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Biomedical subjects

Stefania Basili

Publications and source records attributed to Stefania Basili.

At least 19 recordsLinked to original sources
PubMed2006

Insulin resistance as a determinant of platelet activation in obese women.

OBJECTIVES: We tested the hypothesis that insulin resistance, per se, contributes to increased platelet activation in obesity, independently of underlying inflammation. BACKGROUND: Obesity, insulin resistance, and atherosclerosis are closely linked phenomena associated with low-grade inflammation. Obesity is associated with persistent platelet activation in otherwise healthy women. METHODS: We performed a cross-sectional study in 40 obese and 20 non-obese healthy women using urinary thromboxane metabolite excretion as a non-invasive index of platelet activation. An index of insulin sensitivity, S(I), and plasma adiponectin, C-reactive protein (CRP), and CD40 ligand (CD40L) levels were measured. RESULTS: Obese women had significantly (p < 0.0001) higher 11-dehydro-thromboxane B2 (11-dehydro-TXB2) excretion (median 718 vs. 211 pg/mg creatinine), CRP (1.13 vs. 0.48 mg/l), and CD40L levels (4.45 vs. 0.90 ng/ml) than controls. Obese women had lower S(I) (median 2.51 vs. 5.0 10(4) min(-1)/[microU/ml], p < 0.002) and adiponectin (6.3 vs. 10 microg/ml, p < 0.01) than control subjects. On multiple regression analysis, waist-to-hip ratio (beta = 0.27, p < 0.05) and S(I) (beta = -0.72, p < 0.04) predicted 11-dehydro-TXB2 excretion rate, independently of adiponectin, CRP, CD40L, and lipid patterns. In order to investigate the cause-effect relationship of these associations, we examined the effects of a 12-week weight loss program or a 3-week pioglitazone treatment on urinary 11-dehydro-TXB2 in 10 women with impaired S(I) and visceral obesity. Successful weight loss (0.6 kg loss/week) achieved in 5 subjects was associated with increased S(I) (+92%) and decreased CD40L (-27%), CRP (-37%), and 11-dehydro-TXB2 (-53%) (p < 0.05). Consistently, improvement of insulin sensitivity achieved with pioglitazone significantly decreased urinary 11-dehydro-TXB2 excretion (-43%, p < 0.05) without changes in body weight. CONCLUSIONS: Insulin resistance is a major determinant of platelet activation in female obesity.

Adult↗
PubMed2006

Low-density lipoprotein-lowering medication and platelet function.

Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) levels represent one of the most important risk factors for atherosclerosis and therefore cardiovascular morbidity and mortality. LDL-C operates at different levels and through various classic and non-classic mechanisms. In particular, increased or modified LDL enhances platelet function and increases sensitivity of platelets to several naturally occurring agonists. Agents that lower LDL-C in hypercholesterolemic patients have been shown to interfere with platelet function. Several studies, in fact, suggested that statins exert anti-thrombotic effects largely as a result of an anti-platelet activity. Among the other LDL-C-lowering agents those acting by interfering with cholesterol reabsorption from the gut (cholestyramine, colestipol) do not appear to interfere with platelet function, whereas peroxisome proliferator-activated receptor agonists (such as fibrates) can inhibit platelet function. The full potential of these drugs in vascular protection is only just being realized. Further studies are still needed to elucidate the full therapeutic benefits of these agents in plaque stabilization and thrombosis.

Anticholesteremic Agents↗
PubMed2005

Thromboxane-dependent CD40 ligand release in type 2 diabetes mellitus.

OBJECTIVES: The goals of this study were to characterize the platelet contribution to soluble CD40 ligand (sCD40L), to correlate its formation with the extent of oxidative stress and platelet activation, and to investigate the effects of improved metabolic control and low-dose aspirin on these processes. BACKGROUND: Inflammation, oxidative stress, and platelet activation are involved in the pathogenesis of type 2 diabetes (T2DM) and its complications. The CD40-CD40L interactions result in inflammatory and pro-thrombotic responses. METHODS: Urinary 8-iso-prostaglandin (PG)F2alpha and 11-dehydro-thromboxane (TX)B2, in vivo markers of oxidative stress and platelet activation, respectively, plasma CD40L, and C-reactive protein (CRP) were measured in 114 T2DM patients and 114 control patients. A randomized, parallel group, 17-day study of aspirin (30, 100, or 325 mg/day) was performed in 18 T2DM patients. A similar study was performed in six healthy volunteers (aspirin, 100 mg/day). Twenty poorly controlled T2DM patients were studied before and after improved metabolic control. RESULTS: Compared with control patients, diabetic patients showed significantly higher levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, sCD40L, and CRP. On multiple regression analysis, 11-dehydro-TXB2 and 8-iso-PGF2alpha excretion rates predicted sCD40L levels. Soluble CD40L linearly correlated with 11-dehydro-TXB2 (rho = 0.67, p < 0.0001), and both were reduced after one week of aspirin (p < 0.0026), with slow recovery over 10 days after aspirin withdrawal. Improved metabolic control was associated with a reduction in sCD40L, 8-iso-PGF2alpha, and 11-dehydro-TXB2. CONCLUSIONS: This study provides several lines of evidence for the dependence of sCD40L release on TXA(2)-dependent platelet activation in T2DM and provides novel mechanistic insight into the amplification loops of persistent platelet activation in this setting.

Aged↗
PubMed2005

Soluble CD40L and cardiovascular risk in asymptomatic low-grade carotid stenosis.

BACKGROUND AND PURPOSE: We investigated whether soluble CD40L (sCD40L) may predict the risk of cardiovascular (CV) events in patients with asymptomatic carotid plaques. METHODS: Forty-two patients with asymptomatic low-grade carotid stenosis (ALCS) and 21 controls without any carotid stenosis were enrolled. All subjects had at least a major cardiovascular risk factor (CRF). Plasma levels of C-reactive protein (CRP), IL-6, and sCD40L were measured. Subjects were reviewed every 12 months (median follow-up, 8 years). RESULTS: ALCS patients had higher (P<0.0001) CRP, IL-6, and sCD40L than controls. Fourteen patients experienced a CV event. Cox regression analysis showed that only high sCD40L levels (P=0.003) independently predicted cardiovascular risk. CONCLUSIONS: High levels of sCD40L may predict the risk of CV events in ALCS.

C-Reactive Protein↗
PubMed2005

High resolution ultrasonography in detection of bone erosions in patients with hand osteoarthritis.

OBJECTIVE: To evaluate the ability of high resolution ultrasonography (US) in the diagnosis of erosive osteoarthritis (OA). METHODS: We enrolled 110 patients with signs and symptoms of inflammatory OA. Radiographs of both hands were performed in all patients; 22 were diagnosed as having erosive OA and 88 classical OA on the basis of typical erosive/non-erosive patterns. Distal and proximal interphalangeal joints of all patients were evaluated by US by 2 independent operators blinded to patient data. The examination was performed with a multiplanar scan technique, with joints in both maximal extension and flexion, using either a 14 MHz or 8-16 MHz broadband linear probe. The presence of articular bone surface irregularities defined as either marginal osteophytes or central erosions was recorded. Sensitivity, specificity, and likelihood ratios on the presence of erosions were calculated. RESULTS: Central erosions were detected by US in 16 of 22 (72.7%) patients with erosive OA and in none of 88 patients with classical hand OA. Sensitivity and specificity for the detection of central erosions by US were 73% and 100%, respectively. The positive and negative likelihood ratios were 100% and 94%. CONCLUSION: This is the first study to evaluate the presence of erosions in patients with erosive OA by US. Our results showed good concordance between US and radiography in detecting central joint erosions. We believe US may be considered a useful technique for the differential diagnosis between erosive OA and classical hand OA.

Aged↗
PubMed2004

Helicobacter pylori infection causes persistent platelet activation in vivo through enhanced lipid peroxidation.

OBJECTIVE: We aimed at investigating the relationship between Helicobacter pylori infection and in vivo lipid peroxidation and platelet activation, as reflected by urinary 8-iso-prostaglandin (PG)F(2alpha) and 11-dehydro-thromboxane (TX)B2, respectively, in otherwise healthy dyspeptic subjects. METHODS AND RESULTS: We measured urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 excretion in 40 dyspeptic subjects with a positive 13C-urea breath test and 38 dyspeptic individuals with a negative test. Moreover, we investigated the effects of H pylori eradication on prostanoid metabolite excretion in 23 H pylori-positive subjects. We also measured prostanoid metabolite excretion before and after selective cyclooxygenase-2 inhibition with rofecoxib in 4 H pylori-positive subjects. Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 excretion was significantly higher in the H pylori-positive individuals than in controls. A significant direct correlation was found between the degree of positivity to the 13C-urea breath test and urinary 8-iso-PGF2alpha excretion. The latter was linearly correlated with urinary 11-dehydro-TXB2. Successful eradication of H pylori infection led to a significant reduction in both 8-iso-PGF(2alpha) and 11-dehydro-TXB2. Furthermore, their levels were unaffected after treatment with rofecoxib. CONCLUSIONS: Our study provides evidence of enhanced in vivo lipid peroxidation and platelet activation in association with H pylori infection and suggests a novel mechanism by which an infectious agent could contribute to atherothrombosis.

Adult↗
PubMed2004

Prognostic value of soluble P-selectin levels in colorectal cancer.

Measurement of soluble (s) P-selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP-selectin in association with clinicopathological variables in 181 patients with primary (n =149) or metastatic (n = 32) colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP-selectin levels were higher in patients with CRC compared either to patients with benign disease (p = 0.006) or controls (p = 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP-selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p = 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP-selectin (regression coefficient = 0.28, p < 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP-selectin levels had an independent prognostic role in predicting recurrent disease (HR = 2.22, p = 0.019) and mortality from CRC (HR = 3.44, p= 0.017). These results suggest that measurement of plasma sP-selectin might represent a prognostic indicator in the management of patients with CRC.

Adult↗
PubMed2004

Soluble CD40 ligand plasma levels in lung cancer.

PURPOSE: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.

Adenocarcinoma↗
PubMed2004

Oxidant stress and platelet activation in hypercholesterolemia.

Hypercholesterolemia is the dominant risk factor associated with atherothrombotic disorders in the western world. Consequently, much attention has been devoted to defining its role in the pathogenesis of atherosclerosis. It is currently recognized that hypercholesterolemia induces phenotypic changes in the microcirculation that are consistent with oxidative and nitrosative stresses. Superoxide is generated via several cellular systems and, once formed, participates in a number of reactions, yielding various free radicals, such as hydrogen peroxide, peroxynitrite, or oxidized low-density lipoproteins. Once oxidant stress is invoked, characteristic pathophysiologic features ensue, such as platelet activation and lipid peroxidation, which are both involved in the initiation and progression of the atherosclerotic lesions. Thus, therapeutic strategies that act to maintain the normal balance in the oxidant status of the vascular bed may prove effective in reducing the deleterious consequences of hypercholesterolemia.

Antioxidants↗
PubMed2004

Absolute neutrophil counts and fibrinogen levels as an aid in the early diagnosis of acute myocardial infarction.

A retrospective analysis of white blood cell (WBC) counts and fibrinogen levels was performed on 292 consecutive patients admitted to the emergency department for chest pain likely due to ischaemic heart disease. Aims of the study were to evaluate their utility in discriminating between cardiac and non-cardiac chest pain, and to identify those "chest pain-enzyme negative" patients who are at high risk of developing acute myocardial infarction (AMI). The results obtained showed that WBC (p < 0.0001) and fibrinogen (p < 0.0001) significantly discriminated AMI patients. However, only male gender (p < 0.03), abnormal CK-MB% (p < 0.0001) and neutrophil counts (p < 0.0001) were independently related to AMI. The combined determination of neutrophils and CK-MB% increased the sensitivity from 50% (for CK-MB% alone) to 70% (p < 0.05), with a negative predictive value similar to that observed for CK-MB% alone. These results suggest that determination of neutrophil counts might help to improve the accuracy of AMI diagnosis in emergency patients.

Adult↗
PubMed2004

[New insights in the pathogenesis of prothrombotic state associated with hypercholesterolemia].

Hypercholesterolemia and overt atherosclerotic disorders have been associated with a low-grade inflammation that involves not only the intrinsic cells of the artery wall, but also circulating cells. Platelets as well as monocytes participate importantly in this disease process through the release of a wide variety of biologically active substances. Recent findings on the inflammatory actions of platelets have opened new perspectives in the comprehension of the pathogenetic mechanism(s) of atherosclerosis. Stimulated platelets, in fact, actively synthesize proinflammatory cytokines which have been all involved in the inflammatory process associated to hypercholesterolemia and plaque development. In this context, increasing evidence suggests that interrelated inhibition of inflammation and thrombosis induced by statins could largely contribute to clinical benefits from lipid-lowering therapy.

Arteriosclerosis↗
PubMed2003

Enhanced interleukin-1beta in hypercholesterolemia: effects of simvastatin and low-dose aspirin.

BACKGROUND: This study was aimed at verifying whether activation of platelets might represent a source of interleukin (IL)-1beta levels in hypercholesterolemia. To this purpose, we compared the effects of a short-term treatment with simvastatin or low-dose aspirin on circulating levels of this cytokine. METHODS AND RESULTS: Fifty patients with hypercholesterolemia were randomly allocated to receive an 8-week therapeutic course of simvastatin 20 mg daily (n=25) or aspirin 100 mg daily (n=25). Baseline soluble (s) P-selectin directly correlated with IL-1beta (P<0.0001) and C-reactive protein (CRP) (P<0.05) but not with von Willebrand factor, total cholesterol, or LDL cholesterol levels. Furthermore, sP-selectin (P<0.02) and IL-1beta (P<0.0001) levels were independently related to CRP by multiple regression analysis. Both drugs were associated with comparable, significant reductions in IL-1beta and sP-selectin. Simvastatin, but not aspirin treatment, significantly lowered CRP levels (P<0.05). The change in IL-1beta levels correlated with the change in sP-selectin in patients randomized to either simvastatin (Rho, 0.42; P<0.05) or aspirin (Rho, 0.42; P<0.05). In contrast, the simvastatin-induced change in IL-1beta did not correlate with the change in CRP levels. CONCLUSIONS: This study suggests that platelets might contribute to IL-1beta production in hypercholesterolemia, thus providing an additional link between inflammation and the prothrombotic state in this setting.

Adult↗
PubMed2003

Enhanced lipid peroxidation and platelet activation in the early phase of type 1 diabetes mellitus: role of interleukin-6 and disease duration.

BACKGROUND: To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A2 biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F2-isoprostane formation in this setting. METHODS AND RESULTS: A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM ( 1 year, group B). Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 were measured in all patients and in age- and gender-matched controls. Circulating interleukin-6 (IL-6), tumor necrosis factor-alpha, and C-reactive protein were also determined as markers of the inflammatory response. Fifteen of the 23 children in group A were reexamined after 12 months. Compared with either controls or group B, diabetic children in group A showed significantly higher levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, IL-6, tumor necrosis factor-alpha, and C-reactive protein. Statistically significant correlations between IL-6 and both 8-iso-PGF2alpha (r=0.63, P<0.001) and 11-dehydro-TXB2 (r=0.51, P<0.01) were observed. The 15 patients reexamined after 1 year showed a significant reduction in lipid peroxidation and platelet activation (P<0.02 and P<0.001, respectively), consistent with reduced levels of IL-6 and tumor necrosis factor-alpha. CONCLUSIONS: These results demonstrate that enhanced lipid peroxidation and platelet activation represent early events in T1DM that are possibly related to an acute inflammatory response. These noninvasive indexes may help in further examining T1DM pathophysiology and monitoring pharmacological interventions to interfere with disease development and progression.

Adolescent↗
PubMed2003

Increased circulating Interleukin-18 levels in centenarians with no signs of vascular disease: another paradox of longevity?

Interleukin (IL)-18 is highly expressed in macrophages from human atherosclerotic plaques, suggesting its involvement in ischemic syndromes. We evaluated IL-18 and IL-18 binding protein (BP) in healthy centenarians, as longevity is characterized by a reduced incidence of ischemic events. For comparison, patients with chronic ischemic syndromes (CIS) were evaluated. Serum IL-18 and IL-18BP levels were measured by non-cross-reacting ELISA in 16 healthy centenarians and in two age-control populations, each of 18 healthy individuals aged 55.9+/-1.43 and 74.3+/-1.35, respectively, as well as in 23 CIS patients, and another cohort of 23 healthy subjects that were age- and sex-matched with CIS patients. Centenarians displayed significantly higher total IL-18 serum levels compared to each control group. Elevated IL-18 levels were also present in CIS patients. However, centenarians had a significant higher level of IL-18BP compared to the cohort of 23 controls (P=0.0014), and compared to CIS patients (P=0.043); as a result centenarians exhibited a lower level of free IL-18 than CIS patients. The present results indicate that quenching of IL-18 by IL-18BP may explain the apparent paradox of elevated serum IL-18 with no vascular signs in centenarians.

Aged↗
PubMed2003

Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker of inflammation.

BACKGROUND: The finding that expression of metalloproteinases (MMPs) is induced in atherosclerotic plaques prone to rupture suggests the possibility that patients with atherosclerotic diseases would show enhanced blood levels of MMPs and that MMPs might represent a potential inflammatory risk factor for atherosclerosis. Therefore, the present study was aimed at verifying whether MMPs may represent sensitive markers of inflammation in patients with coronary artery disease. METHODS: MMP-2, MMP-9, interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen levels were measured in blood samples obtained from 66 cases with previous acute myocardial infarction and 66 control subjects similar for age, sex, and major atherosclerotic risk factors but without history or evidence of atherothrombotic diseases. RESULTS: Biohumoral markers of inflammation and MMP-9 levels were significantly elevated in cases compared with controls (median values 40.6 versus 9.8 ng/mL; p < .0001), whereas MMP-2 levels did not differ between the two groups (median values 839 versus 873 ng/mL; p = .53). A direct correlation was found among MMP-9, CRP, IL-6, and fibrinogen levels. Conditional logistic regression analysis showed that MMP-9 is related to myocardial infarction (p = .006) even after adjusting for cardiovascular medications and CRP. CONCLUSION: These findings suggest that measurement of serum MMP-9 levels may represent a novel marker of inflammation in patients with known coronary artery disease and might provide an index of plaque activity in this clinical setting.

Aged↗
PubMed2003

Association between serum carcinoembryonic antigen and endothelial cell adhesion molecules in colorectal cancer.

OBJECTIVES: To analyse the behaviour of pre-surgical serum levels of soluble (s)E-selectin and vascular cell adhesion molecule (sVCAM) in patients with colorectal cancer, and to evaluate their possible correlation with carcinoembryonic antigen (CEA), pro-inflammatory cytokines and clinicopathological features with respect to their prognostic value in predicting metastatic disease. METHODS: Pre-surgical serum levels of sE-selectin, sVCAM, interleukin-6 (IL-6), IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and CEA were measured in 194 patients with colorectal adenocarcinoma, 40 patients with benign colorectal diseases and 59 healthy subjects. RESULTS: sE-selectin, sVCAM, TNF-alpha and IL-6 levels were significantly higher in patients with colorectal cancer compared to either healthy subjects or patients with benign disease. Positive rates of sE-selectin, sVCAM and TNF-alpha levels were significantly associated with Dukes' stage D colorectal cancer, and all three variables were independently associated to the presence of distant metastases. Positive sE-selectin, sVCAM and TNF-alpha levels were significantly associated to CEA. TNF-alpha and CEA levels were independently related to the presence of positive levels of sE-selectin and/or sVCAM. CONCLUSIONS: Our findings suggest that the host inflammatory response to cancer cells, and/or their released products (i.e. CEA), might be responsible (via cytokine release) for the elevation in circulating adhesion molecules in patients with colorectal cancer.

Adult↗
PubMed2003

Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women.

Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index > or = 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-beta 1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control subjects or NIS patients. On the other hand, NIS patients had higher CRP, TGF-beta 1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-beta 1, CRP, PAI-1, factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-beta 1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-beta 1 and the insulin sensitivity index were independently related to F1 + 2. Our results are the first to document an in vivo relationship between insulin sensitivity and coagulative activation in obesity. The elevated TGF-beta 1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease.

Adult↗