244 results on '"Ciccarelli L."'
Search Results
52. Low leakage design of LUT-based FPGAs.
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Lodi, A., Ciccarelli, L., Loparco, D., Canegallo, R., and Guerrieri, R.
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- 2005
- Full Text
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53. On the efflciency of error concealment techniques in H.264/AVC coders.
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Chiaraluce, F., Ciccarelli, L., Gambi, E., and Spinsante, S.
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- 2005
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54. Low leakage circuit design for FPGAs.
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Ciccarelli, L., Lodi, A., and Canegallo, R.
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- 2004
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55. High efficiency separator for natural gas processing
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Spinelli, U., Ciccarelli, L., and Bennardo, A.
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Oil and gas field equipment industry -- Product information ,Business ,Petroleum, energy and mining industries - Abstract
The 'Wringing separator' is a system designed and supplied by Italy's Micronsep S.r.l. to separate very small particles from gas feed. The minimum size of the solids particles is 1 [...]
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- 2005
56. Decoder-based multi-context interconnect architecture.
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Lodi, A., Ciccarelli, L., Cappelli, A., Carnpi, F., and Toma, M.
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- 2003
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57. A quantum mechanical test of the DIM surface of the Li + HCl semi-empirical surface
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Ciccarelli, L., Garcia, E., and Lagana', Antonio
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- 1985
58. Abstraction and exchange contributions to the rate constants of Muonium + Hydrogen Chloride reaction
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Lagana', Antonio and Ciccarelli, L.
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- 1987
59. A parametrization of reactive rates for H + H2 (v≤7) reaction
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Ciccarelli, L. and Lagana', Antonio
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- 1988
60. Fast mode decision strategies for the use of high definition in H.264/AVC based videoconference applications
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Spinsante, S., Ciccarelli, L., Gambi, E., Beccacece, D., Franco Chiaraluce, and Falasconi, C.
61. Performance evaluation of error concealment techniques in H.264 video coding
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Chiaraluce, F., Ciccarelli, L., Ennio Gambi, and Spinsante, S.
62. On the efficiency of error concealment techniques in H.264/AVC coders
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Franco Chiaraluce, Ciccarelli, L., Gambi, E., and Spinsante, S.
63. Metabolic variations with oral antidiabetic drugs in patients with Type 2 diabetes: comparison between glimepiride and metformin
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Giuseppe Derosa, Franzetti I, Gadaleta G, Ciccarelli L, and Fogari R
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Blood Glucose ,Glycated Hemoglobin ,Male ,Fasting ,Middle Aged ,Metformin ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,Food ,Plasminogen Activator Inhibitor 1 ,Humans ,Hypoglycemic Agents ,Female ,Homocysteine ,Aged ,Lipoprotein(a) - Abstract
Patients with Type 2 diabetes (T2DM) are at high risk of morbidity and mortality from cardiovascular complications, and hypoglycaemia increases this risk. Furthermore, other metabolic parameters exacerbate cardiovascular risk in these patients. The aim of the study was to compare the metabolic effects of glimepiride and metformin in patients with T2DM. We evaluated 164 patients with T2DM (80 males, 84 females) in a multicentre, randomised, controlled, open, parallel group study comparing glimepiride with metformin. Eighty-one patients (aged 56+/-10 yr) received glimepiride (3+/-1 mg/d); 83 patients (aged 58+/-9 yr) received metformin (2500+/-500 mg/d). Patients had been diagnosed foror = 6 months; they were non-smokers; had no hypertension or coronary heart disease; were not taking hypolipidaemic drugs, diuretics, beta-blockers or thyroxin; and had normal renal function. Metabolic parameters were measured after 6 and 12 months of treatment. Glimepiride significantly lowered lipoprotein(a) [Lp(a)] and homocysteine levels (HCT) at 6 and 12 months. Both glimepiride and metformin lowered plasminogen activator inhibitor Type 1 (PAI-1) at 12 months and significantly improved levels of glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose after 6 and 12 months. Metformin significantly lowered fasting plasma insulin and postprandial plasma insulin. Glimepiride and metformin also reduced levels of other metabolic parameters in patients with T2DM. In particular, glimepiride significantly reduced HCT, Lp(a), and PAI-1 levels, important metabolic risk factors for atherosclerotic vascular disease. These reductions may be owing to improved glucose metabolism, but it cannot be excluded that these drugs have a direct effect on additional metabolic parameters.
64. A quantum-mechanical test for a LiHCl semi-empirical surface
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Ciccarelli, L., primary, Garcia, E., additional, and Laganà, A., additional
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- 1985
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65. Deactivation of vibrationally excited nitrogen molecules by collision with nitrogen atoms
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Lagana, A., primary, Garcia, E., additional, and Ciccarelli, L., additional
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- 1987
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66. A parametrization of reactive rates for hydrogen atom + hydrogen(.upsilon..ltoreq.7) reaction
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Ciccarelli, L., primary and Lagana, A., additional
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- 1988
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67. Low leakage circuit design for FPGAs
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Ciccarelli, L., primary, Lodi, A., additional, and Canegallo, R., additional
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68. Decoder-based multi-context interconnect architecture
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Lodi, A., primary, Ciccarelli, L., additional, Cappelli, A., additional, Carnpi, F., additional, and Toma, M., additional
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- View/download PDF
69. Low leakage design of LUT-based FPGAs
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Lodi, A., primary, Ciccarelli, L., additional, Loparco, D., additional, Canegallo, R., additional, and Guerrieri, R., additional
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70. A Case-Study on Multimedia Applications for the XiRisc Reconfigurable Processor
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Mucci, C., primary, Bocchi, M., additional, Gagliardi, P., additional, Ciccarelli, L., additional, Lodi, A., additional, Toma, M., additional, and Campi, F., additional
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71. XiSystem: a XiRisc-based SoC with a reconfigurable io module
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Cappelli, A., primary, Lodi, A., additional, Bocchi, M., additional, Mucci, C., additional, Innocenti, M., additional, De Bartolomeis, C., additional, Ciccarelli, L., additional, Giansante, R., additional, Deledda, A., additional, Campi, F., additional, Toma, M., additional, and Guerrieri, R., additional
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72. An Embedded Reconfigurable Datapath for SoC
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Lodi, A., primary, Ciccarelli, L., additional, Mucci, C., additional, Giansante, R., additional, Cappelli, A., additional, and Toma, M., additional
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73. An embedded reconfigurable datapath for SoC.
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Lodi, A., Ciccarelli, L., Mucci, C., Giansante, R., and Cappelli, A.
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- 2005
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74. XiSystem: a XiRisc-based SoC with a reconfigurable IO module.
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Cappelli, A., Lodi, A., Bocchi, M., Mucci, C., Innocenti, M., De Bartolomeis, C., Ciccarelli, L., Giansante, R., Deledda, A., Campi, F., Toma, M., and Guerrieri, R.
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- 2005
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75. Modified twofish algorithm for increasing security and efficiency in the encryption of video signals.
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Catalini, G., Chiaraluce, F., Ciccarelli, L., Gambi, E., Pierleoni, P., and Reginelli, M.
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- 2003
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76. A randomized, double-blind, controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes mellitus.
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Derosa G, Cicero AFG, Ciccarelli L, and Fogari R
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Background: When choosing an antihypertensive drug for patients with hypertension and diabetes mellitus (DM), the metabolic side effects, possibility of improving some metabolic parameters, and need for adequate blood pressure control must all be considered.Objective: The goal of this study was to compare the impacts of perindopril and candesartan on blood pressure, glucose metabolism, serum lipid profile, and metabolic parameters in patients with mild hypertension and type 2 DM during therapy and after a 1-month washout period.Methods: Type 2 DM patients with mild hypertension and good glucose control who were not taking hypercholesterolemic drugs were enrolled. Perindopril 4 mg QD or candesartan 16 mg QD was administered for 12 months in this randomized, double-blind, controlled, parallel-group clinical trial. Fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin, homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, lipoprotein(a) (Lp[a]), plasminogen activator inhibitor 1 (PAI-1), homocysteine, body mass index (BMI), and albumin excretion rate (AER) were assessed.Results: Ninety-six patients (49 women and 47 men; mean [SD] ages, 53 [10] years [perindopril] and 55 [9] years [candesartan]) were enrolled. Mean (SD) body weight, height, and BMI were 78.2 (9.4) kg, 1.69 (0.05) m, and 27.2 (2.0) kg/m2 in the perindopril group and 77.5 (8.6) kg, 1.70 (0.06) m, and 26.8 (2.5) kg/m2 in the candesartan group. A significant change occurred from baseline to month 12 during treatment with perindopril in SBP and DBP (both P < 0.01), FPG (P < 0.05), FPI (P < 0.05), TC (P < 0.05), LDL-C (P < 0.05), Lp(a) (P < 0.05), PAM (P < 0.05), and AER (P < 0.05). Significant changes from baseline to month 12 occurred with candesartan in SBP and DBP (both P < 0.01) and AER (P < 0.05). The HOMA index was significantly lower at month 12 in the perindopril group than in the candesartan group (P < 0.05). When we interrupted perindopril and candesartan therapy for a 1-month washout period, changes in SBP and DBP values were significant compared with month 12 in both groups (all P < 0.05). Changes in TC and LDL-C from month 12 to the end of washout were significant only in the perindopril group (both P < 0.05).Conclusions: Perindopril and candesartan both effectively lowered blood pressure in this group of patients with mild hypertension and type 2 DM. Perindopril showed an improvement on some metabolic parameters compared with candesartan. However, the inclusion/exclusion criteria could limit the ability to extrapolate the results to a general population. [ABSTRACT FROM AUTHOR]
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- 2003
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77. Randomized, double-blind, placebo-controlled comparison of the action of orlistat, fluvastatin, or both on anthropometric measurements, blood pressure, and lipid profile in obese patients with hypercholesterolemia prescribed a standardized diet.
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Derosa G, Mugellini A, Ciccarelli L, and Fogari R
- Abstract
OBJECTIVE: The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a standardized diet, comparing the action of orlistat, fluvastatin, orlistat with fluvastatin, and placebo on anthropometric measurements, blood pressure (BP), and lipid profile. METHODS: This was a 1-year, randomized, double-blind, placebo-controlled trial. The patients were prescribed a controlled-energy diet and were randomly allocated to receive placebo, orlistat 120 mg TID (O group), fluvastatin 80 mg/d (F group), or olistat 120 mg TID with fluvastatin 80 mg/d (OF group). Clinical measurements (body weight, body mass index [BMI], waist circumference, and BP) and lipid profile assessment (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TGs]) were performed at baseline and after 6 months and 1 year of treatment. RESULTS: The study included 99 obese patients with hypercholesterolemia (48 men and 51 women; mean [SD] age, 51 [9] years). There were no significant differences between groups in baseline demographic, BP, or plasma lipid values. Three patients dropped out (2 women in the O group and 1 man in the OF group) due to adverse events related to orlistat treatment, including gastrointestinal events (oily spotting and fecal urgency). Ninety-six patients completed the study. There were significant differences from baseline (mean [SD]) in BMI, waist circumference reduction (WCR), and body weight loss (BWL) at 6 months in the OF group (29.9 [1.1] kg/m(2), 2.7 [0.8] cm, and 7.4 [0.9] kg, respectively; all P < 0.05), and BMI, WCR, and BWL at 1 year in the O group (29.0 [1.0] kg/m(2), 3.0 [1.0] cm, and 8.6 [1.0] kg, respectively; all P < 0.02), the F group (29.3 [1.6] kg/m(2), 2.4 [1.0] cm, and 8/0 [1.0] kg, respectively; all P < 0.05), and the OF group (28.4 [0.6] kg/m(2), 4.0 [0.6] cm, and 11.4 [1.0] kg, respectively; all P < 0.01). Significant reductions from baseline in systolic and diastolic BP were observed at 1 year in the O and F groups (all P < 0.05) and the OF group (both P < 0.01). At 6 months, there were significant reductions from baseline in TC and LDL-C in the F group (both P < 0.05) and in TC, LDL-C, and TGs in the OF group (P < 0.02, P < 0.02, and P < 0.05, respectively), as well as a significant increase in HDL-C in the OF group (P < 0.02). At 1 year, there were significant reduction from baseline in TC in the O, F, and OF groups (P < 0.05 and P < 0.01, respectively), LDL-C (P < 0.05, P < 0.02, and P < 0.01, respectively), and TGs (P < 0.02, P < 0.05, and P < 0.02, respectively). Also at 1 year, HDL-C was significantly higher than baseline in the F and OF groups (P < 0.02 and P < 0.01, respectively). CONCLUSION: Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments. [ABSTRACT FROM AUTHOR]
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- 2003
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78. Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.
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Derosa G, Mugellini A, Ciccarelli L, Crescenzi G, and Fogari R
- Abstract
BACKGROUND: Repaglinide and glimepiride are relatively new oral hypoglycemic agents. Few data are available concerning their effects on metabolic parameters other than measures of glycemic control. OBJECTIVES: In addition to assessing the effects of repaglinide and glimepiride on glycemic control in patients with type 2 diabetes mellitus, this study also examined the effects of these agents on 3 metabolic parameters known to be cardiovascular risk factors--lipoprotein(a) (Lp[a]), plasminogen activator inhibitor-1 (PAI-1), and homocysteine (Hcy). METHODS: This randomized, placebo-controlled, double-blind trial was conducted at a single center in Italy. Eligible patients were nonsmokers; had no hypertension or coronary heart disease; were taking no hypolipidemic drugs, diuretics, beta-blockers, or thyroxin; and had normal renal function. After an initial 4-week placebo washout period, patients were randomized to receive repaglinide 1 mg/d or glimepiride 1 mg/d. The dose of study drug was optimized over an 8-week titration period, which was followed by a 12-month treatment period. Measures of glycemic control (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPG], fasting plasma insulin [FPI], postprandial plasma insulin [PPI]) and the other metabolic parameters of interest were assessed after 6 and 12 months of treatment. RESULTS: One hundred twenty-four patients (63 women, 61 men) completed the study, 62 in each treatment group. There were no significant differences in demographic characteristics between groups. After 6 and 12 months of treatment, FPG levels and HbA1c values were significantly reduced from baseline in both groups (6 months, P < 0.05; 12 months, P < 0.01). After 6 months, PPG levels were significantly decreased only in the repaglinide group (P < 0.05 vs baseline); at 12 months, however, PPG levels were significantly reduced from baseline in both groups (P < 0.01 repaglinide, P < 0.05 glimepiride). No significant changes from baseline in FPI or PPI levels were seen in either group at 6 months, although FPI levels were significantly increased in the repaglinide group at 12 months (P < 0.05). Repaglinide significantly lowered levels of Lp(a), PAI-1, and Hcy after 12 months (all, P < 0.05 vs baseline). Glimepiride significantly lowered levels of Lp(a) and Hcy after 6 months (both, P < 0.05 vs baseline) and levels of Lp(a) (P < 0.01 vs baseline), Hcy (P < 0.01 vs baseline), and PAI-1 (P < 0.05 vs baseline) after 12 months. CONCLUSIONS: Repaglinide and glimepiride improved glycemic control and reduced levels of other metabolic parameters of interest in this population of patients with type 2 diabetes. It is possible that the reductions in Lp(a), PAI-1, and Hcy were the result of improved glucose metabolism; however, the possibility that repaglinide and glimepiride may have a direct effect on these parameters should not be excluded. [ABSTRACT FROM AUTHOR]
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- 2003
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79. Effects of fosinopril on blood pressure, lipid profile, and lipoprotein(a) levels in normotensive patients with type 2 diabetes and microalbuminuria: an open-label, uncontrolled study.
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Derosa G, Mugellini A, Ciccarelli L, Crescenzi G, and Fogari R
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Background: Patients with type 2 diabetes mellitus often have other cardiovascular risk factors, and alterations in lipid profile play an important role. The angiotensin-converting enzyme inhibitors are often used in these patients, particularly those with type 2 diabetes and proteinuria.Objective: This study evaluated the effects of fosinopril therapy on fasting plasma glucose (FPG), lipid profile, and lipoprotein(a), or Lp(a), levels in normotensive patients with type 2 diabetes mellitus and microalbuminuria.Methods: Normotensive (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] <85 mm Hg) patients with type 2 diabetes and microalbuminuria and a normal lipid profile were enrolled. Patients had their diabetes controlled by diet alone or diet plus oral hypoglycemic agents. Fosinopril 10 mg/d was administered for 6 months and then interrupted for 1 month. FPG, glycosylated hemoglobin, SBP, DBP, lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), Lp(a), albumin excretion rate (AER), and creatinine levels were evaluated at baseline; 1, 3, and 6 months after initiation of treatment; and 1 month after interruption of treatment.Results: A total of 120 patients were enrolled (63 men, 57 women; mean age +/- SD, 54 +/- 10 years; duration of diabetes, 7 +/- 2 years). Significant decreases versus baseline were observed in the following parameters at month 6: SBP (122 +/- 7 vs 117 +/- 9.1 mm Hg, P < 0.01), DBP (80 +/- 4.8 vs 74 +/- 4.5 mm Hg, P < 0.05), TC (186 +/- 11 vs 176 +/- 10 mg/dL, P < 0.05), LDL-C (124 +/- 10 vs 114 +/- 11 mg/dL, P < 0.05), Lp(a) (24 +/- 10 vs 19 +/- 7.5 mg/dL, P < 0.05), and AER (103 +/- 45 vs 48 +/- 21 mg/24 hours, P < 0.01). When fosinopril therapy was interrupted for 1 month, the values for all these parameters tended to return to baseline values; SBP, TC, and Lp(a) values were significantly different from month 6 values, whereas DBP, LDL-C, and AER did not change significantly during the washout period.Conclusions: Fosinopril therapy for 6 months resulted in a reduction of microalbuminuria and an improvement in lipid profile and Lp(a) levels in patients with type 2 diabetes. This suggests that fosinopril may improve lipid profile and reduce Lp(a) levels by lowering proteinuria or by other more direct actions on lipid and Lp(a) metabolism. Additional controlled studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]
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- 2002
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80. Additive Manufactured Scaffolds for Bone Tissue Engineering: Physical Characterization of Thermoplastic Composites with Functional Fillers
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Michele Sisani, Lucia Ciccarelli, Ambra Gambardella, Andrea Roberto Calore, Jules Harings, Maria Cámara-Torres, Iñigo Calderon Uriszar-Aldaca, Marco Scatto, Lorenzo Moroni, Alberto Sanchez, Veronica Vanzanella, Ravi Sinha, Nino Grizzuti, Sara Villanueva, Amaia Matanza, Sergio de la Fuente Perez, Rune Wendelbo, Carlos Mota, Alessandro Patelli, European Commission, Sinha, R., Sanchez, A., Camara-Torres, M., Uriszar-Aldaca, I. C., Calore, A. R., Harings, J., Gambardella, A., Ciccarelli, L., Vanzanella, V., Sisani, M., Scatto, M., Wendelbo, R., Perez, S., Villanueva, S., Matanza, A., Patelli, A., Grizzuti, N., Mota, C., Moroni, L., RS: MERLN - Complex Tissue Regeneration (CTR), and CTR
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Thermoplastic ,Materials science ,COPOLYMER SCAFFOLDS ,Polymers and Plastics ,Additive manufacturing ,additive manufacturing ,composites ,fillers ,mechanical properties ,modeling ,rheology ,Composite number ,Mechanical properties ,02 engineering and technology ,engineering.material ,010402 general chemistry ,01 natural sciences ,Article ,chemistry.chemical_compound ,Rheology ,Filler (materials) ,mechanical propertie ,composite ,Composite material ,Bone regeneration ,Elastic modulus ,Composites ,chemistry.chemical_classification ,Process Chemistry and Technology ,Organic Chemistry ,filler ,Modeling ,Polymer ,MECHANICAL-PROPERTIES ,DEGRADATION ,021001 nanoscience & nanotechnology ,Fillers ,0104 chemical sciences ,chemistry ,Zirconium phosphate ,engineering ,GRAPHENE OXIDE ,MORPHOLOGY ,Extrusion ,CRYSTALLIZATION ,0210 nano-technology ,CARTILAGE REPAIR - Abstract
Thermoplastic polymer–filler composites are excellent materials for bone tissue engineering (TE) scaffolds, combining the functionality of fillers with suitable load-bearing ability, biodegradability, and additive manufacturing (AM) compatibility of the polymer. Two key determinants of their utility are their rheological behavior in the molten state, determining AM processability and their mechanical load-bearing properties. We report here the characterization of both these physical properties for four bone TE relevant composite formulations with poly(ethylene oxide terephthalate)/poly(butylene terephthalate (PEOT/PBT) as a base polymer, which is often used to fabricate TE scaffolds. The fillers used were reduced graphene oxide (rGO), hydroxyapatite (HA), gentamicin intercalated in zirconium phosphate (ZrP-GTM) and ciprofloxacin intercalated in MgAl layered double hydroxide (MgAl-CFX). The rheological assessment showed that generally the viscous behavior dominated the elastic behavior (G″ > G′) for the studied composites, at empirically determined extrusion temperatures. Coupled rheological–thermal characterization of ZrP-GTM and HA composites showed that the fillers increased the solidification temperatures of the polymer melts during cooling. Both these findings have implications for the required extrusion temperatures and bonding between layers. Mechanical tests showed that the fillers generally not only made the polymer stiffer but more brittle in proportion to the filler fractions. Furthermore, the elastic moduli of scaffolds did not directly correlate with the corresponding bulk material properties, implying composite-specific AM processing effects on the mechanical properties. Finally, we show computational models to predict multimaterial scaffold elastic moduli using measured single material scaffold and bulk moduli. The reported characterizations are essential for assessing the AM processability and ultimately the suitability of the manufactured scaffolds for the envisioned bone regeneration application., The work was supported by a Horizon 2020 Research and Innovation Programme grant from the European Union, called the FAST project (grant no. 685825, project website: http://project-fast.eu). The authors acknowledge the support of the FAST project consortium for the various aspects of this work.
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- 2021
81. Effects of 1 year of treatment with pioglitazone or rosiglitazone added to glimepiride on lipoprotein (a) and homocysteine concentrations in patients with type 2 diabetes mellitus and metabolic syndrome: a multicenter, randomized, double-blind, controlled clinical trial [corrected] [published erratum appears in CLIN THER 2006 Sep;28(9):1483].
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Derosa G, Cicero AFG, D'Angelo A, Gaddi A, Ciccarelli L, Piccinni MN, Salvadeo SAT, Pricolo F, Ferrari I, Gravina A, and Ragonesi PD
- Abstract
BACKGROUND: Although the metabolic effects of the thiazolidinediones have been well studied, there is a lack of comparative data on their effects on certain cardiovascular risk factors, such as elevated plasma levels of lipoprotein (a) (Lp[a]) and homocysteine (Hcy). OBJECTIVE: This study compared the effects of pioglitazone or rosiglitazone added to glimepiride on a range of lipid parameters, focusing on Lp(a) and Hcy, in patients with type 2 diabetes mellitus and the metabolic syndrome. METHODS: This was a multicenter, randomized, controlled, double-blind study in patients with type 2 diabetes and the metabolic syndrome (hypertension [>or=130/85 mm Hg]) and triglyceridemia (>or=150 mg/dL). In addition to glimepiride 4 mg/d, patients received pioglitazone 15 mg QD or rosiglitazone 4 mg QD for 1 year. The primary efficacy variables were change from baseline in body mass index (BMI), glycosylated hemoglobin (HbA(1c)), Lp(a), and Hey. Secondary efficacy measures were changes in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) concentrations, fasting and postprandial insulin concentrations (FPI and PPI, respectively), the Homeostasis Model Assessment index, and the lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides). All these parameters were measured after a 12-hour fast every 3 months for 1 year. Tolerability was assessed based on reported adverse events and laboratory abnormalities at each study visit. RESULTS: Ninety-one white patients with type 2 diabetes and the metabolic syndrome were enrolled, and 87 completed the study (43 men, 44 women; mean [SD] age, 53 [6] years; mean weight, 68.4 [3.3] kg). Mean baseline values for BMI and HbA(1c) were 24.3 (0.8) kg/m(2) and 8.1% (0.8%), respectively. At the end of 1 year, both treatment groups had significant increases from baseline in BMI (4.9% glimepiride + pio glitazone, 6.2% glimepiride + rosiglitazone; P < 0.05). Glimepiride + pioglitazone was associated with the following percent improvements from baseline in measures of glycemic control: -17.1% in HbA(1c), -19.3% in FPG, -17.8% in PPG, -40.1% in FPI, and -22.6% in PPI (all, P < 0.01). The corresponding percent improvements from baseline with glimepiride + rosiglitazone were -16.3%, -19.9%, -15.0%, -44.8%, and -22.1% (all, P < 0.01). There were no significant differences between treatment groups in any of these parameters. The pioglitazone group had significant improvements from baseline in TC (-11.1%), LDL-C (-12.0%), HDL-C (15.0%), and triglycerides (-22.4%) [corrected] (all, P < 0.05), whereas the rosiglitazone group had significant increases in TC (14.9%), LDL-C (16.5%), and triglycerides (17.9%) (all, P < 0.05); the difference between pioglitazone and rosiglitazone was statistically significant (P < 0.05). The change from baseline in Lp(a) was significant in the pioglitazone group, both relative to baseline and compared with the rosiglitazone group (-19.7% vs 0.5%, respectively; P < 0.05 vs baseline and vs rosiglitazone). Changes from baseline in Hey were significant in both the pioglitazone and rosiglitazone groups (-20.2% and -25.0%, respectively; P < 0.05), with no significant difference between groups. Both treatments were well tolerated, and no patients had significant changes in transaminases. CONCLUSIONS: In these patients with type 2 diabetes and the metabolic syndrome, the combinations of glimepiride with pioglitazone and glimepiride with rosiglitazone produced significant improvements in measures of glycemic control, plasma lipids, and homocysteinemia. One year of treatment with the pioglitazone combination was associated with significantly reduced plasma Lp(a) levels compared with the rosiglitazone combination. [ABSTRACT FROM AUTHOR]
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- 2006
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82. Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial.
- Author
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Derosa G, Cicero AFG, Bertone G, Piccinni MN, Ciccarelli L, and Roggeri DP
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BACKGROUND: Diabetes risk is often complicated by a mixed hyperlipoproteinemia not sufficiently controlled by a single antihyperlipidemic drug; however, there are some concerns about the safety of combined statin and fibrate treatments. OBJECTIVE: The aim of this study was to compare the efficacy and safety profile of fluvastatin + fenofibrate combination therapy and those of fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus (DM), and coronary heart disease (CHD) (ie, high risk for cardiovascular disease [CVD]). METHODS: This 12-month, randomized, double-blind, controlled trial was conducted at the University of Pavia, Pavia, Italy. Patients aged 18 to 80 years with combined hyperlipidemia, type 2 DM, and CHD were randomly assigned to receive combination therapy with extended-release fluvastatin 80 mg + micronized fenofibrate 200 mg or monotherapy with extended-release fluvastatin 80 mg. All treatments were given in tablet form, once daily with the evening meal, for 12 months. Lipid variables (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) at 6 and 12 months were the primary efficacy variables, and glycemic status (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose, and postprandial plasma glucose levels) at 6 and 12 months was the secondary efficacy variable. Tolerability was assessed using physical examination, including vital-sign assessment, body-weight measurement, electrocardiography, adverse events, and laboratory tests. A pharmacoeconomic analysis of both treatment regimens was also carried out using the incremental cost-effectiveness ratio (ICER). RESULTS: A total of 48 patients (24 men, 24 women; mean [SD] age, 60 [5] years) were enrolled. After 6 months, all primary efficacy variables, except for TG level, showed significant improvements from baseline only in the combination-therapy group (changes: LDL-C, -25%; HDL-C, +12%; and TC, -19%; all, P < 0.05 vs baseline). After 12 months, lipid variables showed significant improvements over baseline in both groups (all, P < 0.05), except for TG in the monotherapy group. Significant changes in LDL-C, HDL-C, and TG were found in the combination-therapy group (-35%, +34%, -32%, respectively) versus the monotherapy group (-25%, +14%, -17%, respectively; all, P < 0.05 between groups). The change from baseline in HbA(1c) level was significant with combination therapy (-12% vs -7%; P < 0.05). Both treatments were well tolerated, with no significant differences in the incidences of adverse events between the 2 groups. The ICER showed that each 1% decrease in LDL-C level achieved with the fenofibrate + fluvastatin combination added a cost of 14.97 Euros/y (US 12.25 US dollars/y), and each 1% increase in HDL-C level added a cost of 7.48 Euros/y (6.12/y US dollars), over the cost of monotherapy. CONCLUSIONS: In this selected sample of patients with combined hyperlipidemia, type 2 DM, and CHD, the combination of extended-release fluvastatin + micronized fenofibrate was associated with a more improved lipid profile than fluvastatin monotherapy, and was a well-tolerated and cost-effective therapeutic choice to treat these patients at high risk for CVD. [ABSTRACT FROM AUTHOR]
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- 2004
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83. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized, double-blind study.
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Derosa G, Cicero AFG, Bertone G, Piccinni MN, Fogari E, Ciccarelli L, and Fogari R
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BACKGROUND: Angiotensin receptor blockers (ARBs) provide effective blood pressure control. Whereas none of the ARBs appear to affect glucose homeostasis, some ARBs have been associated with a decrease in cholesterolemia. OBJECTIVE: This study was conducted to evaluate blood pressure control glucose homeostasis, and the plasma lipid profile in patients with type 2 diabetes mellitus and mild hypertension during 12 months of treatment with the ARB telmisartan or nifedipine gastrointestinal therapeutic system (GITS). METHODS: In this double-blind trial, patients taking oral hypoglycemic agents were randomized to receive telmisartan 40 mg or nifedipine GITS 20 mg once daily for 12 months. At the time of enrollment, patients were given advice on diet (1400-1600 kcal/d) and exercise (stationary bicycle for > or =30 min, 4 d/wk). Assessments of systolic blood pressure (SBP), diastolic blood pressure, body mass index (BMI), fasting plasma glucose concentrations, glycosylated hemoglobin, fasting plasma insulin concentrations, the homeostasis model assessment of insulin resistance, and the lipid profile were performed at baseline and after 6 and 12 months of treatment. RESULTS: One hundred sixteen patients were divided into 2 age- and sex-matched treatment groups (58 men, 58 women; mean [SD] age, 52.5 [5] years). All patients were in good general health at baseline; had achieved adequate glycemic control with diet and oral hypoglycemic agents; were taking antihypercholesterolemic drugs; and had no evidence of macroangiopathy, microalbuminuria, or neuropathy. There were significant reductions from baseline in seated trough SBP after 12 months of treatment with both telmisartan and nifedipine GITS (from 139 [4] to 132 [4] mm Hg and from 140 [4] to 130 [4] mm Hg, respectively; both, P < 0.01). No change in BMI or glucose metabolism was observed with either treatment. After 12 months, there were significant improvements in concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) with telmisartan (-9% and -11.5%, respectively; both, P < 0.01) compared with nifedipine GITS (-2% and -1.5%). CONCLUSIONS: In this selected sample of patients with type 2 diabetes and mild hypertension, both telmisartan and nifedipine GITS produced significant reductions in blood pressure. Telmisartan was associated with a slight but statistically significant improvement in plasma TC and LDL-C concentrations compared with nifedipine GITS. [ABSTRACT FROM AUTHOR]
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- 2004
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84. Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with glimepiride: a twelve-month, multicenter, double-blind, randomized, controlled, parallel-group trial.
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Derosa G, Cicero AFG, Gaddi A, Ragonesi PD, Fogari E, Bertone G, Ciccarelli L, and Piccinni MN
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BACKGROUND: Glimepiride is approved as monotherapy and in combination with metformin or with insulin, whereas the combination of glimepiride with other antihyperglycemic drugs is under investigation. OBJECTIVE: The aim of this study was to assess the differential effect on glucose and lipid variables and tolerability of the combination of glimepiride plus pioglitazone or rosiglitazone in patients with type 2 diabetes mellitus (DM) and metabolic syndrome. METHODS: This 12-month, multicenter, double-blind, randomized, controlled, parallel-group trial was conducted at 3 study sites in Italy. We assessed patients with type 2 DM (duration, > or =6 months) and with metabolic syndrome. All patients were required to have poor glycemic control with, or to have experienced > or =1 adverse effect (AE) with, diet and oral hypoglycemic agents such as sulfonylureas or metformin, both given up to the maximum tolerated dose. All patients received a fixed oral dose of glimepiride, 4 mg/d divided into 2 doses, self-administered for 12 months. Patients also were randomized to receive oral pioglitazone (15 mg once daily) (G + P group) or oral rosiglitazone (4 mg once daily) (G + R group), self-administered for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA(1c)], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI, and PPI, respectively], and homeostasis model assessment index), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and lipoprotein variables (apolipoprotein [apo] A-I and apo B) at baseline and at 3, 6, 9, and 12 months of treatment. Treatment tolerability was assessed at each study visit using a thorough interview of patients, and comparisons of clinical and laboratory values to baseline levels. RESULTS: A total of 91 patients were enrolled in the study; 87 patients completed it (G + P group: 24 women, 21 men; mean [SD] age, 53 [6] years; G + R group: 20 women, 22 men; mean [SD] age, 54 [5] years). Patients in the G + P and G + R groups experienced significant increases in mean BMI at 12 months compared with baseline (4.92% and 6.17%, respectively; both, P < 0.05). The combination of glimepiride with pioglitazone or rosiglitazone significantly improved glycemic control in the study patients. At 12 months, we observed a 1.3% improvement in mean values for plasma HbA(1c) concentration (P < 0.01) 19.3% in FPG (P < 0.01), 16.3% in PPG (P < 0.01), 42.4% in FPI ), and 23.3% in PPI (P <0.05); no significant differences were found between treatment groups. Although the G + P group experienced a significant improvement at 12 months in almost all variables of lipid metabolism from baseline (TC, - 11%; LDL-C, -12%; HDL-C, 15%; and apo B, - 10.6% [all, P , 0.05]), the G + R group experienced a significant increase in mostly the lipid risk factors for cardiovascular disease (TC, 14.9%; LDL-C, 16.5%; TG, 17.9%; and apo B, 10.3% [all, P , 0.05]). Overall, no statistically significant changes in plasma aminotransferase activities were observed. Of the 87 patients who completed the study, 6.7% (3/45) of patients in the G + P group and 11.9% (5/42) of patients in the G + R group had transient, mild to moderate AEs that did not cause withdrawal from the trial. CONCLUSION: In this study of patients with type 2 DM and metabolic syndrome who did not respond adequately to, or experienced AEs with, diet and either a sulfonylurea or metformin previously, the combination of glimepiride plus pioglitazone was associated with a significant improvement in lipid and lipoprotein variables, whereas the combination of glimepiride plus rosiglitazone appears to not have had any clinically significant effect on lipid metabolism. [ABSTRACT FROM AUTHOR]
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- 2004
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85. The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus.
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Derosa G, Cicero AFG, Gaddi A, Mugellini A, Ciccarelli L, and Fogari R
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BACKGROUND: A previous study has demonstrated that L-carnitine reduces plasma lipoprotein(a) (Lp[a]) levels in patients with hypercholesterolemia. OBJECTIVE: To test a tolerable Lp(a)-reducing agent in diabetic patients, we assessed the effect of a dietary supplementation of L-carnitine on plasma lipid levels, particularly Lp(a), of patients with type 2 diabetes mellitus (DM) and hypercholesterolemia. METHODS: In this 6-month, randomized, double-masked, placebo-controlled clinical trial, patients were enrolled, assessed, and followed up at the Diabetic and Metabolic Diseases Center of the Department of Internal Medicine and Therapeutics at the University of Pavia, Pavia, Italy. All study patients had newly diagnosed type 2 DM that was managed through dietary restriction alone throughout the study, as well as hypercholesterolemia. Patients were randomized to 1 of 2 groups. One group received L-carnitine, one 1-g tablet BID. The other group received a corresponding placebo. We assessed body mass index, fasting plasma glucose, postprandial plasma glucose, glycosylated hemoglobin, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B, and Lp(a) at baseline and at 1, 3, and 6 months of treatment. RESULTS: This study included 94 patients. The treatment group included 24 men and 22 women (mean [SD] age, 52 [6] years). The placebo group included 23 men and 25 women (mean [SD] age, 50 [7] years). The baseline characteristics of the groups did not differ significantly. The mean (SD) body weight, height, and body mass index were 78.2 (5.8) kg, 1.70 (0.04) m, and 27.3 (2.5) kg/m(2), respectively, in the L-carnitine group and 77.6 (6.4) kg, 1.71 (0.05) m, and 26.8 (2.2) kg/m(2), respectively, in the placebo group. In the treatment group, Lp(a) was significantly reduced at 3 and 6 months compared with baseline (P < 0.05) and P < 0.01, respectively). We observed a significant improvement after 6 months (P < 0.05) in the Lp(a) value in patients taking L-carnitine compared with those taking placebo. Between-group differences in other variables did not reach a level of significance at months 3 and 6. No drug-related adverse events were reported or observed. CONCLUSION: In this preliminary study, after 3 and 6 months, L-carnitine significantly lowered the plasma Lp(a) level compared with placebo in selected hypercholesterolemic patients with newly diagnosed type 2 DM. [ABSTRACT FROM AUTHOR]
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- 2003
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86. Differences in the perception and time course of syntactic and semantic violations.
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De Vincenzi M, Job R, Di Matteo R, Angrilli A, Penolazzi B, Ciccarelli L, Vespignani F, De Vincenzi, Marica, Job, Remo, Di Matteo, Rosalia, Angrilli, Alessandro, Penolazzi, Barbara, Ciccarelli, Laura, and Vespignani, Francesco
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A reading time and an ERP experiment conducted in Italian investigated the parser's responses to a syntactic violation (subject-verb number agreement) and to a semantic violation (subject-verb selectional restriction), examining the time course of comprehension processes until sentence end. The reading-time data showed that the syntactic violation was detected earlier than the semantic one and that the two violations differed in the time-course. The ERP data fully supported the reading time data: Syntactic anomalies elicited a left anterior negativity (LAN) and a P600. Semantic anomalies elicited a N400 centred on the parietal sites which started 90 ms later (latency 430 ms) than the LAN. Furthermore, the N400 evoked by the words that followed the target word continued and increased until sentence end. The results are discussed with respect to the hypotheses that the parser constructs distinct syntactic and semantic analyses of a sentence and that this characteristic holds cross-linguistically. The appropriateness of different methodologies to the study of sentence processing is also evaluated. [ABSTRACT FROM AUTHOR]
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- 2003
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87. Human CHN1 Mutations Hyperactivate α2-Chimaerin and Cause Duane's Retraction Syndrome
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Susan Lindsay, Sarah Guthrie, Binoy Appukuttan, Long Cheng, Michelle Cheung, Elizabeth R. Young, J. Timothy Stout, Alfonso Baldi, Dominic Davenport, Noriko Miyake, Jim Allen, Moira Crosier, Maria Laura Ciccarelli, Mustafa Sahin, Mara Campioni, Wai-Man Chan, Maria Psatha, Alessandro Iannaccone, Stephen P. Christiansen, Nick J. Gutowski, Caroline Andrews, John K. Chilton, Elizabeth C. Engle, Laura E. Mariani, Sian Ellard, Juan Carlos Zenteno, Krystal Law, Miyake, N., Chilton, J., Psatha, M., Cheng, L., Andrews, C., Chan, W., Law, K., Crosier, M., Lindsay, M., Cheung, M., Allen, J., Gutowsky, N., Ellard, S., Young, E., Iannaccone, A., Appukuttan, B., Stout, J., Christiansen, S., Ciccarelli, L., Baldi, Alfonso, Campioni, M., Zenteno, J., Mariani, L., Sahin, M., Guthrie, S., and Engle, E.
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Male ,Heterozygote ,Duane’s retraction syndrome ,Molecular Sequence Data ,Nonsense mutation ,Mutant ,Mutation, Missense ,Chick Embryo ,Extraocular muscles ,Duane Retraction Syndrome ,Article ,Cell Line ,Abducens Nerve ,Oculomotor Nerve ,Chimerin 1 ,medicine ,Animals ,Humans ,Missense mutation ,Amino Acid Sequence ,Genetics ,Multidisciplinary ,biology ,Gene Expression Profiling ,Cell Membrane ,Axons ,eye diseases ,Pedigree ,Cell biology ,Oculomotor Muscle ,medicine.anatomical_structure ,Oculomotor Muscles ,biology.protein ,RacGAP signaling protein ,Female ,Axon guidance - Abstract
Duane's retraction syndrome (DRS) is a complex congenital eye movement disorder caused by aberrant innervation of the extraocular muscles by axons of brainstem motor neurons. Studying families with a variant form of the disorder (DURS2-DRS), we have identified causative heterozygous missense mutations in CHN1 , a gene on chromosome 2q31 that encodes α2-chimaerin, a Rac guanosine triphosphatase–activating protein (RacGAP) signaling protein previously implicated in the pathfinding of corticospinal axons in mice. We found that these are gain-of-function mutations that increase α2-chimaerin RacGAP activity in vitro. Several of the mutations appeared to enhance α2-chimaerin translocation to the cell membrane or enhance its ability to self-associate. Expression of mutant α2-chimaerin constructs in chick embryos resulted in failure of oculomotor axons to innervate their target extraocular muscles. We conclude that α2-chimaerin has a critical developmental function in ocular motor axon pathfinding.
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- 2008
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88. Matrix Metalloproteinase-2, -9, and Tissue Inhibitor of Metalloproteinase-1 in Patients with Hypertension
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Sibilla A T Salvadeo, Fabio Pricolo, Carmine Tinelli, Arrigo F G Cicero, Mario N. Piccinni, Alessia Gravina, Simona Galli, Leonardina Ciccarelli, Giuseppe Derosa, Lorenza Montagna, Ilaria Ferrari, S. Paniga, Angela D'Angelo, Derosa G., D'Angelo A., Ciccarelli L., Piccinni M.N., Pricolo F., Salvadeo S., Montagna L., Gravina A., Ferrari I., Galli S., Paniga S., Tinelli C., and Cicero A
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Inflammation ,Matrix metalloproteinase ,Extracellular matrix ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Fibrinolysis ,medicine ,Humans ,In patient ,Metalloproteinase ,Tissue Inhibitor of Metalloproteinase-1 ,business.industry ,Case-control study ,Blood Pressure Determination ,Cell Biology ,General Medicine ,Metabolism ,Middle Aged ,Tissue inhibitor of metalloproteinase ,Lipids ,Endocrinology ,Matrix Metalloproteinase 9 ,Case-Control Studies ,Hypertension ,Matrix Metalloproteinase 2 ,Female ,medicine.symptom ,business - Abstract
There are conflicting data in the literature regarding the expression pattern of the vascular matrix metalloproteinase (MMP) system and their inhibitors (TIMPs) in human hypertension. The authors hypothesized that MMP-2, MMP-9, and TIMP-1 would be abnormal in hypertension, reflecting alterations in extracellular matrix (ECM) turnover. The authors measured plasma levels and activities of MMP-2, MMP-9, and TIMP-1 in 44 hypertensive patients and 44 controls. MMP-2 levels and activity were significantly higher in hypertensive group (p < .0001). Significant increase was also observed for MMP-9 level and activity (p < .0001) and for TIMP-1 (p < .0001) in hypertensive patients. Plasma levels and activities of MMP-2, MMP-9, and TIMP-1 are increased in hypertensive patients, which may reflect abnormal ECM metabolism.
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- 2006
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89. Matrix Metalloproteinase-2, -9 and Tissue Inhibitor Metalloproteinase-1 in Patients with Hypertension Before and After Doxazosin Therapy
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Roberto Fogari, Carmine Tinelli, Simona Galli, Sibilla A T Salvadeo, Alessia Gravina, Angela D'Angelo, Ilaria Ferrari, Arrigo F G Cicero, S. Paniga, Fabio Pricolo, Leonardina Ciccarelli, Lorenza Montagna, Giuseppe Derosa, Elena Fogari, Mario N. Piccinni, Derosa G., Cicero A., D’Angelo A., Tinelli C., Ciccarelli L., Piccinni M.N., Pricolo F., Salvadeo F., Montagna L., Fogari E., Gravina A., Ferrari I., Galli S., Paniga S., and Fogari R.
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medicine.medical_specialty ,Metalloproteinase ,business.industry ,Doxazosin ,Matrix metalloproteinase ,Pharmacology ,Extracellular matrix ,Pharmacotherapy ,Endocrinology ,Felodipine ,Expression pattern ,Internal medicine ,Hypertension ,Internal Medicine ,medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background: There are conflicting data in the literature regarding both the expression pattern of the vascular metalloproteinase (MMP) system and its tissue inhibitors (TIMPs) in human hypertension and the effect of antihypertensive drugs in modifying the MMP/TIMP system. This study was designed to test the hypothesis that MMP-2, MMP-9 and TIMP-1 are altered in hypertension reflecting alterations in extracellular matrix turnover. Moreover, the aim of the study was to assess whether chronic antihypertensive treatment with doxazosin would normalise these alterations. Materials and results: We measured plasma levels and activities of MMP-2, MMP-9 and TIMP-1 in 44 hypertensive patients before and after 4 months of doxazosin treatment. MMP-2 levels and activity were significantly lower in the hypertensive group after treatment (p < 0.0001) compared with respective values before treatment. Significant decrease was also observed for MMP-9 level and activity (p < 0.0001) and for TIMP-1 (p < 0.0001) in hypertensive patients after antihypertensive treatment. Conclusions: Plasma levels and activities of MMP-2, MMP-9 and TIMP-1 are decreased in hypertensive patients after treatment compared with respective values before treatment. This may demonstrate that antihypertensive drugs modify the MMP/TIMP system, contributing to the mechanisms of vascular remodelling.
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- 2006
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90. Antithrombotic Effects of Rosiglitazone-Metformin versus Glimepiride-Metformin Combination Therapy in Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome
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M. Ghelfi, Sibilla A T Salvadeo, Leonardina Ciccarelli, Emmanouil Peros, Arrigo F G Cicero, Antonio Vittorino Gaddi, Mario N. Piccinni, Giuseppe Derosa, Ilaria Ferrari, Derosa G, Gaddi AV, Piccinni MN, Ciccarelli L, Salvadeo S, Peros E, Ghelfi M, Ferrari I, and Cicero AF.
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Blood Glucose ,Male ,medicine.medical_specialty ,Type 2 diabetes ,Gastroenterology ,Rosiglitazone ,Insulin resistance ,Double-Blind Method ,Fibrinolytic Agents ,Internal medicine ,Diabetes mellitus ,Plasminogen Activator Inhibitor 1 ,medicine ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,Glycated Hemoglobin ,Metabolic Syndrome ,business.industry ,Fibrinogen ,Middle Aged ,medicine.disease ,Metformin ,Glimepiride ,Sulfonylurea Compounds ,Endocrinology ,Postprandial ,Diabetes Mellitus, Type 2 ,Tissue Plasminogen Activator ,Drug Therapy, Combination ,Female ,Thiazolidinediones ,Metabolic syndrome ,business ,medicine.drug - Abstract
Study Objective. To evaluate the differential effect on coagulation and fibrinolysis parameters of combination therapy with glimepiride-metformin and with rosiglitazone-metformin beyond their effect on glucose metabolism in patients with type 2 diabetes and metabolic syndrome. Design. Multicenter, double-blind, randomized, controlled trial. Setting. Two university-affiliated medical centers in Italy. Patients. Ninety-five patients with type 2 diabetes for at least 6 months without glycemic control by diet and oral hypoglycemic agents to their maximum tolerated dosage and who also had metabolic syndrome. Intervention. All 95 patients received metformin 1500 mg/day In a randomized manner, 47 patients received glimepiride 2 mg/day and 48 patients received rosiglitazone 4 mg/day. Measurements and Main Results. Body mass index (BMI), glycemic control, and coagulation and fibrinolysis parameters were evaluated at 3, 6, 9, and 12 months of treatment. Compared with baseline values, significant decreases in BMI, fasting plasma glucose, postprandial plasma glucose, and hemoglobin A1c were observed at 12 months in both the glimepiride and rosiglitazone groups (p
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- 2005
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91. Effects of exenatide and metformin in combination on some adipocytokine levels: a comparison with metformin monotherapy
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Fabrizio Querci, Giuseppe Derosa, Anna Carbone, Arrigo F G Cicero, Leonardina Ciccarelli, Pamela Maffioli, Angela D'Angelo, Elena Fogari, Ivano Franzetti, Derosa G, Cicero AF, Franzetti IG, Querci F, Carbone A, Ciccarelli L, D'Angelo A, Fogari E, and Maffioli P.
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Blood Glucose ,Male ,Time Factors ,endocrine system diseases ,Physiology ,Pharmacology ,law.invention ,Body Mass Index ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Insulin-Secreting Cells ,Insulin ,C-peptide ,General Medicine ,Middle Aged ,Lipids ,Metformin ,Intention to Treat Analysis ,Treatment Outcome ,Italy ,Drug Therapy, Combination ,Female ,Inflammation Mediators ,medicine.drug ,medicine.medical_specialty ,Adipokine ,Drug Administration Schedule ,Insulin resistance ,Adipokines ,Double-Blind Method ,Physiology (medical) ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Analysis of Variance ,Intention-to-treat analysis ,Chi-Square Distribution ,business.industry ,Venoms ,nutritional and metabolic diseases ,medicine.disease ,Endocrinology ,chemistry ,Diabetes Mellitus, Type 2 ,Exenatide ,Insulin Resistance ,business ,Peptides ,Biomarkers - Abstract
The aim of this study was to evaluate the effects of exenatide on levels of serum adipocytokines and on β-cell function. The study was conducted between 2008 and 2012. After a run-in period with metformin, 174 patients with type-2 diabetes were randomly distributed to either a group receiving exenatide at 10 μg twice daily, or a group receiving the placebo, for 12 months. We evaluated body mass index (BMI), blood pressure, glycemic control, lipid profile, fasting plasma insulin (FPI), HOMA-IR, HOMA-β, fasting plasma proinsulin (FPPr), proinsulin : fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, retinol binding protein-4 (RBP-4), visfatin, omentin-1, and microalbuminuria. We used ELISA methods to assess the various parameters. Patients also underwent a combined euglycemic-hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation. After 12 months, a combination of exenatide and metformin produced a better decrease in body mass, BMI, glycemic control, FPI, FPPr, FPPr/FPI ratio, HOMA-IR, and glucagon level. Treatment with exenatide + metformin was superior to the placebo + metformin in increasing HOMA-β, C-peptide, and β-cell function. Significant negative correlations were found between M value, an index of insulin sensitivity, and measured adipocytokines. In conclusion, the combination of exenatide + metformin plays a role in improving some adipocytokine levels, and is better than metformin alone. The significant negative correlation between M value and measured adipocytokines is another confirmation of the positive effects linked to the improvement in insulin sensitivity.
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- 2013
92. Structural and dynamic properties of incomplete immunoglobulin-like fold domains
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Alfonso De Simone, Rita Berisio, Luciano Ciccarelli, Flavia Squeglia, Luigi Vitagliano, Berisio, R., Ciccarelli, L., Squeglia, F., De Simone, A., and Vitagliano, L.
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Models, Molecular ,Molecular dynamic ,Protein Folding ,Gram-negative bacteria ,Molecular Sequence Data ,Immunoglobulins ,MSCRAMM ,Immunoglobulin domain ,Antiparallel (biochemistry) ,Biochemistry ,Structural Biology ,Animals ,Humans ,Amino Acid Sequence ,Structural motif ,Cell adhesion ,biology ,Sequence Homology, Amino Acid ,Kinase ,Pili ,General Medicine ,adhesins ,biology.organism_classification ,molecular dynamics ,Cell biology ,Protein Structure, Tertiary ,Bacterial adhesin ,Crystallography ,biology.protein ,Immunoglobulin fold ,Antibody ,Adhesin - Abstract
The immunoglobulin fold (Ig-fold) is a widespread structural motif that is detected in a variety of proteins involved in diversified biological processes. The Ig-fold contains 70-110 residues that are assembled in a characteristic sandwich-like structure formed by two facing β-sheets each made of antiparallel β-strands. A number of variations on this common theme have been detected and described (Ig-like fold). One of the most intriguing variants is characterized by the lack of a strand compared to the canonical motif (incomplete Ig-like fold). Interestingly, proteins exhibiting incomplete Ig-like fold have been shown to play an important role in mediating either protein-protein or domain-domain interactions. Protein-protein interactions mediated by incomplete Ig-like folds play a key structural role in the chaperone-usher pathway, a process that generates multi-protein assemblies essential for the adhesion of gram negative bacteria. Domains with incomplete Ig-like fold have also been discovered in the mechanism of action of adhesins belonging to the family of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules). Recently, a stable incomplete Iglike fold has been detected in the peptidoglycan-binding extra-cellular portion of Staphylococcus aureus PrkC, an important Ser/Thr membrane kinase involved in bacterial growth and revival from latency. It is important to note that the occurrence of proteins with incomplete Ig-like fold is often related to cell adhesion and infectivity of bacterial pathological agents. We here report a survey of the structural data available on this peculiar structural motif highlighting analogies and differences of incomplete Ig-like fold involved in different processes. The dynamical behavior of these domains, investigated by molecular dynamics techniques, will be also commented. © 2012 Bentham Science Publishers.
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- 2011
93. Exenatide versus glibenclamide in patients with diabetes
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G Gadaleta, M. N. Piccinni, Giuseppe Derosa, Pamela Maffioli, Ilaria Ferrari, P. D. Ragonesi, Fabrizio Querci, S. A. T. Salvadeo, Ivano Franzetti, Arrigo F G Cicero, Leonardina Ciccarelli, Angela D'Angelo, Derosa G., Maffioli P., Salvadeo S.A., Ferrari I., Ragonesi P.D., Querci F., Franzetti I.G., Gadaleta G, Ciccarelli L., Piccinni M.N., D'Angelo A., and Cicero A.F.G
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Blood Glucose ,Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Body Mass Index ,Glibenclamide ,chemistry.chemical_compound ,Endocrinology ,Diabetes mellitus ,Insulin-Secreting Cells ,Glyburide ,Resistin ,Aged, 80 and over ,Middle Aged ,Metformin ,Medical Laboratory Technology ,C-Reactive Protein ,Female ,Retinol binding ,medicine.drug ,Proinsulin ,Adult ,medicine.medical_specialty ,Adolescent ,Incretins ,Young Adult ,Insulin resistance ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Aged ,Glycated Hemoglobin ,business.industry ,Venoms ,Body Weight ,Type 2 Diabetes Mellitus ,nutritional and metabolic diseases ,medicine.disease ,chemistry ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Exenatide ,Glycated hemoglobin ,Insulin Resistance ,business ,Peptides ,Retinol-Binding Proteins, Plasma - Abstract
BACKGROUND: Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes. METHODS: One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months. RESULTS: Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide. CONCLUSIONS: Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and beta-cell function, giving also a decrease of body weight and of inflammatory state.
- Published
- 2010
94. Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha
- Author
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Sibilla A T Salvadeo, Roberto Fogari, Leonardina Ciccarelli, Pietro D. Ragonesi, Mario N. Piccinni, Giuseppe Derosa, Arrigo F G Cicero, Alessia Gravina, Fabio Pricolo, Ilaria Ferrari, Angela D'Angelo, Derosa G., Cicero A., D'Angelo A., Ragonesi P.D., Ciccarelli L., Piccinni M.N., Pricolo F., Salvadeo S.A., Ferrari I., Gravina A., and Fogari R.
- Subjects
Blood Glucose ,Leptin ,Male ,medicine.medical_specialty ,Physiology ,Tetrazoles ,Blood Pressure ,Type 2 diabetes ,Benzoates ,Body Mass Index ,Rosiglitazone ,Insulin resistance ,Irbesartan ,Double-Blind Method ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Telmisartan ,Glycemic ,medicine.diagnostic_test ,business.industry ,Tumor Necrosis Factor-alpha ,Biphenyl Compounds ,Middle Aged ,medicine.disease ,Lipids ,Endocrinology ,Diabetes Mellitus, Type 2 ,Benzimidazoles ,Female ,Thiazolidinediones ,Metabolic syndrome ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,Lipid profile ,business ,Angiotensin II Type 1 Receptor Blockers ,medicine.drug - Abstract
The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.
- Published
- 2007
95. Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with metformin
- Author
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S. Paniga, L. Ciccarelli, Angela D'Angelo, I. Ferrari, P. D. Ragonesi, M. N. Piccinni, A. Gravina, Arrigo F G Cicero, S. A. T. Salvadeo, F. Pricolo, L. Montagna, Giuseppe Derosa, Derosa G., D'Angelo A., Ragonesi P.D., Ciccarelli L., Piccinni M.N., Pricolo F., Salvadeo S.A., Montagna L., Gravina A., Ferrari I., Paniga S., and Cicero A
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Type 2 diabetes ,Rosiglitazone ,Double-Blind Method ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Thiazolidinedione ,Aged ,Metabolic Syndrome ,Pioglitazone ,business.industry ,Glitazone ,Middle Aged ,medicine.disease ,Metformin ,Endocrinology ,Postprandial ,Diabetes Mellitus, Type 2 ,lipids (amino acids, peptides, and proteins) ,Drug Therapy, Combination ,Female ,Thiazolidinediones ,Metabolic syndrome ,business ,medicine.drug - Abstract
Background: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin, whereas the combination of metformin with thiazolidinediones is relatively less studied. The aim of the present study was to assess the differential effect on glycaemic metabolism and lipid variables of the combination of metformin plus pioglitazone or metformin plus rosiglitazone in diabetic patients with metabolic syndrome. Methods: All patients began metformin and were randomized to receive pioglitazone or rosiglitazone for 12 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, homeostasis model assessment index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B. Results: Significant decreases in glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, and postprandial plasma insulin were seen after 9 and 12 months in both groups. Homeostasis model assessment index improved at 12 months in both groups. Significant total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement was observed in pioglitazone group after 12 months, but not in the rosiglitazone group. These variations were significant between groups. Conclusion: The combination of metformin plus thiazolidinediones was able to improve glycaemic control compared with previous therapy. Pioglitazone was associated with a significant improvement in lipid and lipoprotein variables.
- Published
- 2007
96. Effects of rosiglitazone and pioglitazone combined with metformin on the prothrombotic state of patients with type 2 diabetes mellitus and metabolic syndrome
- Author
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P. D. Ragonesi, Simona Galli, Alessia Gravina, Arrigo F G Cicero, M. N. Piccinni, Ilaria Ferrari, Angela D'Angelo, S. A. T. Salvadeo, Giuseppe Derosa, S. Paniga, Fabio Pricolo, Lorenza Montagna, Leonardina Ciccarelli, Derosa G., Dangelo A., Ragonesi P.D., Ciccarelli L., Piccinni M.N., Pricolo F., Salvadeo S., Montagna L., Gravina A., Ferrari I., Galli S., Paniga S., and Cicero A
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,030226 pharmacology & pharmacy ,Biochemistry ,Rosiglitazone ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Fibrinolysis ,Plasminogen Activator Inhibitor 1 ,Medicine ,Humans ,Hypoglycemic Agents ,Thrombophilia ,Metabolic Syndrome ,Pioglitazone ,business.industry ,Biochemistry (medical) ,Type 2 Diabetes Mellitus ,Glitazone ,Cell Biology ,General Medicine ,Middle Aged ,medicine.disease ,Metformin ,Endocrinology ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Female ,Thiazolidinediones ,Prothrombotic state ,Metabolic syndrome ,business ,Plasminogen activator ,Homeostasis ,medicine.drug - Abstract
In this multicentre, randomized, double-blind, controlled, parallel-group trial, 103 patients with type 2 diabetes mellitus and metabolic syndrome were randomized to receive one of two thiazolidinediones – pioglitazone or rosiglitazone – in combination with 1500 mg/day of metformin, increasing up to 3000 mg/day, for 12 months. Anthropometric, metabolic, coagulation and fibrinolysis parameters were assessed at baseline and after 3, 6, 9 and 12 months. Significant decreases in glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose levels were seen after 9 and 12 months in both groups, and significant decreases in fasting plasma insulin and post-prandial plasma insulin levels were seen after 12 months in both groups. In both groups, improvement in the homeostasis model assessment index compared with baseline was obtained only after 12 months. Plasminogen activator inhibitor-1 levels were significantly lower in both groups after 12 months compared with baseline values. In patients with type 2 diabetes mellitus and metabolic syndrome, the combination of metformin plus thiazolidinediones improved glycaemic control and produced a slight but significant reduction in plasminogen activator inhibitor-1 levels.
- Published
- 2006
97. Thiazolidinedione effects on blood pressure in diabetic patients with metabolic syndrome treated with glimepiride
- Author
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Roberto Fogari, M. Ghelfi, Mario N. Piccinni, Ilaria Ferrari, Arrigo F G Cicero, Angela D'Angelo, Antonio Vittorino Gaddi, Sibilla A T Salvadeo, Lorenza Montagna, Fabio Pricolo, Leonardina Ciccarelli, Pietro D. Ragonesi, Giuseppe Derosa, Derosa G., Cicero A., D’Angelo A., Gaddi A., Ragonesi P.D., Piccinni M.N., Salvadeo S., Ciccarelli L., Pricolo F., Ghelfi M., Ferrari I., Montagna L., and Fogari R.
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,Blood Pressure ,Gastroenterology ,Body Mass Index ,Rosiglitazone ,chemistry.chemical_compound ,Double-Blind Method ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Glycemic ,Glycated Hemoglobin ,Pioglitazone ,business.industry ,Glimepiride ,Thiazolidinedione ,Type 2 diabetes ,Middle Aged ,medicine.disease ,Endocrinology ,Postprandial ,Blood pressure ,Sulfonylurea Compounds ,chemistry ,Diabetes Mellitus, Type 2 ,Female ,Thiazolidinediones ,Glycated hemoglobin ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
The aim of our study was to compare the long-term effect of pioglitazone and rosiglitazone on blood pressure control of diabetic patients with metabolic syndrome treated with glimepiride. We evaluated 91 type 2 diabetic patients with metabolic syndrome. All were required to have been diagnosed as diabetic for at least 6 months, and to have failed to achieve glycemic control by dietary changes and the maximum tolerated dose of the oral hypoglycemic agents sulfonylureas or metformin. All patients took a fixed dose of 4 mg/day glimepiride. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) for 12 months in a randomized, double-blind fashion, and evaluated body mass index (BMI), glycemic control, blood pressure and heart rate (HR) throughout the treatment period. A total of 87 patients completed the study and were randomized to receive double-blind treatment with pioglitazone or rosiglitazone. An increase in BMI was observed after 12 months (p < 0.05) in both groups. After 9 and 12 months, there were significant decreases in glycated hemoglobin (HbA(1c)), mean fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), and postprandial plasma insulin (PPI) in both treatment groups (p < 0.05 at 9 months and p < 0.01 at 12 months for all parameters). Furthermore, homeostasis model assessment index (HOMA index) improvement was obtained at 9 and 12 months (p < 0.05 and p < 0.01, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05, respectively) was observed in both groups after 12 months. There were no significant changes in transaminases at any point during the study. We can conclude that the association of a thiazolinedione to the glimepiride treatment of type 2 diabetic subjects with metabolic syndrome is associated to a significant improvement in the long-term blood pressure control, related to a reduction in insulin-resistance.
- Published
- 2006
98. Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial
- Author
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M. Ghelfi, Elena Fogari, Giuseppe Derosa, Arrigo F G Cicero, S. A. T. Salvadeo, Leonardina Ciccarelli, Ilaria Ferrari, M. N. Piccinni, A.V. Gaddi, Derosa G, Gaddi AV, Piccinni MN, Salvadeo S, Ciccarelli L, Fogari E, Ghelfi M, Ferrari I, and Cicero AF.
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Body Mass Index ,Rosiglitazone ,Endocrinology ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Humans ,Hypoglycemic Agents ,Medicine ,Glycated Hemoglobin ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Lipids ,Hypoglycemia ,Metformin ,Drug Combinations ,Glimepiride ,Sulfonylurea Compounds ,Treatment Outcome ,Postprandial ,Diabetes Mellitus, Type 2 ,Female ,Thiazolidinediones ,Metabolic syndrome ,business ,Lipid profile ,medicine.drug - Abstract
Aim: Accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. The aim of our study is to evaluate the differential effect on glucose and lipid parameters of the association between glimepiride plus metformin and rosiglitazone plus metformin in patients affected by type 2 diabetes and metabolic syndrome. Methods: Patients were enroled, evaluated and followed at two Italian centres. We evaluated 99 type 2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males and 24 females, aged 52 +/- 5 with glimepiride; 25 males and 23 females, aged 54 +/- 4 with cglitazone). All were required to have been diagnosed as being diabetic for at least 6 months and did not have glycaemic control with diet and oral hypoglycaemic agents such as sulphonylureas or metformin, both to the maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day. We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We evaluated body mass index (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein B (Apo B)] during 12 months of this treatment. Results: A total of 95 patients completed the study. Significant BMI decrease was observed at 12 months in glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p < 0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group was observed. Furthermore, homeostasis model assessment index improvement was obtained only at 9 and 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was present in glimepiride group after 12 months compared with the baseline values, and these variations were significant (p < 0.05) between groups. Of the 95 patients who completed the study, 8.5% of patients in glimepiride group and 12.5% of patients in rosiglitazone group had side-effects (p = not significant). Four patients had transient side-effects in glimepiride group and six patients in rosiglitazone group. Altogether, we did not have statistically significant changes in transaminases. Conclusions: The rosiglitazone-metformin association significantly improve the long-term control of all insulin-resistance-related parameters in comparison with the glimepiride-metformin-treated group. On the other side, glimepiride treatment is associated to a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients.
- Published
- 2006
99. Long-term effect of glimepiride and rosiglitazone on non-conventional cardiovascular risk factors in metformin-treated patients affected by metabolic syndrome: a randomized, double-blind clinical trial
- Author
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M. Ghelfi, Elena Fogari, Antonio Vittorino Gaddi, Leonardina Ciccarelli, Ilaria Ferrari, Arrigo F G Cicero, Giuseppe Derosa, Derosa G, Gaddi AV, Ciccarelli L, Fogari E, Ghelfi M, Ferrari I, and Cicero AF.
- Subjects
Blood Glucose ,Male ,Time Factors ,endocrine system diseases ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Biochemistry ,Gastroenterology ,Cardiovascular System ,Body Mass Index ,0302 clinical medicine ,Risk Factors ,Homocysteine ,Metabolic Syndrome ,biology ,General Medicine ,Lipoprotein(a) ,Middle Aged ,Metformin ,Cholesterol ,Cardiovascular Diseases ,030220 oncology & carcinogenesis ,Female ,Rosiglitazone ,medicine.drug ,medicine.medical_specialty ,03 medical and health sciences ,Insulin resistance ,Double-Blind Method ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Glycated Hemoglobin ,business.industry ,Biochemistry (medical) ,Cell Biology ,medicine.disease ,Glimepiride ,Endocrinology ,Sulfonylurea Compounds ,biology.protein ,Thiazolidinediones ,Metabolic syndrome ,Insulin Resistance ,business - Abstract
We evaluated the effect of glimepiride plus metformin and rosiglitazone plus metformin on glucose, and on cardiovascular risk parameters such as lipoprotein(a) (Lp[a]) and homocysteine (HCT) in patients with type 2 diabetes and metabolic syndrome. Ninety-nine patients in the multicentre, randomized, double-blind study took metformin (1500 mg/day) plus glimepiride (2 mg/day) or rosiglitazone (4 mg/day) for 12 months. Changes in body mass index, glycosylated haemoglobin (HbA1c), Lp(a) and HCT were primary efficacy variables. Fasting plasma glucose (FPG), post-prandial plasma glucose (PPG) and homeostasis model assessment index were also used to assess efficacy. On average, HbA1c decreased by 9.1% and 8.1%, FPG decreased by 7.3% and 10.9%, and PPG decreased by 7.6% and 10.5%, respectively, in the glimepiride and rosiglitazone groups after 12 months. Patients receiving rosiglitazone experienced more rapid improvement in glycaemic control than those on glimepiride, and showed a significant improvement in insulin resistance-related parameters. There was a statistically significant decrease in basal homocysteinaemia in glimepiride-treated patients (−27.3%), but not in rosiglitazone-treated patients. Rosiglitazone plus metformin significantly improved long-term control of insulin resistance-related parameters compared with glimepiride plus metformin, although glimepiride treatment was associated with a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients, and with significant improvements in non-traditional risk factors for cardiovascular disease, such as basal homocysteinaemia and plasma Lp(a) levels.
- Published
- 2005
100. Effects of doxazosin and irbesartan on blood pressure and metabolic control in patients with type 2 diabetes and hypertension
- Author
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Giuseppe Derosa, Amedeo Mugellini, Arrigo F G Cicero, Roberto Fogari, Antonio Vittorino Gaddi, Leonardina Ciccarelli, Derosa G, Cicero AF, Gaddi A, Mugellini A, Ciccarelli L, and Fogari R.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Tetrazoles ,Blood Pressure ,Type 2 diabetes ,urologic and male genital diseases ,Irbesartan ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,medicine ,Doxazosin ,Humans ,Pharmacology ,Analysis of Variance ,medicine.diagnostic_test ,business.industry ,Biphenyl Compounds ,Middle Aged ,medicine.disease ,Blood pressure ,Endocrinology ,Diabetes Mellitus, Type 2 ,Metabolic control analysis ,Hypertension ,Female ,Hemoglobin ,Cardiology and Cardiovascular Medicine ,Lipid profile ,business ,medicine.drug - Abstract
The objective of this trial was to compare the metabolic effects of long-term treatment with doxazosin to those of irbesartan in patients with type 2 diabetes and hypertension. We evaluated 96 hypertensive diabetic patients who were randomized to 12 months of double-blind treatment with doxazosin 4 mg/d or irbesartan 300 mg/d. At the end of the study, systolic and diastolic blood pressure (SBP and DBP) were significantly reduced from 152 to 140 mm Hg and from 97 to 87 mm Hg, respectively, with doxazosin (P < 0.01). SBP and DBP were reduced from 150 to 134 mm Hg and from 94 to 83 mm Hg, respectively, with irbesartan (P < 0.01). Irbesartan had significantly better antihypertensive efficacy than doxazosin (P < 0.05). Doxazosin had the greatest effect on glucose metabolism and lipid parameters, with significant (P
- Published
- 2005
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