion. In light of these results, we suggest some possible therapeutic implications in patients with HCV infection. Further studies are necessary to confirm this hypothesis.

Epoprostenol↗
PubMed2003

Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure.

OBJECTIVES: The purpose of this study was to evaluate a potential correlation between apoptotic rate (AR), post-infarction left ventricular (LV) remodeling, and clinical characteristics in subjects who died late (>or=10 days) after an acute myocardial infarction (AMI) with evidence of persistent occlusion of the infarct-related artery at autopsy. BACKGROUND: Apoptosis contributes to myocardiocyte loss in cardiac disease and may have a pathophysiologic role in post-infarction LV remodeling. METHODS: The AR was calculated at the site of infarction and in remote unaffected LV regions, using co-localization of in situ end labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3, in 14 subjects who died within two months after AMI. Correlation between AR and clinical characteristics such as age, site of AMI, transmural extension, multivessel coronary disease, and signs and/or symptoms of heart failure (HF), at the time of initial hospitalization for AMI or subsequently before death, was assessed using non-parametric statistical tests. Parameters of LV remodeling including diameters, free wall thickness, diameter-to-wall-thickness ratio, and mass were measured at gross examination at autopsy. Values are expressed as median (interquartile range). RESULTS: Among clinical variables, early symptomatic post-infarction HF (9 cases, 64%) was associated with nearly fourfold increased AR at the site of infarction (26.2% [24.5% to 28.8%] vs. 6.4% [1.9% to 13.3%], p = 0.001). Moreover, AR both at the site of infarction and in unaffected regions was significantly correlated with parameters of progressive LV remodeling (p < 0.05). CONCLUSIONS: Our data show that in patients dying >or=10 days after AMI, myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable LV remodeling and early symptomatic post-infarction HF.

Aged↗
PubMed2003

Hemodynamic effects of a prostacyclin analog (iloprost) on portal flow velocity and volume and visceral artery circulation in patients with lower limb arteriopathy.

Previous studies demonstrated that iloprost improves the peripheral circulation. In this study, we examined, by Doppler sonography, portal flow velocity (cm/s) and volume (mL/min), and resistance index (RI) of visceral arteries in 23 patients before and after 7 days of iloprost infusion. Statistically significant hemodynamic changes were only seen in portal vein (pre-iloprost vs. post-iloprost treatment mean portal flow velocity and volume values: 23.9 cm/s vs. 29.0 cm/s, p < 0.001 and 1824.6 mL/min vs. 2294.4 mL/min, p < 0.001, respectively). On the other hand, the interlobar renal artery RI, reduced after iloprost treatment in most patients, was not statistically significant; conflicting results were obtained on the hepatic and mesenteric arteries. Our results indicate that iloprost significantly increases portal flow velocity and volume. The understanding of the mechanism through which iloprost plays a role in portal microcirculation could be useful for its new medical indications in liver hemodynamic disorders.

Adult↗
PubMed2003

Evidence of CXC, CC and C chemokine production by lymphatic endothelial cells.

Although production of chemokines by vascular endothelial cells has been documented, there is only limited information regarding the expression of chemokines by the lymphatic endothelium. Here we used lymphatic endothelial cells (LEC) derived from experimentally induced murine lymphangiomas to investigate the pattern of chemokine expression by these cells. Histological analysis of the lymphatic hyperplasia revealed the presence of leucocytes in the tissues surrounding the lesions, suggesting the presence of chemoattractant activity. A functional chemotactic assay on human polymorphonuclear cells and on purified subpopulations of murine leucocytes using culture supernatants from LEC primary cultures confirmed the presence of chemoattractant activity. The identity of different cytokines of the CXC, CC and C subfamilies was investigated by reverse trancriptase-polymerase chain reaction on total endothelial cell RNA. Amplified fragments corresponding to KC, IP10, Mig-1, BCL, MIP-2, SLC, RANTES, MCP-1, C10, and Lptn were obtained, and confirmed by Southern blot and sequencing. In contrast, MIP-1alpha, MIP-1beta, and MIP-1gamma were not detected. Higher levels of expression were revealed by Northern blot analysis for Mig-1, MCP-1 and C10. The lymphatic endothelium-restricted production of these chemokines was also confirmed by in situ hybridization. The presence of high C10 mRNA expression levels in LEC was particularly unexpected, because the production of this molecule has been previously identified only in cells of the haematopoietic lineage. These observations represent the first detailed analysis of chemokine production by lymphatic endothelial cells and may account, in part, for the mechanism of leucocyte recruitment into the lymphatics, and of lymphocyte recirculation within the lymphatic system.

Animals↗
PubMed2003

Relevance of interleukin-1 receptor antagonist intron-2 polymorphism in ischemic stroke.

Evidence of inflammatory phenomena associated with atherosclerotic plaques is extensive. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response, and its activity is critically regulated by its receptor antagonist (IL-1Ra). A variable number of tandem repeats (VNTR) in intron 2 of the human IL-1Ra shows a common polymorphism that has been related to different production of IL-1Ra and IL-1 proteins. In monocytes, the less common allele 2 has been associated with an increased production of IL-1Ra and a decreased production of IL-1. Moreover, a cooperative effect with a C to T polymorphism in the promoter of IL-1beta gene (C(-511)-->T) has been described. In the present study, we investigated the frequency of these polymorphisms in 110 subjects who survived an ischemic stroke, in 101 healthy age-matched individuals, and in a population-based sample of 1,303 healthy Italians. The frequency of the IL- 1Ra 1/1 genotype was significantly higher in stroke survivors with respect to age-matched controls (77.2 and 45.5%, respectively; p < 0.001), and to the wide group of healthy Italians (77.2 and 51.9%, respectively; p < 0.001). As expected, the estimated frequency of the IL-1Ra allele 1 (Ra*1 allele) in stroke survivors was higher than in age-matched controls (0.851 and 0.664, respectively; p < 0.001) and in healthy Italians (0.851 and 0.717, respectively; p < 0.001). Thus, ischemic stroke survivors that carry the Ra*1 allele showed a strong association with the disease with respect to age-matched controls [odds ratio (OR) = 3.905; 95% confidence interval (CI), 2.110-7.229] and healthy Italians [OR = 3.256 (95% CI, 1.971-5.379)]. No significant association was seen for the IL-1beta (C(-511)-->T) polymorphism. However, in stroke survivors, an association between the Ra*1 allele and the C allele of the IL-1beta (-511) polymorphism was found (p < 0.001). Our results implicate the IL-1Ra gene in the susceptibility to ischemic stroke, and suggest that IL-1Ra genotyping may be useful in the identification of patient subgroups for pharmacological intervention in IL-1 production or actions.

Adult↗
PubMed2003

Enhanced portal flow velocity and volume following Iloprost treatment.

OBJECTIVE: We studied, with color Doppler sonography, portal flow velocity (PV) and volume (PFV) before and after Iloprost infusion. BACKGROUND: Iloprost is a prostacyclin analogue with arterial vasodilator and platelet aggregation inhibitor properties. Recently, hemodynamic effects after treatment with Iloprost have been demonstrated in subjects with arteriopathy of lower limbs. METHODS: We treated 10 subjects (2 males and 8 females; mean age 64 +/- 8.2 years) affected by arteriopathy of lower limbs with intravenous infusion of Iloprost, at a dosage of 2 ng/Kg/min (16 hours/day) for 3 days. In all patients portal vein flow velocity (PV) (cm/s) and volume (PFV) (ml/min) were assessed. PV was directly determined by the Doppler system, whereas PFV was calculated using the formula "CSA x PV", after measuring the portal vein cross sectional area (CSA) (mm2). RESULTS: The patients showed markedly increased PV and PFV after Iloprost infusion (pre-Iloprost vs post-Iloprost treatment mean portal flow velocity and volume values: 23.12 +/- 3.89 cm/s vs 28.49 +/- 3.90 cm/s, p < 0.01 and 1743.9 +/- 241.7 ml/min vs 2271.7 +/- 333.5 ml/min, p < 0.001, respectively). CONCLUSIONS: This study confirms our previous results about increased PV and PFV values after Iloprost treatment. In the light of these results we suggest some possible therapeutic implications in patients undergoing liver transplantation. However, further studies are necessary to confirm this hypothesis.

Aged↗
PubMed2002

Prognostic value of interleukin-1 receptor antagonist in patients undergoing percutaneous coronary intervention.

Elevated plasma levels of inflammatory markers, such as C-reactive protein (CRP), have been associated with adverse outcome in selected patients with coronary artery disease (CAD) treated with coronary angioplasty or stenting. The aim of this study was to evaluate the predictive value of preprocedural interleukin-1 receptor antagonist (IL-1Ra) plasma levels for long-term major adverse cardiac events (MACE) in a series of unselected patients with symptomatic CAD treated with percutaneous coronary intervention (PCI). Seventy-three consecutive patients (62 men, aged 62 +/- 9 years) undergoing PCI were enrolled in a prospective follow-up study. IL-1Ra and CRP plasma levels were measured before the procedure; 36 patients (49%) had unstable angina pectoris on admission, 37 (51%) had chronic stable angina pectoris, and 30 (41%) had multivessel CAD, 15 of whom underwent multivessel PCI. Success was achieved in all 73 patients, with coronary stenting performed in 63 (86%). Follow-up clinical assessment included occurrence of MACE at 3, 6, 12, and 18 months. Logistic regression analysis, performed to determine independent predictors of MACE, identified IL-1Ra levels in the upper quartile as the only independent predictive factor of MACE at 18 months (19% in the fourth quartile vs 0% in the first quartile; p = 0.032). Patients with high preprocedural CRP levels (fourth quartile) had a nonsignificant increased risk of MACE (p = 0.09). Thus, preprocedural IL-1Ra plasma levels appear to be a valuable independent predictive factor of MACE in unselected patients undergoing PCI.

Aged↗
PubMed2002

Cytolytically inactive terminal complement complex causes transendothelial migration of polymorphonuclear leukocytes in vitro and in vivo.

Intravital microscopy was used to monitor leukocyte traffic across rat mesenteric postcapillary venules induced by the inactive terminal complement (C) complex (iTCC) topically applied to ileal mesentery. Leukocytes started rolling within 15 minutes from the administration of iTCC, and by 1 hour they adhered almost completely to the endothelium emigrating from the vessels in the next 3 hours. C5a caused a similar, though less marked, effect, whereas boiled iTCC was inactive, excluding the contribution of contaminating lipopolysaccharide. The complex stimulated the migration of polymorphonuclear neutrophils (PMNs) across endothelial cells (ECs) in a transwell system after a 4-hour incubation of ECs with iTCC added to the lower chamber of the transwell, whereas a 30-minute incubation was sufficient for C5a and interleukin (IL)-8 to induce the passage of PMNs. C5a was not responsible for the effect of iTCC because this complex had no chemotactic activity and contained too small an amount of C5a to account for the transendothelial migration of PMNs. Similarly, the effect of iTCC was not mediated by IL-8 released by stimulated ECs because anti-IL-8 failed to inhibit the migration of PMNs induced by the complex. Unlike tumor necrosis factor-alpha, iTCC did not cause the redistribution of platelet-endothelial cell adhesion molecule-1 (PECAM-1), and PMN mobilization was partially blocked by anti-PECAM-1 antibodies.

Animals↗
PubMed2002

Inflammatory markers and coronary interventions: a potentially useful follow-up modality after stenting.

Periprocedural levels of various inflammatory markers have been correlated with prognosis in patients undergoing percutaneous coronary interventions. However, long-term variations of interleukin-1 receptor antagonist (IL-1Ra) or C-reactive protein (CRP) during follow-up after coronary interventions were not previously investigated. The aim of our study was to perform serial evaluations of these markers before and after coronary stenting and to correlate them with clinical status. Plasma levels of IL-1Ra and CRP were measured at baseline and 3 and 6 months after the procedure in 31 patients with symptomatic coronary artery disease undergoing stent implantation, who had no evidence of myocardial ischemia at 6-month follow-up. While at 3 months there were no significant variations of baseline values, 6 months after the procedure a significant decrease from baseline was observed both in IL-1Ra and CRP levels (median -24 pg/ml, P = 0.048, and -0.13 mg/dl, P = 0.017, respectively). Six-month reduction in both IL-1Ra and CRP levels was significant in patients with unstable angina (n = 18; IL-1Ra: from 175 to 119 pg/ml, P = 0.001; CRP: from 0.52 to 0.18 mg/dl, P = 0.002) and nonsignificant in those with stable angina (n = 13) on admission (IL-1Ra: from 123 to 158 pg/ml, P = 0.22; CRP: from 0.19 to 0.10 mg/dl, P = 0.44). In conclusion, a significant reduction of IL-1Ra and CRP levels is observed 6 months after stent implantation in patients with preprocedural unstable angina who remain free of ischemia. This decrease suggests a stabilization of the inflammatory process and may be associated with a favorable prognosis after coronary interventions.

Aged↗