170 results on '"Roberto Testa"'
Search Results
2. Author Correction: Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes
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Elena Marasco, Giuseppe Passarino, Chiara Pirazzini, Claudio Franceschi, Cristina Giuliani, Maria De Luca, Roberto Testa, Anna Rita Bonfigli, Paolina Crocco, Fabiola Olivieri, F. Romagnoli, Alberto Montesanto, Giuseppina Rose, and Paolo Garagnani
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medicine.medical_specialty ,Multidisciplinary ,business.industry ,lcsh:R ,Haplotype ,MEDLINE ,lcsh:Medicine ,Type 2 diabetes ,medicine.disease ,Erythropoietin ,Internal medicine ,Cohort ,medicine ,lcsh:Q ,lcsh:Science ,business ,All cause mortality ,medicine.drug - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
3. Physical Activity Modulates the Overexpression of the Inflammatory miR-146a-5p in Obese Patients
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Emanuela Mensà, Sara Rossi, Marta Piroddi, Francesco Galli, Maria Cristina Albertini, Gabriele Cruciani, Pierangelo Torquato, Pierpaolo De Feo, Desirée Bartolini, Fabiola Olivieri, Angelo Russo, and Roberto Testa
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Waist ,business.industry ,medicine.medical_treatment ,Clinical Biochemistry ,Inflammation ,Cell Biology ,medicine.disease ,Biochemistry ,Obesity ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,Cytokine ,Internal medicine ,Cohort ,Genetics ,medicine ,Biomarker (medicine) ,medicine.symptom ,Metabolic syndrome ,business ,Molecular Biology - Abstract
Specific microRNAs (miRs), including the "angio-miR-126" and the "inflamma-miR-146a-5p," have been proposed as biomarkers and even therapeutic targets of obesity-associated metabolic diseases. Physical activity, a key measure of prevention for obesity and its complications, is reported to influence the expression of these miRs. In this study, we investigate whether a physical activity program proven to improve metabolic parameters in obese patients can correct the circulating levels of these miRs. Plasma miR-126 and miR-146a-5p were measured in a cohort of obese patients (n = 31, 16F + 15M) before and after the 3-month physical activity program of the CURIAMO trial (registration number for clinical trials: ACTRN12611000255987) and in 37 lean controls (24F + 13M). miR-146a-5p, but not miR-126, was significantly increased in obese patients as compared with lean controls and decreased in approximately two-thirds of the participants post-intervention with a response that positively correlated with pre-intervention levels of this miR. Waist circumference, the inflammatory cytokine IL-8 and lipid parameters, principally total cholesterol, showed the strongest correlation with both the baseline levels and post-intervention correction of miR-146a-5p. Post-hoc analysis of experimental data supports the use of miR-146a-5p as a biomarker and predictor of the clinical response to physical activity in obese patients. Furthermore, miR-146a-5p expression was confirmed to increase together with that of the inflammatory genes TLR4, NF-κB, IL-6, and TNF-α in LPS-stimulated human mononuclear leukocytes. In conclusion, the inflamma-miR-146a-5p can serve as a personalized predictor of clinical outcome in obese patients entering physical activity weight-reduction programs. © 2018 IUBMB Life, 70(10):1012-1022, 2018.
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- 2018
4. Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes
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Paolina Crocco, Elena Marasco, Paolo Garagnani, F. Romagnoli, Cristina Giuliani, Alberto Montesanto, Roberto Testa, Fabiola Olivieri, Giuseppina Rose, Anna Rita Bonfigli, Claudio Franceschi, Maria De Luca, Giuseppe Passarino, Chiara Pirazzini, Montesanto A., Bonfigli A.R., De Luca M., Crocco P., Garagnani P., Marasco E., Pirazzini C., Giuliani C., Romagnoli F., Franceschi C., Passarino G., Testa R., Olivieri F., and Rose G.
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0301 basic medicine ,Male ,medicine.medical_specialty ,Linkage disequilibrium ,Genetic predisposition to disease ,lcsh:Medicine ,Type 2 diabetes ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Genetic variability ,Author Correction ,lcsh:Science ,Erythropoietin ,Aged ,Proportional Hazards Models ,TD2, genetic, Italian population, T2D association genotypes ,Multidisciplinary ,Proportional hazards model ,business.industry ,lcsh:R ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Italy ,Haplotypes ,Cohort ,Female ,lcsh:Q ,business ,030217 neurology & neurosurgery ,Kidney disease ,medicine.drug - Abstract
Type-2 Diabetes (T2D), diabetic complications, and their clinical risk factors harbor a substantial genetic component but the genetic factors contributing to overall diabetes mortality remain unknown. Here, we examined the association between genetic variants at 21 T2D-susceptibility loci and all-cause mortality in an elderly cohort of 542 Italian diabetic patients who were followed for an average of 12.08 years. Univariate Cox regression analyses detected age, waist-to-hip ratio (WHR), glycosylated haemoglobin (HbA1c), diabetes duration, retinopathy, nephropathy, chronic kidney disease (CKD), and anaemia as predictors of all-cause mortality. When Cox proportional hazards multivariate models adjusted for these factors were run, three erythropoietin (EPO) genetic variants in linkage disequilibrium (LD) with each other (rs1617640-T/G, rs507392-T/C and rs551238-A/C) were significantly (False Discovery Rate EPO gene is an independent predictor of mortality in patients with T2D. Thus, understanding the mechanisms by which the genetic variability of EPO affects the mortality of T2D patients may provide potential targets for therapeutic interventions to improve the survival of these patients.
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- 2019
5. Randomized, double-blind, placebo-controlled trial to evaluate the effect of Helicobacter pylori eradication on glucose homeostasis in type 2 diabetic patients
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Roberto Festa, Antonio Ceriello, Roberto Testa, Fabiola Olivieri, Massimo Boemi, Patrizia Bonazzi, Gabriele Brandoni, Anna Rita Bonfigli, Liana Spazzafumo, and Stefano Genovese
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Blood Glucose ,Male ,Time Factors ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Placebo-controlled study ,Medicine (miscellaneous) ,Type 2 diabetes ,Gastroenterology ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Homeostasis ,Insulin ,Glucose homeostasis ,Nutrition and Dietetics ,biology ,Esomeprazole ,Middle Aged ,Anti-Bacterial Agents ,Treatment Outcome ,Italy ,Host-Pathogen Interactions ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,030209 endocrinology & metabolism ,macromolecular substances ,Drug Administration Schedule ,Helicobacter Infections ,03 medical and health sciences ,Insulin resistance ,Double-Blind Method ,Clarithromycin ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Aged ,Helicobacter pylori ,business.industry ,Amoxicillin ,Proton Pump Inhibitors ,medicine.disease ,biology.organism_classification ,Endocrinology ,Diabetes Mellitus, Type 2 ,Insulin Resistance ,business ,Biomarkers - Abstract
Background and aims Literature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. Methods and results A randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p ITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. Conclusion To our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. Trial registration number: ACTRN12609000255280 ( https://www.anzctr.org.au/ ).
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- 2016
6. The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin functions as antioxidant on human endothelial cells exposed to chronic hyperglycemia and metabolic high-glucose memory
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Antonio Ceriello, Roberto Testa, Gemma Pujadas, Valeria De Nigris, Lucia La Sala, and Francesco Prattichizzo
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medicine.medical_specialty ,Teneligliptin and sitagliptin ,Endothelium ,Endocrinology, Diabetes and Metabolism ,Apoptosis ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Biology ,medicine.disease_cause ,Antioxidants ,Umbilical vein ,Sitagliptin Phosphate ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Metabolic memory ,DPP-4 inhibitors ,Internal medicine ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Endothelial dysfunction ,Teneligliptin ,Cells, Cultured ,Dipeptidyl peptidase-4 ,Cell Proliferation ,Dipeptidyl-Peptidase IV Inhibitors ,Diabetes ,Endoplasmic Reticulum Stress ,medicine.disease ,Oxidative Stress ,Glucose ,medicine.anatomical_structure ,Hyperglycemia ,Pyrazoles ,Thiazolidines ,Original Article ,High glucose ,Antioxidant ,Oxidative stress ,TXNIP ,medicine.drug - Abstract
Dipeptidyl peptidase-4 inhibitors are widely used in type 2 diabetes. Endothelium plays a crucial role maintaining vascular integrity and function. Chronic exposure to high glucose drives to endothelial dysfunction generating oxidative stress. Teneligliptin is a novel dipeptidyl peptidase-4 inhibitor with antioxidant properties. This study is aimed to verify a potential protective action of teneligliptin in endothelial cells exposed to high glucose. Human umbilical vein endothelial cells were cultured under normal (5 mmol/L) or high glucose (25 mmol/L) during 21 days, or at high glucose during 14 days followed by 7 days at normal glucose, to reproduce the high-metabolic memory state. During this period, different concentrations of teneligliptin (0.1, 1.0 and 3.0 µmol/L) or sitagliptin (0.5 µmol/L) were added to cells. Ribonucleic acid and protein expression were assessed for antioxidant response, proliferation, apoptosis and endoplasmic reticulum stress markers. Teneligliptin promotes the antioxidant response in human umbilical vein endothelial cells, reducing ROS levels and inducing Nrf2-target genes messenger ribonucleic acid expression. Teneligliptin, but not sitagliptin, reduces the expression of the nicotine amide adenine dinucleotide phosphate oxidase regulatory subunit P22 −phox, however, both blunt the high glucose-induced increase of TXNIP. Teneligliptin improves proliferation rates in human umbilical vein endothelial cells exposed to high glucose, regulating the expression of cell-cycle inhibitors markers (P53, P21 and P27), and reducing proapoptotic genes (BAX and CASP3), while promotes BCL2 expression. Teneligliptin ameliorates high glucose-induced endoplasmic reticulum stress reducing the expression of several markers (BIP, PERK, ATF4, CHOP, IRE1a and ATF6). Teneligliptin has antioxidant properties, ameliorates oxidative stress and apoptotic phenotype and it can overcome the metabolic memory effect, induced by chronic exposure to high glucose in human endothelial cells.
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- 2016
7. The simultaneous control of hyperglycemia and GLP-1 infusion normalize endothelial function in type 1 diabetes
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Antonio Ceriello, Valeria De Nigris, Roberto Testa, Lucia La Sala, Gemma Pujadas, Stefano Genovese, Anna Rita Bonfigli, and Annachiara Uccellatore
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Adult ,Blood Glucose ,Male ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Prostaglandin ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Dinoprost ,medicine.disease_cause ,8 iso pgf2α ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Glucagon-Like Peptide 1 ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Infusions, Parenteral ,Vascular Diseases ,Endothelial dysfunction ,Glucagon-like peptide 1 receptor ,Type 1 diabetes ,business.industry ,digestive, oral, and skin physiology ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,Glucagon-like peptide-1 ,Oxidative Stress ,Diabetes Mellitus, Type 1 ,chemistry ,Case-Control Studies ,Hyperglycemia ,Female ,Endothelium, Vascular ,business ,hormones, hormone substitutes, and hormone antagonists ,Oxidative stress - Abstract
Background To test the effect of normoglycemia and glucagon-like peptide-1 (GLP-1), alone or in combination, on the possible normalization of endothelial function in type 1 diabetes. Methods Fifteen people with type 1 diabetes participated in three experiments: reaching and maintaining normoglycemia for 4 h; reaching and maintaining hyperglycemia plus GLP-1 infusion for 4 h; and reaching and maintaining normoglycemia for 4 h with simultaneous infusion of GLP-1. Results Both normoglycemia and GLP-1 infusion restored endothelial function and decreased and plasma 8-iso prostaglandin F2α levels. However, only the combination of normoglycemia and GLP-1 was able to normalize endothelial function. Conclusions This study confirms that long-lasting hyperglycemia in type 1 diabetes induces a permanent alteration which contributes to maintaining endothelial dysfunction even when glycemia is normalized, and that in the presence of normoglycemia, GLP-1 can contribute to normalizing endothelial function.
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- 2016
8. Focus on migrants with type 2 diabetes mellitus in European Countries
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Antonio Ceriello, Roberto Testa, Anna Rita Bonfigli, and Stefano Genovese
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Male ,Gerontology ,medicine.medical_specialty ,Population ,Emigrants and Immigrants ,030209 endocrinology & metabolism ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,Health care ,Epidemiology ,Prevalence ,Internal Medicine ,medicine ,Humans ,European Union ,030212 general & internal medicine ,Healthcare Disparities ,education ,Life Style ,Transients and Migrants ,Diabetes Complication ,education.field_of_study ,Health management system ,business.industry ,Mortality rate ,Incidence (epidemiology) ,Type 2 Diabetes Mellitus ,Europe ,Survival Rate ,Diabetes Mellitus, Type 2 ,Emergency Medicine ,Female ,business - Abstract
The prevalence of type 2 diabetes mellitus, one of the major causes of morbility and mortality in Europe, is increasing in all European countries. Diabetes is not distributed equally among all population groups, as higher incidence, appearance of complications, and different mortality rates have been observed among migrants and the native population. These differences may be due to genetic profiles, lifestyle, and utilization of the health care system in different ways. Taking into account that the quantity of migrants is nowadays increasing, mainly in the southern part of Europe, the knowledge of diabetes in migrants through a better collection of data is necessary, considering that few limited epidemiological studies have evaluated the importance of this problem in EU countries. A special effort in developing a comprehensive management for native and immigrant populations in order to prevent and cure diabetes should be mandatory. This activity could be helpful to limit the incidence of future diabetes complications and to avoid the consequent burden of the health care system along with a control on its costs. It is clear that diabetes complication prevention is essential for long-term sustainability of the health care system.
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- 2015
9. The pivotal role of high glucose-induced overexpression of PKCβ in the appearance of glucagon-like peptide-1 resistance in endothelial cells
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Antonio Ceriello, Roberto Testa, Lucia La Sala, Stefano Genovese, Valeria De Nigris, and Gemma Pujadas
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0301 basic medicine ,medicine.medical_specialty ,Indoles ,Cell Survival ,Endocrinology, Diabetes and Metabolism ,Receptor expression ,Cell ,Biology ,Glucagon-Like Peptide-1 Receptor ,Umbilical vein ,Ruboxistaurin ,Maleimides ,03 medical and health sciences ,chemistry.chemical_compound ,Endocrinology ,Glucagon-Like Peptide 1 ,Internal medicine ,Protein Kinase C beta ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Enzyme Inhibitors ,Endothelial dysfunction ,Receptor ,Cells, Cultured ,Cell Proliferation ,Endoplasmic Reticulum Stress ,medicine.disease ,Cell biology ,Glucose ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Apoptosis ,Unfolded protein response ,Reactive Oxygen Species - Abstract
Recently, it has been demonstrated that Glucagon-like peptide-1 (GLP-1) has a protective effect on endothelial cells. Our hypothesis is that this GLP-1 protective effect is partly lost when the cells are exposed to sustained high glucose concentrations. Human umbilical vein endothelial cells (HUVECs) were cultured for 21 days in normal glucose (5 mmol/L, NG) or high glucose (25 mmol/L glucose, HG). GLP-1 (7-37) and Ruboxistaurin were added at 50 and 500 nM, respectively, alone or in combination, 1 h before cell harvesting. Analysis of GLP-1 receptor protein levels, as well as of the gene expression of different ER stress-related genes, proliferation markers, antioxidant cell response-related genes, and PKA subunits, was performed. ROS production was also measured in HUVECs exposed to mentioned treatments. GLP-1 receptor expression was reduced in HUVECs exposed to chronic high glucose concentrations but was partially restored by a chemical PKCβ-specific inhibitor. GLP-1, added as an acute treatment in endothelial cells, had the capacity to induce the expression of Nrf2-detoxifying enzyme targets, to increase transcription levels of scavenger genes, to attenuate the expression of high glucose-induced PKA subunits, ER stress and also the apoptotic phenotype of HUVECs; these effects occured only when high glucose-induced PKCβ overexpression was reduced by Ruboxistaurin. In a similar manner, ROS production induced by high glucose was reduced by GLP-1 in the presence of PKCβ inhibitor. This study suggests that an increase in PKCβ, induced by high glucose, could have a role in endothelial GLP-1 resistance, reducing GLP-1 receptor levels and disrupting the GLP-1 canonical pathway.
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- 2015
10. ZnT8 Arg325Trp polymorphism influences zinc transporter expression and cytokine production in PBMCs from patients with diabetes
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Marco Malavolta, Francesco Piacenza, N. Gasparini, Anna Rita Bonfigli, Lorenzo Nisi, L. Chiodi, Mauro Provinciali, Roberto Testa, Roberta Galeazzi, L. Costarelli, Gianfranco Boccoli, Andrea Basso, and R. Giacconi
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0301 basic medicine ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Genotype ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Inflammation ,Type 2 diabetes ,Zinc Transporter 8 ,Peripheral blood mononuclear cell ,03 medical and health sciences ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Cation Transport Proteins ,Aged ,Aged, 80 and over ,Polymorphism, Genetic ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Zinc ,030104 developmental biology ,Cytokine ,chemistry ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Leukocytes, Mononuclear ,Cytokines ,Female ,medicine.symptom ,business ,Carrier Proteins ,Homeostasis - Abstract
Aims ZnT8 Arg325Trp polymorphism has been associated with type 2 diabetes (T2DM) susceptibility. The Arg-325 risk variant shows accelerated zinc (Zn) transport kinetic and reduced glucose-stimulated insulin secretion in pancreatic cells. However, it remains unexplored the role of Znt8 polymorphism in the regulation of Zn homeostasis and inflammatory response in peripheral blood mononuclear cells (PBMCs) from T2DM patients. Methods and results A total of 556 healthy controls and 413 T2DM patients were genotyped for ZnT8 Arg325Trp polymorphism confirming the association of Arg-325 variant with an increased T2DM risk (OR = 1.35 95% C.I: 1.10–1.66; p = 0.0044). Moreover, PBMCs from Arg/Arg T2DM subjects showed increased intracellular free Zn, higher gene expression of Metallothioneins, Znt1, Znt8, Zip2 genes, and reduced Znt4 and Znt7. Higher release of IL-1α, IL-1β, IFN-γ, IL-12p70 and TNF-α and a reduced IL-10 secretion after lipopolysaccharide (LPS) stimulation were observed in PBMCs from Arg/Arg T2DM carriers as compared to subjects with the Trp variant. Conclusions Our data provide evidence of a substantial different Zn homeostasis regulation between Znt8 Arg-325 and Trp-325 carriers in PBMCs from T2DM patients. Moreover, Znt8 Arg-325 risk variant shows an enhanced inflammatory response upon LPS stimulation that might aggravate insulin resistance and the progression of diabetes cardiovascular complications.
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- 2018
11. Serum levels of adipocytokines in psoriasis patients receiving tumor necrosis factor-αinhibitors: results of a retrospective analysis
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Giulia Ganzetti, Annarita Bonfigli, Katia Giuliodori, Annamaria Offidani, Maurizio Marra, Roberto Testa, and Anna Campanati
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Adult ,Leptin ,Male ,medicine.medical_specialty ,Adipokine ,Dermatology ,Severity of Illness Index ,Body Mass Index ,Etanercept ,Waist–hip ratio ,Adipokines ,Psoriasis ,Internal medicine ,medicine ,Humans ,Resistin ,Nicotinamide Phosphoribosyltransferase ,Retrospective Studies ,Adiponectin ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Waist-Hip Ratio ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Body Weight ,Adalimumab ,Case-control study ,Middle Aged ,medicine.disease ,Endocrinology ,Case-Control Studies ,Female ,business ,Body mass index - Abstract
Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases.This study was conducted to evaluate the effects of tumor necrosis factor-α (TNF-α) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis.Serum levels of adiponectin, resistin, visfatin, leptin, TNF-α, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF-α inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits.At baseline, mean serum levels of TNF-α, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an anti-inflammatory adipocytokine, were only mildly increased and persisted at a significantly lower level than in healthy controls (P0.005).Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF-α inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines.
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- 2015
12. Zofenopril and Ramipril in Combination with Acetyl Salicylic Acid in Postmyocardial Infarction Patients with Left Ventricular Systolic Dysfunction: A Retrospective Analysis of the SMILE-4 Randomized, Double-Blind Study in Diabetic Patients
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BORGHI, CLAUDIO, AMBROSIONI, ETTORE, Omboni, Stefano, Novo, Salvatore, Vinereanu, Dragos, Ambrosio, Giuseppe, Dimitrios, Alexopolulus, Ioannis, Nanas, Marco, Agrusta, Antonio, Barsotti, Serena, Bergerone, Luigi, Caliendo, Pio, Caso, Antonio, Castello, Domenico, Cianflone, Tommaso, Cipolla, Gaetano, De Ferrari, Giuseppe, De Nittis, Livio, Dei Cas, Paolo, Di Pasquale, Rosario, Evola, Luciano, Fattore, Raffaele, Ferrante, Antonio, Fiscella, Achille, Gaspardone, Giuseppe, Ielasi, Niccoló, Marchionni, Giancarlo, Marenzi, Filippo, Marte, Federico, Miccoli, Patrizia, Noussan, Mario, Orlandi, Giancarlo, Piovaccari, Maurizio, Porcu, Patrizia, Presbitero, Antonio, Raviele, Emiliano, Renaldini, Jorge, Salerno Uriarte, Giovanni, Storti, Corrado, Tamburino, Pierfranco, Terrosu, Roberto, Testa, Rita, Trinchero, Bernardino, Tuccillo, Ludovico, Vasquez, Quinto, Villani Giovanni, Garcia, Alvés Mario, Aurora, Andrade, Silva, Cardoso, Ilidio, Moreira Joseà, Catalina, Arsenescu Georgescu, Mircea, Cinteza, Maria, Dorobantu, Dominic, Ionescu, Ioan, Manitiu, Florin, Ortan, Calin, Pop, Mariana, Radoi, Yuriy, Alexandrovich Vasyuk, Victor, Avenirovitch Kostenko, Yuriy, Borisovich Karpov, Vira, Iosifovna Tseluiko, Abram, Lvovich Syrkin, Boris, Mikhailovich Goloschekin, Evgeniy, Mikhaylovich Nifontov, Sergey, Nikolaevich Tereschenko, Natalia, Nikolaevna Burova, Konstantin, Nikolayevich Zrazhevsky, Grigory, Pavlovich Arutuynov, Valentin, Sergeevich Moiseev, Leonid, Victorovich Rudenko, Alexander, Yurievich Vishnevsky, Diaz, D. L. Y. De La Yera, Fernández, Romero, Cevat, Kirma, Kayikcioglu, Meral, Abdurrahman, Oğuzhan, Dilek, Ural Komsuoglu, Olena, Ankindinovna Koval, Alexan, Nikolaevich Parkhomenko, Igor, Petrovich Vakalyuk, Mykola, Tihonovich Vatutin, Valerii, Vladimirovich Batushkin, Borghi, Claudio, Omboni, Stefano, Novo, Salvatore, Vinereanu, Drago, Ambrosio, Giuseppe, Ambrosioni, Ettore, Dimitrios, Alexopolulu, Ioannis, Nana, Marco, Agrusta, Antonio, Barsotti, Serena, Bergerone, Luigi, Caliendo, Pio, Caso, Antonio, Castello, Domenico, Cianflone, Tommaso, Cipolla, Gaetano, De Ferrari, Giuseppe, De Nitti, Livio, Dei Ca, Paolo, Di Pasquale, Rosario, Evola, Luciano, Fattore, Raffaele, Ferrante, Antonio, Fiscella, Achille, Gaspardone, Giuseppe, Ielasi, Niccoló, Marchionni, Giancarlo, Marenzi, Filippo, Marte, Federico, Miccoli, Patrizia, Noussan, Mario, Orlandi, Giancarlo, Piovaccari, Maurizio, Porcu, Patrizia, Presbitero, Antonio, Raviele, Emiliano, Renaldini, Jorge, Salerno Uriarte, Giovanni, Storti, Corrado, Tamburino, Pierfranco, Terrosu, Roberto, Testa, Rita, Trinchero, Bernardino, Tuccillo, Ludovico, Vasquez, Quinto, Villani Giovanni, Garcia, Alvés Mario, Aurora, Andrade, Silva, Cardoso, Ilidio, Moreira Joseà, Catalina, Arsenescu Georgescu, Mircea, Cinteza, Maria, Dorobantu, Dominic, Ionescu, Ioan, Manitiu, Florin, Ortan, Calin, Pop, Mariana, Radoi, Yuriy, Alexandrovich Vasyuk, Victor, Avenirovitch Kostenko, Yuriy, Borisovich Karpov, Vira, Iosifovna Tseluiko, Abram, Lvovich Syrkin, Boris, Mikhailovich Goloschekin, Evgeniy, Mikhaylovich Nifontov, Sergey, Nikolaevich Tereschenko, Natalia, Nikolaevna Burova, Konstantin, Nikolayevich Zrazhevsky, Grigory, Pavlovich Arutuynov, Valentin, Sergeevich Moiseev, Leonid, Victorovich Rudenko, Alexander, Yurievich Vishnevsky, Diaz, D.L.Y.De La Yera, Fernández, Romero, Cevat, Kirma, Kayikcioglu, Meral, Abdurrahman, Oğuzhan, Dilek, Ural Komsuoglu, Olena, Ankindinovna Koval, Alexan, Nikolaevich Parkhomenko, Igor, Petrovich Vakalyuk, Mykola, Tihonovich Vatutin, Valerii, Vladimirovich Batushkin, on behalf of the SMILE-4 Working, Party, and Cianflone, Domenico
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Male ,Captopril ,Diabetic Cardiomyopathies ,Myocardial Infarction ,Infarction ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,chemistry.chemical_compound ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Diabetes mellitus ,Ramipril ,Retrospective Studie ,Cardiovascular Disease ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Myocardial infarction ,Diabetic Cardiomyopathie ,Randomized Controlled Trials as Topic ,Aspirin ,Left ventricular dysfunction ,General Medicine ,Acetyl salicylic acid ,Acute myocardial infarction ,Angiotensin-converting enzyme inhibitors ,Zofenopril ,Cardiology and Cardiovascular Medicine ,Pharmacology ,Middle Aged ,Cardiovascular Diseases ,Cardiology ,Platelet aggregation inhibitor ,Drug Therapy, Combination ,Female ,medicine.drug ,Human ,medicine.medical_specialty ,Diabetes mellitu ,Systole ,03 medical and health sciences ,Internal medicine ,Humans ,Aged ,Retrospective Studies ,business.industry ,Platelet Aggregation Inhibitor ,Angiotensin-Converting Enzyme Inhibitor ,medicine.disease ,chemistry ,Angiotensin-converting enzyme inhibitor ,business ,Mace ,Platelet Aggregation Inhibitors - Abstract
Summary Objective In the SMILE-4 study, zofenopril + acetyl salicylic acid (ASA) was more effective than ramipril + ASA on 1-year prevention of major cardiovascular events (MACE) in patients with acute myocardial infarction complicated by left ventricular dysfunction. In this retrospective analysis, we evaluated drug efficacy in subgroups of patients, according to a history of diabetes mellitus. Methods The primary study endpoint was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Diabetes was defined according to medical history (previous known diagnosis). Results A total of 562 of 693 (81.0%) patients were classified as nondiabetics and 131 (18.9%) as diabetics. The adjusted rate of MACE was lower under zofenopril than under ramipril in both nondiabetics [27.9% vs. 34.9% ramipril; odds ratio, OR and 95% confidence interval: 0.55 (0.35, 0.86)] and diabetics [30.9% vs. 41.3%; 0.56 (0.18, 1.73)], although the difference was statistically significant only for the nondiabetic group (P = 0.013). Zofenopril was superior to ramipril as regards to the primary study endpoint in the subgroup of 157 patients with uncontrolled blood glucose (≥126 mg/dL), regardless of a previous diagnosis of diabetes [0.31 (0.10, 0.90), P = 0.030]. Zofenopril significantly reduced the risk of hospitalization for cardiovascular causes in both nondiabetics [0.64 (0.43, 0.96), P = 0.030] and diabetics [0.38 (0.15, 0.95), P = 0.038], whereas it was not better than ramipril in terms of prevention of cardiovascular deaths. Conclusions This retrospective analysis of the SMILE-4 study confirmed the good efficacy of zofenopril plus ASA in the prevention of long-term MACE also in the subgroup of patients with diabetes mellitus.
- Published
- 2016
13. Glycated albumin: correlation to HbA1c and preliminary reference interval evaluation
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Elena Guerra, Antonio Ceriello, Anna Rita Bonfigli, Stefano Genovese, Michela Cucchi, Nicola Di Gaetano, Ferruccio Ceriotti, Roberto Testa, Gabriele Santini, and Massimo Boemi
- Subjects
Adult ,Glycation End Products, Advanced ,Male ,medicine.medical_specialty ,Adolescent ,Clinical Biochemistry ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Correlation ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glycated albumin ,Text mining ,Reference Values ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Humans ,Glycated Serum Albumin ,Serum Albumin ,Aged ,Aged, 80 and over ,Glycated Hemoglobin ,business.industry ,Biochemistry (medical) ,General Medicine ,Middle Aged ,medicine.disease ,chemistry ,Reference values ,Interval (graph theory) ,Female ,Glycated hemoglobin ,business - Published
- 2016
14. Myocardial bridge as a trigger of Kounis syndrome
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Claudio Marabotti, Elio Venturini, Roberto Testa, Lucia Magni, and Nicholas G. Kounis
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Myocardial bridge ,medicine.medical_specialty ,Acute coronary syndrome ,medicine.diagnostic_test ,Myocardial bridging ,business.industry ,Electrocardiography in myocardial infarction ,Kounis syndrome ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cardiology ,Medicine ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,Electrocardiography - Published
- 2016
15. Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants
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Claudia Dellanoce, Rossella Morandini, Armando Tripodi, Sophie Testa, Emilia Antonucci, Vittorio Pengo, Cristina Legnani, Gualtiero Palareti, Roberto Testa, Daniela Poli, Benilde Cosmi, Oriana Paoletti, and Testa S., Paoletti O, Legnani C, Dellanoce C, Antonucci E, Cosmi B, Pengo V, Poli D, Morandini R, Testa R, Tripodi A, Palareti G
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Pyridones ,Administration, Oral ,030204 cardiovascular system & hematology ,Thrombin time ,Risk Assessment ,Antithrombins ,Dabigatran ,03 medical and health sciences ,0302 clinical medicine ,Rivaroxaban ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Thromboembolism ,Atrial Fibrillation ,medicine ,Humans ,030212 general & internal medicine ,Registries ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Anticoagulant ,Atrial fibrillation ,Hematology ,Middle Aged ,medicine.disease ,Confidence interval ,Treatment Outcome ,Cohort ,Cardiology ,Pyrazoles ,atrial fibrillation, cardiovascular risk, coagulation test, direct oral anticoagulants, thromboembolism, apixaban,dabigatran, rivaroxaban ,Apixaban ,Female ,Blood Coagulation Tests ,Drug Monitoring ,business ,medicine.drug ,Factor Xa Inhibitors ,Preliminary Data - Abstract
Essentials Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently. DOAC specific measurements were performed at trough in patients with atrial fibrillation. Patients who developed thromboembolic events showed lower DOAC plasma levels. This study supports the concept of measuring DOAC levels at steady state. Summary: Background Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C-trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry. Methods DOAC-specific measurements (diluted thrombin time or anti-activated factor II calibrated for dabigatran; anti-activated FX calibrated for rivaroxaban or apixaban) at C-trough were performed locally at steady state within 15–25 days after the start of treatment. For each DOAC, the interval of C-trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow-up were recorded. Results Thromboembolic events (1.8%) occurred in 10 patients who had baseline C-trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C-trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2DS2-VASc score than that of the total patient population: 5.3 (95% confidence interval [CI] 4.3–6.3 versus 3.0 (95% CI 2.9–3.1). Conclusion In this study cohort, thrombotic complications occurred only in DOAC-treated AF patients who had very low C-trough levels, with a relatively high CHA2DS2-VASc score. Larger studies are warranted to confirm these preliminary observations. © 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.
- Published
- 2017
16. The 'Metabolic Memory' Theory and the Early Treatment of Hyperglycemia in Prevention of Diabetic Complications
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Lucia La Sala, Antonio Ceriello, Valeria De Nigris, Francesco Prattichizzo, Roberto Testa, and Anna Rita Bonfigli
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Blood Glucose ,Glycation End Products, Advanced ,medicine.medical_specialty ,Glycosylation ,type 2 diabetes mellitus ,030209 endocrinology & metabolism ,Inflammation ,Review ,030204 cardiovascular system & hematology ,metabolic memory ,Bioinformatics ,medicine.disease_cause ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,Glycation ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Epidemiology ,medicine ,diabetic complications ,Humans ,Hypoglycemic Agents ,Prospective cohort study ,Nutrition and Dietetics ,business.industry ,Type 2 Diabetes Mellitus ,medicine.disease ,Oxidative Stress ,Endocrinology ,Glucose ,Diabetes Mellitus, Type 2 ,Metabolic control analysis ,Hyperglycemia ,Microvessels ,medicine.symptom ,business ,Oxidative stress ,Food Science - Abstract
Several epidemiological and prospective studies suggest that an early intensive control of hyperglycaemia is able to decrease the risk of diabetic micro- and macro-vascular complications. A growing body of experimental evidence supports the concept that the risk for diabetes complications may be linked to oxidative stress, non-enzymatic glycation of proteins, epigenetic changes, and chronic inflammation, laying the foundation for the “metabolic memory” theory. From a clinical point of view, this theory supports the need for a very early aggressive treatment, with the goal of normalizing metabolic control as soon as possible. It may also prove beneficial to introduce therapeutic agents that are able to reduce reactive species and glycation, in addition to presenting better control of glucose levels in patients with diabetes, in order to minimize long-term diabetes complications. In this review, we evaluate the effect of glucose intake and metabolism in the light of this theory.
- Published
- 2017
17. Multicenter evaluation of an enzymatic method for glycated albumin
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Mariarosa Carta, Renata Paleari, Anna Vero, Ferruccio Ceriotti, Elena Guerra, Cinzia Anna Maria Calla, Donata Scribano, Martina Montagnana, Gabriella Lavalle, Francesca Gabriela Martino, Andrea Mosca, Roberto Testa, Claudia Lo Cascio, Gabriele Santini, Marco Moretti, Graziella Bonetti, Nicola Di Gaetano, and Marilisa Ferri
- Subjects
Glycation End Products, Advanced ,medicine.medical_specialty ,diabetes ,glycated albumin ,multicenter evaluation ,Clinical Biochemistry ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Glycated albumin ,Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Internal medicine ,Medicine ,Humans ,Glycated Serum Albumin ,Serum Albumin ,Chromatography ,business.industry ,Biochemistry (medical) ,Glicated Albumin ,Reproducibility of Results ,General Medicine ,Repeatability ,Enzymes ,Endocrinology ,Linear Models ,business ,Blood Chemical Analysis - Abstract
Background The use of glycated albumin (GA) has been proposed as an additional glycemic control marker particularly useful in intermediate-term monitoring and in situation when HbA 1c test is not reliable. Methods We have performed the first multicenter evaluation of the analytical performance of the enzymatic method quantILab Glycated Albumin assay implemented on the most widely used clinical chemistry analyzers (i.e. Abbott Architect C8000, Beckman Coulter AU 480 and 680, Roche Cobas C6000, Siemens ADVIA 2400 and 2400 XPT). Results The repeatability of the GA measurement (expressed as CV, %) implemented in the participating centers ranged between 0.9% and 1.2%. The within-laboratory CVs ranged between 1.2% and 1.6%. A good alignment between laboratories was found, with correlation coefficients from 0.996 to 0.998. Linearity was confirmed in the range from 7.6 to 84.7%. Conclusion The new enzymatic method for glycated albumin evaluated by our investigation is suitable for clinical use.
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- 2017
18. Age-related modulation of plasmatic beta-Galactosidase activity in healthy subjects and in patients affected by T2DM
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Emanuela Mensà, Fabiola Olivieri, Liana Spazzafumo, Roberto Testa, Anna Rita Bonfigli, Lucia Zampini, Antonio Procopio, Giulia Matacchione, Roberto Antonicelli, Massimiliano Bonafè, Paolo Garagnani, Tiziana Galeazzi, Massimo Boemi, Rina Recchioni, Fiorella Marcheselli, Francesco Prattichizzo, Spazzafumo, Liana, Mensà, Emanuela, Matacchione, Giulia, Galeazzi, Tiziana, Zampini, Lucia, Recchioni, Rina, Marcheselli, Fiorella, Prattichizzo, Francesco, Testa, Roberto, Antonicelli, Roberto, Garagnani, Paolo, Boemi, Massimo, Bonafè, Massimiliano, Bonfigli, Anna Rita, Procopio, Antonio Domenico, and Olivieri, Fabiola
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0301 basic medicine ,Gerontology ,medicine.medical_specialty ,business.industry ,Alma mater ,Gerotarget ,aging ,Healthy subjects ,beta galactosidase activity ,Cellular senescence ,Diabetology ,University hospital ,03 medical and health sciences ,Research Paper: Gerotarget (Focus on Aging) ,030104 developmental biology ,Oncology ,Internal medicine ,Age related ,Medicine ,cellular senescence ,In patient ,inflammaging ,type 2 diabetes ,business ,Beta-galactosidase activity - Abstract
// Liana Spazzafumo 1,* , Emanuela Mensa 2,* , Giulia Matacchione 2,* , Tiziana Galeazzi 3 , Lucia Zampini 3 , Rina Recchioni 4 , Fiorella Marcheselli 4 , Francesco Prattichizzo 5 , Roberto Testa 6 , Roberto Antonicelli 7 , Paolo Garagnani 8,9 , Massimo Boemi 10 , Massimiliano Bonafe 8 , Anna Rita Bonfigli 11 , Antonio Domenico Procopio 2,4 and Fabiola Olivieri 2,4 1 Center of Biostatics, INRCA-IRCCS National Institute, Ancona, Italy 2 Department of Clinical and Molecular Sciences, DISCLIMO, Universita Politecnica delle Marche, Ancona, Italy 3 Pediatric Division, Department of Clinical Sciences, Universita Politecnica delle Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy 4 Center of Clinical Pathology and Innovative Therapy, INRCA-IRCCS National Institute, Ancona, Italy 5 Department of Cardiovascular and Metabolic Diseases, IRCCS Multimedica, Sesto San Giovanni, Italy 6 Clinical Laboratory and Molecular Diagnostics, INRCA-IRCCS National Institute, Ancona, Italy 7 UTIC-Cardiology INRCA-IRCCS, National Institute, Ancona, Italy 8 Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy 9 Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden 10 Diabetology Unit, INRCA-IRCCS, National Institute, Ancona, Italy 11 Scientific Direction, INRCA-IRCCS, National Institute, Ancona, Italy * The authors contributed equally to this work Correspondence to: Anna Rita Bonfigli, email: // Keywords : cellular senescence; beta galactosidase activity; type 2 diabetes; aging; inflammaging; Gerotarget Received : August 02, 2017 Accepted : October 04, 2017 Published : October 16, 2017 Abstract β-Galactosidase (β-Gal) activity has been the most extensively utilized biomarker for the detection of cellular senescence. It can be measured also in plasma, and few recent evidence showed an altered plasmatic β-Gal activity in patients affected by some age-related diseases (ARDs). Since T2DM is one of the most common ARDs, we aimed to investigate if plasmatic β-Gal activity is modulated in T2DM patients and if “age” could affect such modulation. To gain mechanistic insights we paralleled this investigation with the evaluation of β-Gal activity in young and senescent endothelial cells (HUVECs) cultured in normo- and hyper-glycaemic environment. A significant age-related increase of plasmatic β-Gal activity was observed in healthy subjects (n. 230; 55-87 years), whereas the enzymatic activity was significantly reduced in T2DM patients (n. 230; 55-96 years) compared to healthy subjects. β-Gal activity detectable both in cells and in the culture medium was significantly increased in senescent cells compared to the younger ones, both under normo- and hyper-glycaemic condition. However, the hyper-glycaemic condition was not associated with an increased β-Gal activity in milieu compared to normo-glycaemic condition. Overall our data reinforce the notion that plasmatic β-Gal activity could be a systemic biomarker of aging, whereas T2DM patients are characterized by a different age-releated trend.
- Published
- 2017
19. Nutritional imbalances linking cellular senescence and type 2 diabetes mellitus
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Antonio Ceriello, Roberto Testa, and Stefano Genovese
- Subjects
medicine.medical_specialty ,Medicine (miscellaneous) ,Inflammation ,Motor Activity ,Bioinformatics ,Nutraceutical ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine ,Hyperinsulinemia ,Animals ,Humans ,Micronutrients ,Life Style ,Cellular Senescence ,Nutrition and Dietetics ,business.industry ,Malnutrition ,Metabolic disorder ,Type 2 Diabetes Mellitus ,medicine.disease ,Obesity ,Disease Models, Animal ,Endocrinology ,Diabetes Mellitus, Type 2 ,medicine.symptom ,business - Abstract
Purpose of review Quality of nutrition plays a central role in illnesses such as diabetes and its complications. Dietary and lifestyle habits may have a strong impact, either worsening or improving the evolution of diabetes mellitus. Some factors, such as obesity, worsen the illness, causing chronic inflammation, lipid metabolic disorder, accelerated atherosclerosis, increased risk for thrombosis, hypertension, hyperinsulinemia, insulin resistance, and cellular senescence. Some other nutritional components, however, have an opposite effect, probably increasing antioxidant defense. Recent findings The effects of nutritional factors on cellular senescence in diabetic patients are described in this review. In particular, we discuss some of the nutritional causes of cellular senescence in diabetes mellitus and focus on different nutraceutical compounds that can affect cellular senescence. Furthermore, relevant mechanisms of action are also described. Summary Diet and nutraceutical factors have important effects on diabetes mellitus. Some molecules, which improve antioxidant defense, may counteract cellular senescence. A good lifestyle with physical activity and good weight control can improve the quality of life in diabetic people; on the contrary, obesity and vitamin deficiencies may worsen the evolution of this illness, even inducing cellular senescence.
- Published
- 2014
20. Simultaneous GLP-1 and Insulin Administration Acutely Enhances Their Vasodilatory, Antiinflammatory, and Antioxidant Action in Type 2 Diabetes
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Antonio Ceriello, Silvia Canivell, Katherine Esposito, Maurizio Rondinelli, Loredana Bucciarelli, Anna Novials, Roberto Testa, Lucia La Sala, Gemma Pujadas, and Stefano Genovese
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Vasodilator Agents ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Anti-Inflammatory Agents ,Type 2 diabetes ,Dinoprost ,Antioxidants ,chemistry.chemical_compound ,Glucagon-Like Peptide 1 ,Hyperinsulinism ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Hyperinsulinemia ,Humans ,Hypoglycemic Agents ,Insulin ,Endothelial dysfunction ,Advanced and Specialized Nursing ,Interleukin-6 ,business.industry ,Nitrotyrosine ,Middle Aged ,medicine.disease ,Intercellular adhesion molecule ,Oxidative Stress ,Clamp ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,Hyperglycemia ,Female ,business - Abstract
OBJECTIVE To test the hypothesis that the simultaneous administration of GLP-1 and insulin may increase their vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes. RESEARCH DESIGN AND METHODS In two groups of persons with type 2 diabetes, two sets of experiments were performed. The first group had two normoglycemic-normoinsulinemic clamps with or without GLP-1 and two normoglycemic-hyperinsulinemic clamps with or without GLP-1. The second group had two hyperglycemic-normoinsulinemic clamps and two hyperglycemic-hyperinsulinemic clamps with or without GLP-1. RESULTS During the normoglycemic-hyperinsulinemic clamp, flow-mediated dilatation (FMD) increased, while soluble intercellular adhesion molecule (sICAM-1), plasma 8-iso-prostaglandin F2α (8-iso-PGF2α), nitrotyrosine, and interleukin (IL)-6 decreased compared with normoglycemic-normoinsulinemic clamp. Similar results were obtained with the infusion of GLP-1 during the normoglycemic-normoinsulinemic clamp. The combination of hyperinsulinemia and GLP-1 in normoglycemia was accompanied by a further FMD increase and sICAM-1, 8-iso-PGF2α, nitrotyrosine, and IL-6 decrease. During the hyperglycemic-normoinsulinemic clamp, FMD significantly decreased, while sICAM-1, 8-iso-PGF2α, nitrotyrosine, and IL-6 significantly increased. When hyperglycemia was accompanied by hyperinsulinemia or by the simultaneous infusion of GLP-1, these phenomena were attenuated. The simultaneous presence of hyperinsulinemia and GLP-1 had an increased beneficial effect. CONCLUSIONS Our results show that the combination of insulin and GLP-1 is more effective than insulin or GLP-1 alone in improving endothelial dysfunction, inflammation, and oxidative stress in type 2 diabetes.
- Published
- 2014
21. The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study
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Claudio Franceschi, Michela Cucchi, Maurizio Marra, Massimo Boemi, Antonio Domenico Procopio, Stefano Salvioli, Liana Spazzafumo, Anna Rita Bonfigli, C. Sirolla, Gabriele Brandoni, Roberto Festa, Roberto Testa, Fabiola Olivieri, Antonio Ceriello, Bonfigli A.R., Sirolla C., Testa R., Cucchi M., Spazzafumo L., Salvioli S., Ceriello A., Olivieri F., Festa R., Procopio A.D., Brandoni G., Boemi M., Marra M., and Franceschi C.
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Genotype ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Disease ,p53 polymorphism codon 72 ,Logistic regression ,Polymorphism, Single Nucleotide ,HOMA-IR ,Body Mass Index ,Endocrinology ,Insulin resistance ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Genetic model ,Internal Medicine ,medicine ,Homeostasis ,Humans ,Codon ,Aged ,diabetes mellitu ,business.industry ,Fasting ,General Medicine ,Middle Aged ,medicine.disease ,Lipids ,Cross-Sectional Studies ,type 2 ,Diabetes Mellitus, Type 2 ,Female ,Insulin Resistance ,Tumor Suppressor Protein p53 ,Energy Metabolism ,business ,Body mass index - Abstract
Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin (β = -1.27; p = 0.001) and HOMA-IR (β = -0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.
- Published
- 2012
22. Oscillating glucose induces microRNA-185 and impairs an efficient antioxidant response in human endothelial cells
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Stefano Genovese, Anna Rita Bonfigli, Antonio Ceriello, Valeria De Nigris, Gemma Pujadas, Lucia La Sala, Roberto Testa, and Monica Cattaneo
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Endothelium ,Endocrinology, Diabetes and Metabolism ,Carbohydrate metabolism ,medicine.disease_cause ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,Glutathione Peroxidase GPX1 ,Downregulation and upregulation ,Oscillating glucose ,Internal medicine ,Antioxidant defense ,GPx-1 ,medicine ,Humans ,Luciferase ,Original Investigation ,Glutathione Peroxidase ,Gene knockdown ,Superoxide Dismutase ,business.industry ,Endothelial Cells ,Glutathione ,Catalase ,Cell biology ,miR-185 ,MicroRNAs ,Oxidative Stress ,Glucose ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Immunology ,Cardiology and Cardiovascular Medicine ,business ,Oxidation-Reduction ,Intracellular ,Oxidative stress - Abstract
Background Intracellular antioxidant response to high glucose is mediated by Cu/Mn-superoxide dismutases (SOD-1/SOD-2), catalase (CAT) and glutathione peroxidases (GPx), particularly glutathione peroxidase-1 (GPx-1). Although oscillating glucose can induce a more deleterious effect than high glucose on endothelial cells, the mechanism by which oscillating glucose exerts its dangerous effects is incompletely understood; however, the involvement of oxidative damage has been generally accepted. In this study we sought to determine whether oscillating glucose differentially modulates antioxidant response, and to elucidate the potential regulatory mechanisms exerted by the microRNA-185 (miR-185). Methods Human endothelial cells were exposed for 1 week to constant and oscillating high glucose. SOD-1, SOD-2, CAT and GPx-1, as well as two markers of oxidative stress [8-hydroxy-2′-deoxyguanosine (8-OHdG) and the phosphorylated form of H2AX (γ-H2AX)] were measured at the end of the experiment. Intracellular miR-185 was measured and loss-of function assays were performed in HUVEC. Bioinformatic tool was used to predict the link between miR-185 on 3′UTR of GPx-1 gene. Luciferase assay was performed to confirm the binding on HUVEC. Results After exposure to constant high glucose SOD-1 and GPx-1 increased, while in oscillating glucose SOD-1 increased and GPx-1 did not. SOD-2 and CAT remained unchanged under both conditions. A critical involvement of oscillating glucose-induced miR-185 in the dysregulation of endogenous GPx-1 was found. Computational analyses predict GPx-1 as miR-185′s target. HUVEC cultures were used to confirm glucose’s causal role on the expression of miR-185, its target mRNA and protein and finally the activation of antioxidant response. In vitro luciferase assays confirmed computational predictions targeting of miR-185 on 3′-UTR of GPx-1 mRNA. Knockdown of miR-185, using anti-miR-185 inhibitor, was accompanied by a significant upregulation of GPx-1 in oscillating glucose. 8-OHdG and γ-H2AX increased more in oscillating glucose than in constant high glucose. Conclusions Glucose oscillations may exert more deleterious effects on the endothelium than high glucose, likely due to an impaired response of GPx-1, coupled by the upregulation of miR-185. Electronic supplementary material The online version of this article (doi:10.1186/s12933-016-0390-9) contains supplementary material, which is available to authorized users.
- Published
- 2016
23. Evidence That Hyperglycemia After Recovery From Hypoglycemia Worsens Endothelial Function and Increases Oxidative Stress and Inflammation in Healthy Control Subjects and Subjects With Type 1 Diabetes
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Dario Giugliano, Antonio Ceriello, Emilio Ortega, Gemma Pujadas, Anna Rita Bonfigli, Lucia La Sala, Anna Novials, Roberto Testa, and Katherine Esposito
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Adult ,Male ,medicine.medical_specialty ,Complications ,endocrine system diseases ,Endothelium ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Inflammation ,Ascorbic Acid ,Hypoglycemia ,Antioxidants ,Young Adult ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Endothelial dysfunction ,Infusions, Intravenous ,Type 1 diabetes ,Cross-Over Studies ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Ascorbic acid ,Vasodilation ,Oxidative Stress ,Diabetes Mellitus, Type 1 ,Glucose ,Endocrinology ,medicine.anatomical_structure ,Cardiovascular Diseases ,Hyperglycemia ,Female ,Endothelium, Vascular ,Inflammation Mediators ,medicine.symptom ,business - Abstract
Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia–reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.
- Published
- 2012
24. Leukocyte telomere length is associated with complications of Type 2 diabetes mellitus
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Antonio Ceriello, M. Marra, Liana Spazzafumo, Clara Castellucci, Fabiola Olivieri, Anna Rita Bonfigli, C. Sirolla, Maria Rita Rippo, Roberto Antonicelli, Ivano Testa, Roberto Testa, Claudio Franceschi, and Antonio Domenico Procopio
- Subjects
medicine.medical_specialty ,Cross-sectional study ,business.industry ,Endocrinology, Diabetes and Metabolism ,Type 2 Diabetes Mellitus ,Disease ,Odds ratio ,medicine.disease ,Surgery ,Endocrinology ,Diabetes management ,Predictive value of tests ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Complication ,business - Abstract
Diabet. Med. 28, 1388–1394 (2011) Abstract Objective The key goal of diabetes management is to prevent complications. While the patho-physiological mechanisms responsible for diabetes complications have been extensively studied, at present it is impossible to predict which patient with diabetes could develop complications. In recent years, the role of leukocyte telomere length in the pathogenesis of cardiovascular disease and Type 2 diabetes has been investigated. However, studies aiming to investigate the role of telomeres in the development and progression of Type 2 diabetes, as well as diabetic complications, are still lacking. As a consequence, this study aimed to verify whether leukocyte telomere length is associated with the presence and the number of diabetic complications in a sample of patients with Type 2 diabetes. Methods This is a cross-sectional study. Nine hundred and one subjects were enrolled, including 501 patients with Type 2 diabetes, of whom 284 had at least one complication and 217 were without complications, and 400 control subjects. Leukocyte telomere length was measured by quantitative real-time PCR. Results Patients with diabetes complications had significantly shorter leukocyte telomere length than both patients without diabetes complications and healthy control subjects. Moreover, among patients with diabetes complications, leukocyte telomere length became significantly and gradually shorter with the increasing number of diabetes complications. The magnitude of the effect of the decrease of the abundance of telomeric template vs. a single-copy gene length (T/S ratio) on complications is described by the estimated odds ratio OR = 5.44 (95% CI 3.52–8.42). Conclusions The results of the study support the hypothesis that telomere attrition may be a marker associated with the presence and the number of diabetic complications.
- Published
- 2011
25. In the Light of the Metabolic Memory Theory, Should Not All Aged People with Dysglycemia Be Treated?
- Author
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Ivano Testa, Maurizio Marra, Roberto Testa, and Anna Rita Bonfigli
- Subjects
Blood Glucose ,Aging ,medicine.medical_specialty ,endocrine system diseases ,Longevity ,Models, Biological ,Therapeutic approach ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Intensive care medicine ,Aged ,Successful aging ,business.industry ,nutritional and metabolic diseases ,Memory theory ,medicine.disease ,Clinical Practice ,Knowledge ,Endocrinology ,Hyperglycemia ,High glucose ,Insulin Resistance ,Geriatrics and Gerontology ,business ,Target organ - Abstract
Dysglycemia has been coined to define the prediabetic state. It defines high glucose levels below the diabetes “cut-offs.” The negative effects of dysglycemia, leading to cardiovascular complications, are amplified during aging. Despite this knowledge, treatment of dysglycemia in old subjects is usually overlooked by clinical practice. This article deals with a new theory regarding an intensive therapeutic approach targeting aged people. This hypothesis arises from the recent theory of metabolic memory, which defines early imprinting due to hyperglycemia in cells of the vasculature and of target organs, favoring the development of vascular complications. In addition, metabolic memory determines a durable effect of hypoglycemic treatment that is much longer than the period of therapy. This new evidence could allow us to hypothesize that a treatment of dysglycemia in aged people could remodel their glucose “trajectory” during aging toward a more optimal one, leading to successful aging.
- Published
- 2010
26. Propranolol reduces the response of serum bile acids to oral chenodeoxycholic acid, possibly as a reflex reaction to reduced portal blood flow in healthy and cirrhotic subjects
- Author
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Roberto Testa, F. Dagnino, A. Grasso, and Guido Celle
- Subjects
Male ,medicine.medical_specialty ,Cirrhosis ,medicine.drug_class ,Propranolol ,Chenodeoxycholic Acid ,Gastroenterology ,Bile Acids and Salts ,chemistry.chemical_compound ,Liver Cirrhosis, Alcoholic ,Oral administration ,Chenodeoxycholic acid ,Internal medicine ,medicine ,Humans ,Splanchnic Circulation ,Hepatology ,Bile acid ,Area under the curve ,Middle Aged ,medicine.disease ,Endocrinology ,Intestinal Absorption ,chemistry ,Reflex ,Female ,Splanchnic ,Liver Circulation ,medicine.drug - Abstract
To evaluate if a drug that affects splanchnic and portal flow reduces intestinal bile acid absorption, we studied the effect of propranolol (40 mg oral dose) both on the response of total bile acids (SBA) to oral chenodeoxycholic acid (CDCA 250 mg) and on the estimated hepatic flow by indocyanine green kinetics in 10 healthy and 14 cirrhotic subjects. In 18 subjects who showed a reduction in resting heart rate of almost -5%, propranolol significantly reduced the SBA area under the curve after CDCA in both healthy (mumol/l/h m +/- SD from 181.7 x 144.9 to 56.5 +/- 36.4 p less than 0.02) and cirrhotic (from 1412.1 +/- 1044.8 to 1129.2 +/- 978.8 p less than 0.01) subjects. Variable but not significant modifications were observed in estimated hepatic flow. These results suggest that the propranolol-induced changes in SBA response to CDCA could be a reflex reaction to changes in splanchnic/portal flow.
- Published
- 2008
27. +647 A/C and +1245 MT1A polymorphisms in the susceptibility of diabetes mellitus and cardiovascular complications
- Author
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C. Sirolla, Silvia Tesei, Robertina Giacconi, Elisa Muti, E. Mocchegiani, Anna Rita Bonfigli, Catia Cipriano, M. Marra, Francesco Piacenza, Marco Malavolta, Laura Costarelli, and Roberto Testa
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Disease ,Type 2 diabetes ,Polymorphism, Single Nucleotide ,Biochemistry ,Diabetes Complications ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Genetics ,Humans ,Medicine ,SNP ,Genetic Predisposition to Disease ,Allele ,Molecular Biology ,Aged ,Glycemic ,business.industry ,Middle Aged ,Flow Cytometry ,medicine.disease ,Zinc ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Cohort ,Female ,Metallothionein ,Hemoglobin ,business - Abstract
Diabetes mellitus is a chronic disease characterized by an overproduction of reactive oxygen species, which perturbs zinc metabolism and promotes the onset of cardiovascular disease (CVD) in diabetic patients. Metallothioneins (MT) are cysteine-rich metal-binding proteins which, by means of their antioxidant and zinc-buffering properties, might prevent the development of diabetic cardiovascular complications. A recent investigation shows that a polymorphism (+647 A/C) in the human MT-1A gene, affects the intracellular zinc ion release (iZnR) from the proteins and is associated with longevity in Italian population. The aim of the present study is to assess the involvement of +647 A/C and +1245 A/G MT1A polymorphisms with the susceptibility to type 2 diabetes (DM2) and cardiovascular complications. The study included 694 old individuals: 242 old healthy controls, 217 DM2 patients without clinical evidence of CVD (DNC) and 235 diabetic patients with diagnosis of CVD (DCVD). +647 A/C MT1A polymorphism, but not the second SNP, was associated with DM2. C allele carriers were more prevalent in DNC and DCVD patients than in control group (OR=1.37, p=0.034; OR=1.54, p=0.002, respectively). C+ carriers was associated with higher glycemia and glycosylated hemoglobin in DCVD patients, but not in DNC or control subjects. No differences in plasma zinc, but a modulation of MT levels and iZnR in PBMCs were observed in DCVD cohort when related to +647 A/C MT1A polymorphism. In summary, this work provides novel evidence on the association of the +647 A/C MT1A polymorphism with DM2. Moreover, C+ carriers in DCVD patients presented a worse glycemic control, a reduced iZnR and a higher MT levels, suggesting a possible role of MT in diabetic cardiovascular complications.
- Published
- 2008
28. C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position −675 of the PAI-1 gene
- Author
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Antonio Ceriello, M. Marra, Antonio Procopio, E. Sacchi, Anna Rita Bonfigli, Massimo Boemi, Roberto Testa, Alberto Dolci, A. Catalano, Daniela Mari, and C. Sirolla
- Subjects
Male ,medicine.medical_specialty ,Genotype ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Population ,Medicine (miscellaneous) ,Type 2 diabetes ,Polymerase Chain Reaction ,Antigen ,Polymorphism (computer science) ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Fibrinolysis ,medicine ,Humans ,Allele ,Promoter Regions, Genetic ,education ,education.field_of_study ,Polymorphism, Genetic ,Nutrition and Dietetics ,biology ,business.industry ,C-reactive protein ,Middle Aged ,medicine.disease ,In vitro ,C-Reactive Protein ,Endocrinology ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Immunology ,biology.protein ,Regression Analysis ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
C-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. "In vitro" studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications.Two hundred and ninety-five type 2 diabetic patients (age 60.9+/-10.5 years) and 290 healthy controls (age 59.2+/-11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r=0.45, p0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r=0.31, p0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r=0.64 p0.001) and 4G/5G (partial r=0.47, p0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r=0.45, p0.001) and in 4G/5G (partial r=0.34, p=0.007) diabetic patients.These findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.
- Published
- 2008
29. An open population screening study for HFE gene major mutations proves the low prevalence of C282Y mutation in Central Italy
- Author
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O. Di Andrea, Daniela Basso, E. Rosa Rizzotto, Filippo Navaglia, Maria Chiaramonte, Annarosa Floreani, Vincenzo Baldo, Roberto Testa, Martina Zaninotto, I. Petridis, and Maurizio Marra
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Mutation ,medicine.medical_specialty ,Pathology ,Hepatology ,biology ,business.industry ,Transferrin saturation ,Gastroenterology ,nutritional and metabolic diseases ,medicine.disease ,medicine.disease_cause ,Major gene ,Ferritin ,Internal medicine ,medicine ,biology.protein ,Population study ,Pharmacology (medical) ,Steatosis ,business ,Allele frequency ,Body mass index - Abstract
Summary Background The C282Y mutation in the HFE gene is responsible for most cases of hereditary haemochromatosis. Aim To investigate the allele frequency of HFE mutations and the associations between mutations and cases of iron overload or liver diseases in an open population of Central Italy. Methods A total of 502 individuals over 8 years of age, comprising 203 males and 299 females, who were residents in Arsita (a small town in Central Italy), were assayed for: C282Y, H63D and S65C mutations of the HFE gene by TaqMan probes; body mass index, serum ferritin, transferrin saturation, transaminases, GGT, glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, HBV and HCV serum markers. Information was obtained on alcohol intake. Liver ultrasound was performed in 334 (67%) subjects. Results The allele frequencies for C282Y, H63D and S65C were 2%, 15%, and 0.01%, respectively. C282Y/wt was found in 19 subjects (4%), H63D/wt in 127 (25%), H63D/H63D in 11 (2%) and S65C/wt in one (2.0‰). No homozygosity for C282Y or compound mutation (C282Y/H63D) was found in the study population, but 27 subjects (5%) had TfSat >45% (including 10 subjects with high serum ferritin). Overall, 49 subjects (9.8%) were HCV-RNA-positive. Logistic regression analysis indicated that male gender (P = 0.000) and hepatic steatosis (P = 0.017) were independent variables correlating to a high serum ferritin. Conclusion C282Y HFE mutation is less frequent in Central Italy than in Northern Italy.
- Published
- 2007
30. MiR-21-5p and miR-126a-3p levels in plasma and circulating angiogenic cells: relationship with type 2 diabetes complications
- Author
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Luigina Micolucci, Anna Rita Bonfigli, Roberto Testa, Antonio Domenico Procopio, Francesco Prattichizzo, Emanuela Mensà, Fiorella Marcheselli, Fabiola Olivieri, Liana Spazzafumo, Raffaella Lazzarini, Massimiliano Bonafè, Mirko Gobbi, Massimo Boemi, Rina Recchioni, Roberto Antonicelli, Gabriele Santini, Angelica Giuliani, Olivieri, Fabiola, Spazzafumo, Liana, Bonafè, Massimiliano, Recchioni, Rina, Prattichizzo, Francesco, Marcheselli, Fiorella, Micolucci, Luigina, Mensà, Emanuela, Giuliani, Angelica, Santini, Gabriele, Gobbi, Mirko, Lazzarini, Raffaella, Boemi, Massimo, Testa, Roberto, Antonicelli, Roberto, Procopio, Antonio Domenico, and Bonfigli, Anna Rita
- Subjects
Male ,medicine.medical_specialty ,endocrine system diseases ,Inflammation ,diabetes complication ,Type 2 diabetes ,Gastroenterology ,Proinflammatory cytokine ,Diabetes Complications ,Research Paper: Gerotarget (Focus on Aging) ,Internal medicine ,microRNA ,medicine ,Mir 21 5p ,circulating miRNAs ,Humans ,cardiovascular diseases ,Aged ,Diabetes Complication ,business.industry ,Gerotarget ,Healthy subjects ,nutritional and metabolic diseases ,Middle Aged ,miR-126 ,medicine.disease ,circulating miRNA ,MicroRNAs ,Oncology ,Female ,Endothelium, Vascular ,miR-21 ,type 2 diabetes ,medicine.symptom ,business ,Biomarkers ,Mace - Abstract
Innovative biomarkers are required to manage type 2 diabetic patients (T2DM). We focused our study on miR-126-3p and miR-21-5p levels, as biomarkers of endothelial function and inflammation. MiRNAs levels were measured in plasma from 107 healthy subjects (CTR) and 193 diabetic patients (T2DM), 76 without (T2DM NC) and 117 with (T2DM C) complications. When diabetic complication were analysed as a whole, miR-126-3p and miR-21-5p levels declined significantly from CTR to T2DM NC and T2DM C patients. When miRNAs levels were related to specific complications, significantly higher miR-21-5p levels (0.46 ± 0.44 vs. 0.26 ± 0.33, p < 0.001) and significant lower miR-126-3p levels (0.21 ± 0.21 vs. 0.28 ± 0.22, p = 0.032) were found in T2DM with previous major cardiovascular events (MACE) vs. all the others T2DM patients. To confirm these results we focused on circulating angiogenic cells (CACs) from a subgroup of 10 CTR, 15 T2DM NC and 15 T2DM patients with MACE. CACs from T2DM patients expressed higher miR-21-5p and lower miR-126-3p levels than CACs from CTR. Furthermore, CACs from T2DM + MACE showed the highest levels of miR-21-5p. Circulating miR-21-5p and miR-126-3p emerge as dynamic biomarkers of systemic inflammatory/angiogenic status. Their expression levels in CACs from T2DM with MACE suggest a shift from a proangiogenic to a proinflammatory profile.
- Published
- 2015
31. Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C: role of platelet count/spleen diameter ratio index
- Author
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Luis Isola, S. Milazzo, Emanuela Testa, Roberto Testa, Paolo Borro, Domenico Risso, Edoardo G. Giannini, P. B. Lantieri, and P. Ceppa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Concordance ,Gastroenterology ,Statistics, Nonparametric ,Liver Function Tests ,Fibrosis ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Platelet ,Aminopyrine ,Ultrasonography ,Breath test ,medicine.diagnostic_test ,Platelet Count ,business.industry ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Breath Tests ,Liver ,ROC Curve ,Female ,Liver function ,business ,Hepatic fibrosis ,Liver function tests ,Body mass index ,Biomarkers ,Spleen - Abstract
Objectives. Noninvasive evaluation of fibrosis is an on-going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging. Design. We evaluated the biochemical, functional [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic hepatitis C patients. Results. Clinical [body mass index (BMI)], biochemical [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT)] and ratio indexes, together with the ABT, showed a higher relationship with fibrosis: initial (score ≤ 2) versus evident (score > 2) fibrosis: BMI (24 ± 2 vs. 26 ± 2, P = 0.0007), AST (56 ± 36 vs. 88 ± 65, P = 0.0159), ALT (92 ± 54 vs. 139 ± 108, P = 0.0290), PLT (220 ± 64 vs. 173 ± 61, P = 0.0007), PLT/spleen diameter ratio (PLT/SPD) (2133 ± 786 vs. 1540 ± 681, P = 0.0003), AST/platelet count ratio index (APRI) (0.80 ± 0.87 vs. 1.51 ± 1.47, P = 0.0010), ABT%d/h30 min (10.8 ± 4.5 vs. 7.6 ± 3.8, P = 0.0007), ABT%d/cum120 min (8.9 ± 3.3 vs. 6.5 ± 3.1, P = 0.0007). Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and PLT/SPD ratio proved to be statistically significant. Multivariate stepwise analysis (with and without BMI) identified two models for distinguishing between initial and evident fibrosis: Model 1: −0.569 +(BMI × 0.107) + (APRI × 0.169)−(PLT/SPD × 0.304), and Model 2: 2.376 + (APRI × 0.152)−(ABTd/h30 × 0.043)−(PLT/SPD × 0.249). These models showed concordance in identifying or ruling out evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio also showed 78.7% concordance with the histological score. Conclusion. These results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C may be considered an effective tool thanks to the use of an inexpensive, reproducible ratio index.
- Published
- 2006
32. Can Helicobacter pylori Eradication Regimens be Shortened in Clinical Practice? An Open-label, Randomized, Pilot Study of 4 and 7-day Triple Therapy With Rabeprazole, High-dose Levofloxacin, and Tinidazole
- Author
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C. Bilardi, Mario Mamone, Roberto Testa, Maria L. Santi, Vincenzo Savarino, Pietro Dulbecco, Edoardo G. Giannini, and Carlo Mansi
- Subjects
Ofloxacin ,medicine.medical_specialty ,medicine.drug_class ,Rabeprazole ,Proton-pump inhibitor ,Antitrichomonal Agents ,Pilot Projects ,Levofloxacin ,macromolecular substances ,Gastroenterology ,2-Pyridinylmethylsulfinylbenzimidazoles ,Drug Administration Schedule ,Tinidazole ,Helicobacter Infections ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Humans ,Medicine ,Omeprazole ,Antibacterial agent ,Dose-Response Relationship, Drug ,Helicobacter pylori ,biology ,business.industry ,Anti-Ulcer Agents ,biology.organism_classification ,Anti-Bacterial Agents ,Surgery ,Treatment Outcome ,Breath Tests ,Benzimidazoles ,Drug Therapy, Combination ,business ,medicine.drug - Abstract
Background: Rabeprazole is a proton pump inhibitor which is particularly suitable for use in short-term Helicohacter pylori eradication treatment. Levofloxacin-based H. pylori eradication regimens have shown good efficacy and very few side effects. Shorter treatment and absence of significant side effects should improve compliance to therapy and increase the Hp H. pylori eradication rate. Aims: To evaluate the effectiveness of 2 rabeprazole-based H. pylori eradication regimens in an open-label, randomized study carried out in a clinical practice setting. Methods: One hundred sixty-nine consecutive, treatment-naive patients with H. pylori infection were randomized to receive rabeprazole (20 mg, bid), levofloxacin (500 mg, bid), and tinidazole (500 mg, bid) for either 4 [4-d rabeprazole, levofloxacin, tinidazole (RLT), n = 85] or 7 days (7-d RLT, n = 84). Before treatment, all patients underwent upper digestive endoscopy. Cure rates were assessed by means of 13 C-urea breath test. and were compared with the eradication rate obtained with standard triple therapy in our Unit (ie, 78%) and average eradication rate reported in the literature (ie, 79%). Results: The intention-to-treat eradication rates were 94% [87% to 98%, 95% confidence interval (CI)] and 95% (88% to 99%, 95% CI) in the 4-day RLT and 7-day RLT regimens, respectively, whereas per-protocol eradication rates were 95% (88% to 99%, 95% CI) in the 4-day RLT and 96% (90% to 99%, 95% CI) in the 7-day RLT. Both treatment regimens obtained significantly higher eradication rates as compared with standard triple therapy. The 4-day RLT showed significantly fewer side effects. Conclusions: In a clinical practice setting, both 4-day and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens achieved relevant H. pylori eradication rates in treatment-naive patients. The lower number of side effects makes the shorter treatment regimen preferable over the conventional 7-day treatment.
- Published
- 2006
33. A Simple Approach to Noninvasively Identifying Significant Fibrosis in Chronic Hepatitis C Patients in Clinical Practice
- Author
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Roberto Testa, Luca Mastracci, Domenico Risso, Edoardo G. Giannini, Paola Ceppa, and Atif Zaman
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,digestive system ,Gastroenterology ,Liver Function Tests ,Chronic hepatitis ,Predictive Value of Tests ,Fibrosis ,Internal medicine ,medicine ,Humans ,Platelet ,Aspartate Aminotransferases ,Retrospective Studies ,medicine.diagnostic_test ,Receiver operating characteristic ,Platelet Count ,business.industry ,Reproducibility of Results ,Alanine Transaminase ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,digestive system diseases ,Clinical Practice ,ROC Curve ,Liver biopsy ,Female ,business ,Algorithms ,Biomarkers ,Significant fibrosis - Abstract
Background Identification of the presence of significant fibrosis is an important part of the diagnostic work-up of patients with chronic hepatitis C (CHC). Aim To evaluate the performance of the aspartate to alanine aminotransferase ratio (AST/ALT ratio) and platelet count in reducing the number of liver biopsies and diagnosing the presence/absence of significant fibrosis in a large cohort of patients with CHC seen at 2 tertiary referral centers. Methods Liver biopsies of 409 patients with CHC were evaluated. Staging was carried out by means of the Ishak and METAVIR scores in the Italian and US series, respectively. Prevalence of significant fibrosis was 43%. Receiver operating characteristic curves were used to identify AST/ALT ratio and platelet count cutoffs with the highest accuracy for the diagnosis of significant fibrosis. These cutoffs were used to devise a diagnostic algorithm for reducing the number of liver biopsies and diagnosing/ruling out significant fibrosis. Results AST/ALT ratios increased and platelet counts decreased as liver fibrosis worsened. Both AST/ALT ratio (c-index=0.747) and platelet count (c-index=0.733) had high accuracy for the diagnosis of significant fibrosis. The use of AST/ALT ratio and platelet count cutoffs in a diagnostic algorithm would have avoided liver biopsy in 68.9% of the patients and would have correctly identified the absence/presence of significant fibrosis in 80.5% of these cases. Conclusions In clinical practice, the use of simple, reproducible, and inexpensive parameters such as the AST/ALT ratio and platelet count can reduce the need for liver biopsy in a substantial proportion of patients with CHC.
- Published
- 2006
34. Hyaluronic acid and aspartate aminotransferase levels normalized by liver function can reflect sinusoidal impairment in chronic liver disease
- Author
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Cinzia Cordiviola, Domenico Risso, Edoardo G. Giannini, Sara Milazzo, Tiziana Cotellessa, Federica Malfatti, Elisa Marabotto, Emanuela Testa, Mario Mamone, Paola Ceppa, and Roberto Testa
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Biopsy ,Chronic liver disease ,Gastroenterology ,chemistry.chemical_compound ,Model for End-Stage Liver Disease ,Fibrosis ,Internal medicine ,Hyaluronic acid ,medicine ,Humans ,Aspartate Aminotransferases ,Endothelium ,Liver damage ,Hyaluronic Acid ,Aminopyrine ,Breath test ,Hepatology ,medicine.diagnostic_test ,business.industry ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Breath Tests ,Liver ,chemistry ,Disease Progression ,Female ,Liver function ,business ,Biomarkers - Abstract
Background/Aim: To evaluate the relationship between hyaluronic acid/aminopyrine breath test (HA/ABT) ratio and fibrosis score in chronic hepatitis, and between HA/ABT and clinical staging (child-turcotte-pugh'score, CTP; and model for end stage liver disease, MELD) in cirrhosis, as well as to evaluate the aspartate aminotransferase (AST)/ABT in relation to the HA/ABT. Methods: We studied 48 patients with histologically proven chronic hepatitis C (CHC) and 35 patients with compensated cirrhosis (CIR). Results: HA/ABT and AST/ABT showed a more significant correlation with the fibrosis score than HA or ABT or AST alone in the 48 CHC patients: r=0.568 (P
- Published
- 2006
35. A study of 4- and 7-day triple therapy with rabeprazole, high-dose levofloxacin and tinidazole rescue treatment for Helicobacter pylori eradication
- Author
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Mario Mamone, Pietro Dulbecco, Roberto Testa, C. Bilardi, Vincenzo Savarino, M. L. Santi, Carlo Mansi, and Edoardo G. Giannini
- Subjects
Male ,Ofloxacin ,medicine.medical_specialty ,Time Factors ,Rabeprazole ,Antitrichomonal Agents ,Pilot Projects ,Levofloxacin ,Gastroenterology ,2-Pyridinylmethylsulfinylbenzimidazoles ,Drug Administration Schedule ,Tinidazole ,Helicobacter Infections ,law.invention ,Pharmacotherapy ,Anti-Infective Agents ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Enzyme Inhibitors ,Antibacterial agent ,Breath test ,Helicobacter pylori ,Hepatology ,medicine.diagnostic_test ,biology ,business.industry ,Middle Aged ,biology.organism_classification ,Anti-Bacterial Agents ,Surgery ,Treatment Outcome ,Benzimidazoles ,Drug Therapy, Combination ,Female ,business ,Omeprazole ,medicine.drug - Abstract
Summary Background Helicobacter pylori treatment failure is becoming an emergent problem in clinical practice. Shorter treatment duration should improve compliance to therapy and keep an acceptable H. pylori eradication rate. Aims To evaluate the efficacy of two rabeprazole, high-dose levofloxacin and tinidazole-based regimens as ‘rescue’ treatment for H. pylori eradication in an open-label, randomized, pilot study carried out in a clinical practice setting. Methods Eighty-five consecutive patients who have previously failed at least one H. pylori eradication attempt were randomized to receive rabeprazole (20 mg, b.d.), levofloxacin (500 mg, b.d.) and tinidazole (500 mg, b.d.) either for 4 (4-day RLT, n = 42) or 7 days (7-day RLT, n = 43). Cure of H. pylori infection was assessed by means of 13C-urea breath test. Results The 7-day RLT achieved 84% (95% CI: 69–93%) and 86% (95% CI: 72–95%) eradication rates in intention-to-treat and per-protocol analyses respectively. The shorter treatment obtained an 83% (95% CI: 69–93%) eradication rate in both intention-to-treat and per-protocol analysis. Both regimens were well tolerated, although patients who received the 4-day RLT reported fewer side-effects. Conclusions In patients who have previously failed at least one H. pylori eradication attempt, both 4- and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens are effective in curing the infection in more than 80% of patients.
- Published
- 2006
36. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients
- Author
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Gabriella Andraghetti, Federica Malfatti, Chiara Mazzucchelli, A. Grasso, Antonino Picciotto, Sara Labanca, Renzo Cordera, Simona Marenco, and Roberto Testa
- Subjects
medicine.medical_specialty ,Article Subject ,Virus ,chemistry.chemical_compound ,Insulin resistance ,Internal medicine ,Genotype ,medicine ,lcsh:RC799-869 ,Hepatology ,business.industry ,Ribavirin ,Leptin ,Confounding ,Gastroenterology ,nutritional and metabolic diseases ,virus diseases ,medicine.disease ,Endocrinology ,chemistry ,Serum leptin ,lcsh:Diseases of the digestive system. Gastroenterology ,business ,Viral load ,Research Article - Abstract
Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders.Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment.Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR.Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.
- Published
- 2014
37. Influence of 1-Week Helicobacter pylori Eradication Therapy with Rabeprazole, Clarithromycin, and Metronidazole on 13C-Aminopyrine Breath Test
- Author
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Federica Malfatti, Edoardo G. Giannini, Emanuela Testa, Federica Botta, Mario Mamone, Simone Polegato, Roberto Testa, Alessandra Fumagalli, and Vincenzo Savarino
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Population ,Rabeprazole ,Pharmacology ,Gastroenterology ,2-Pyridinylmethylsulfinylbenzimidazoles ,Helicobacter Infections ,Anti-Infective Agents ,Cytochrome P-450 Enzyme System ,Liver Function Tests ,Clarithromycin ,Metronidazole ,Internal medicine ,medicine ,Humans ,Drug Interactions ,Enzyme Inhibitors ,Aminopyrine ,education ,Aged ,Antibacterial agent ,Breath test ,Carbon Isotopes ,education.field_of_study ,Helicobacter pylori ,medicine.diagnostic_test ,biology ,Chemistry ,Middle Aged ,biology.organism_classification ,Anti-Bacterial Agents ,Breath Tests ,Liver ,Benzimidazoles ,Drug Therapy, Combination ,Female ,Liver function ,Omeprazole ,medicine.drug - Abstract
Helicobacter pylori eradication therapy is commonly prescribed in the general population. Treatment consists of drugs that are mainly metabolized by the liver cytochrome P-450 (CYP) enzymatic pool. Most H. pylori-infected patients often take drugs for comorbid illnesses, therefore increasing the potential for drug-drug interactions. We aimed to evaluate the interactions of rabeprazole, clarithromycin, and metronidazole 1-week H. pylori eradication therapy with CYP-dependent liver metabolic function in clinical practice. Ten patients referred to our unit for H. pylori infection underwent 1-week eradication therapy with rabeprazole (20 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and metronidazole (500 mg, b.i.d.). We chose the 13C-aminopyrine breath test (13C-ABT) to evaluate CYP-dependent liver function since it is noninvasive and nonharmful. All patients underwent 13C-ABT at three time points: before therapy (to), at the end of therapy (t8), and after 1 month of follow-up (t38). Mean 13C-ABT dose/hr (t0 = 14.0 +/- 5.4, t8 = 13.5 +/- 4.0, t38 = 16.1 +/- 5.6) as well as 13C-ABT cumulative dose (t0 = 2.4 +/- 1.1, t8 = 2.4 +/- 0.8, t38 = 2.6 +/- 1.0) were not statistically different at the three time points of the study. These results did not seem to be influenced by drugs being administered concomitantly. In everyday clinical practice rabeprazole-based H. pylori eradication therapy does not seem to display any significant interactions with CYP-dependent liver function, even in patients on multiple drugs.
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- 2005
38. C-galactose breath test and C-aminopyrine breath test for the study of liver function in chronic liver disease
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Roberto Testa, Alessandra Fumagalli, Federica Botta, Domenico Risso, Edoardo G. Giannini, Tiziana Cotellessa, Federica Malfatti, Emanuela Testa, Simone Polegato, Paolo Borro, Alberto Fasoli, and Sara Milazzo
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Breath test ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Gold standard (test) ,medicine.disease ,Chronic liver disease ,Surgery ,Liver biopsy ,Internal medicine ,medicine ,Etiology ,In patient ,Liver function ,business - Abstract
Background & Aims: Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13C-aminopyrine breath test (13C-ABT) and 13C-galactose breath test (13C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease. Methods: We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13C-GBT and 13C-ABT, and the results were expressed as a percentage of the administered dose of 13C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis. Results: On average, 13C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13C-ABT results from 30 to 120 minutes. 13C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13C-GBT and 13C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis. Conclusions: In patients with chronic liver disease, both 13C-GBT and 13C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.
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- 2005
39. Trans-catheter arterial chemoembolisation for hepatocellular carcinoma in patients with viral cirrhosis: role of combined staging systems, Cancer Liver Italian Program (CLIP) and Model for End-stage Liver Disease (MELD), in predicting outcome after treatm
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Edoardo G. Giannini, Domenico Risso, Simone Polegato, Bruno Chiarbonello, Alessandra Fumagalli, Elena Podestà, G. De Caro, Emanuela Testa, Paola Romagnoli, Roberto Testa, Federica Botta, Federica Malfatti, and G. Cittadini
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Palliative care ,Gastroenterology ,Liver disease ,Model for End-Stage Liver Disease ,Internal medicine ,medicine ,Carcinoma ,Humans ,Pharmacology (medical) ,Chemoembolization, Therapeutic ,Survival analysis ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Hepatology ,business.industry ,Liver Neoplasms ,Palliative Care ,Cancer ,Middle Aged ,medicine.disease ,Survival Analysis ,body regions ,Treatment Outcome ,Hepatocellular carcinoma ,Female ,business ,Liver Failure - Abstract
Summary Background: Trans-catheter arterial chemoembolisation (TACE) is the most common palliative treatment for hepatocellular carcinoma (HCC). The therapeutic options depend both on the characteristics of the tumour and on functional staging of the cirrhosis. Aim: To evaluate the effects of TACE on the survival of cirrhotic patients with HCC according to different staging systems [Okuda score, Cancer Liver Italian Program (CLIP) score, Model for End-stage Liver Disease (MELD) score] and in relation to the side-effects of TACE. Methods: Fifty cirrhotic patients, 36 CTP class A and 14 class B, underwent 106 TACE treatments with mitoxantrone. Survival at 12, 24, and 36 months was evaluated. Results: MELD at 12 months and CLIP at 24 months were identified as significant variables associated with survival. Combined cut-offs of CLIP and of MELD identified four subgroups of patients with different survivals, at 12, 24 and 36 months, respectively: CLIP ≥ 2 and MELD ≥ 10 (63%, 20% and 0%), CLIP
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- 2003
40. Apolipoprotein E polymorphisms and mortality in Italian Type 2 diabetic patients
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F Gregorio, Gabriele Brandoni, C. Sirolla, Richard W. James, P. Fumelli, Roberto Testa, and Massimo Boemi
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Apolipoprotein E ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Clinical Biochemistry ,Population ,General Medicine ,Diabetic angiopathy ,medicine.disease ,Biochemistry ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Diabetes mellitus ,medicine ,Glycated hemoglobin ,education ,business ,Survival analysis ,Lipoprotein ,Cause of death - Abstract
Aims To determine if apolipoprotein E polymorphism is associated with cardiovascular or all-cause mortality in Italian Type 2 diabetic patients. Methods A prospective study of mortality in Type 2 diabetic patients (n = 433) as a function of apolipoprotein E phenotype, which was assessed at entry into the study. During follow up (10 years), 110 (25·4%) patients died of which 66 (15·2%) were the result of cardiovascular causes. Cause of death was established from death certificates and clinical records. The clinical status of the survivors was determined at the end of the study. Results Apolipoprotein E polymorphisms were not associated with excess cardiovascular or all-cause mortality in the Italian Type 2 diabetic patients either in univariate or multivariate analyses. Age, duration of diabetes and glycated haemoglobin levels at entry were the primary determinants of premature mortality in the diabetic population. Conclusions Apolipoprotein E polymorphisms are not markers for premature mortality in Italian Type 2 diabetic patients. The impact of apolipoprotein E mutations may be attenuated by environmental factors, notably a healthier diet, in Italian patients.
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- 2003
41. [Untitled]
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Bruno Chiarbonello, Paola Romagnoli, Roberto Testa, Federica Botta, Vincenzo Savarino, Federica Malfatti, Edoardo G. Giannini, Alberto Fasoli, and Mario Mamone
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medicine.medical_specialty ,Gastric Infection ,Cirrhosis ,biology ,medicine.diagnostic_test ,Physiology ,Gastroenterology ,Hepatitis C ,Hepatology ,Helicobacter pylori ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Liver disease ,Internal medicine ,Immunology ,medicine ,Helicobacter ,Liver function tests - Abstract
Helicobacter pylori gastric infection has been associated with various digestive and extradigestive diseases. In liver disease bacterial infections have been associated with impairment of cytochrome P-450 liver metabolic activity. Moreover, infection by Helicobacter spp. seems to be linked with the development of hepatocellular carcinoma (HCC) in mice. Our aims were to evaluate the influence of H. pylori infection on cytochrome P-450 liver metabolic activity as assessed by means of monoethylglycinexylidide (MEGX) test and to assess the prevalence of H. pylori infection in patients with HCC. Ninety-six hepatitis C virus (HCV) -positive cirrhotic patients, 36 of whom had HCC, were tested for H. pylori infection by means of anti-H. pylori IgG. Patients underwent the MEGX test. Characteristics of the patients were then analyzed on the basis of the presence of H. pylori infection. Seroprevalence of H. pylori infection was similar between cirrhotic patients without (68%) or with (63.8%) HCC. Mean MEGX values were significantly (P < 0.0001) lower in H. pylori infected patients (18.2 +/- 13.9 ng/ml) as compared to the noninfected ones (46.9 +/- 17.1 ng/ml), independently of Child-Pugh's classification. These differences persisted even after subdividing patients according to the presence of HCC. In conclusion, in anti-HCV positive cirrhotic patients H. pylori infection is associated to an impairment of cytochrome P-450 liver metabolic activity. Seroprevalence of H. pylori infection in HCC patients is similar to that observed in tumor-free cirrhotics.
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- 2003
42. Time Is Glucose, Can't Miss Gestational Diabetes
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Mariarosa Carta, Antonio Ceriello, Roberto Festa, and Roberto Testa
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Adult ,Blood Glucose ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Guidelines as Topic ,Glucose testing ,Endocrinology ,Pregnancy ,Diabetes mellitus ,Internal medicine ,Blood plasma ,Humans ,Medicine ,business.industry ,Obstetrics ,nutritional and metabolic diseases ,Prenatal Care ,Fasting ,Gold standard (test) ,Glucose Tolerance Test ,medicine.disease ,Gestational diabetes ,Diabetes, Gestational ,Medical Laboratory Technology ,First trimester ,Diabetes Mellitus, Type 2 ,Gestation ,Female ,Initial prenatal visit ,business - Abstract
Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes, if not treated. International guidelines recommend screening "all or high-risk women" at the initial prenatal visit, when a fasting plasma glucose (FPG) between 92 and 126 mg/dL is diagnostic for GDM. However, glucose testing may be affected by a great pre-analytical variability (usually overlooked), due to, for example, kind of sample (serum/plasma), temperature of storage, time between blood draw and centrifugation (in-tube glycolysis), and use of a glycolysis inhibitor. So GDM may be easily missed. We aimed to evaluate the potential characteristics of this important issue.FPG was tested by both "routine" and "gold standard" protocols in 60 women at the first trimester of gestation, presenting for GDM screening. "Routine" blood plasma was collected in a tube with sodium fluoride, kept at room temperature, centrifuged, and tested 30-45 min after blood draw. "Gold standard" was a specimen from the same blood sample that was centrifuged within 5 min and tested together with the "routine" specimen.In the "routine" protocol, 10 mg/dL on average was lost for each determination. Thirteen cases of GDM and two of overt diabetes (FPG126 mg/dL) were missed in this preliminary series.The risk for GDM underdiagnosis in the first half of pregnancy appears to be actual and wide. A closer collaboration between clinicians and pathologists is critical, allowing a stricter adherence to the laboratory guidelines to be ensured.
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- 2012
43. Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina
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Silvio Fedele, Roberto Testa, Mario Marzilli, and Gianmario Sambuceti
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Abciximab ,Platelet Glycoprotein GPIIb-IIIa Complex ,Immunoglobulin Fab Fragments ,Internal medicine ,Angioplasty ,Coronary Circulation ,Hyperventilation ,Medicine ,Humans ,Platelet ,Angina, Unstable ,Angioplasty, Balloon, Coronary ,Cardiac catheterization ,Aged ,business.industry ,Unstable angina ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Blockade ,medicine.anatomical_structure ,Treatment Outcome ,Anesthesia ,Vascular resistance ,Cardiology ,Female ,Stents ,Vascular Resistance ,medicine.symptom ,business ,Cardiology and Cardiovascular Medicine ,Blood Flow Velocity ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
ObjectivesWe designed a study to explore the effect of glycoprotein (GP) IIb/IIIa blockade on the atherosclerotic plaque and distal coronary vasculature.BackgroundPlatelet GP IIb/IIIa blockers have been proven to be beneficial in acute ischemic syndromes. This effect has also been attributed to the prevention of microvascular obstruction, although the underlying mechanisms have not been fully defined.MethodsEighteen patients with unstable refractory angina pectoris underwent cardiac catheterization and angioplasty. Trans-stenotic and microvascular resistances to flow were measured at baseline, during hyperventilation, and after intracoronary adenosine. Measurements were repeated early after abciximab administration and after successful percutaneous transluminal coronary angioplasty.ResultsHyperventilation induced an ischemic attack in 12 of 18 patients and increased epicardial (12.8 ± 16.9 vs. 6.1 ± 6.1 mm Hg/ml per min, p < 0.05) and microvascular (9.9 ± 7.5 vs. 6.8 ± 5.8 mm Hg/ml per min, p < 0.05) coronary resistance. Abciximab had no significant effect on epicardial resistance, although it significantly reduced distal coronary resistance under all study conditions, including baseline (4.8 ± 4.8 mm Hg/ml per min, p < 0.01), hyperventilation (5.1 ± 5.4 mm Hg/ml per min, p < 0.01), and intracoronary adenosine (2.7 ± 3.0 vs. 4.3 ± 4.3 mm Hg/ml per min, p < 0.05). The hyperventilation test became negative in all patients after abciximab administration.ConclusionsThese observations confirm the immediate beneficial effects of platelet GP IIb/IIIa blockade with abciximab in acute ischemic syndromes and suggest that improvement of microvascular function may play a central role in the mechanism of action of this drug.
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- 2002
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44. Serum thrombopoietin levels are linked to liver function in untreated patients with hepatitis C virus-related chronic hepatitis
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Paola Romagnoli, Emanuela Testa, Edoardo G. Giannini, Paolo Borro, Mario Mamone, Roberto Testa, Simone Polegato, Federica Botta, Alessandra Fumagalli, Federica Malfatti, Bruno Chiarbonello, and Elena Podestà
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Hepatitis C virus ,medicine.disease_cause ,Gastroenterology ,Pathogenesis ,Necrosis ,Fibrosis ,Internal medicine ,Humans ,Medicine ,Aminopyrine ,Thrombopoietin ,Breath test ,Carbon Isotopes ,Hepatology ,medicine.diagnostic_test ,Platelet Count ,business.industry ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Thrombocytopenia ,Breath Tests ,Liver ,Liver biopsy ,Immunology ,Female ,Liver function ,business ,Spleen - Abstract
Thrombocytopenia can be found in patients with chronic hepatitis related to hepatitis C virus (HCV). Both hypersplenism and decreased liver production of thrombopoietin (TPO) have been hypothesized as mechanisms responsible for thrombocytopenia.To assess the presence of relationships among platelet count, spleen size, TPO serum levels, liver histology, and liver function in a group of patients with HCV-related chronic hepatitis.Platelet count, TPO serum levels, and spleen size were assessed in 25 untreated HCV positive chronic hepatitis patients undergoing liver biopsy. These parameters were correlated to liver histology and liver function as evaluated by means of [(13)C]aminopyrine breath test (ABT).Both platelet counts (146 +/- 48 vs. 202 +/- 56 x 10(9)/1, P0.03) and TPO serum levels (103 +/- 24 vs. 158 +/- 7 1 pg/ml, P0.02) were lower among patients with high fibrosis scores as compared to patients with low fibrosis scores. Patients with thrombocytopenia as well as patients with high fibrosis scores had lower ABT results as compared to patients with normal platelet counts and patients with no or mild fibrosis, respectively. TPO serum levels were correlated to platelet count (r(s) = 0.493, P = 0.016), and negatively correlated to fibrosis stage (r(s) = -0.545, P = 0.008). Lastly, low TPO serum levels were associated to a decrease in liver function.Our study showed that in patients with chronic hepatitis related to HCV infection serum TPO levels are correlated to liver functional impairment and to the degree of liver fibrosis.
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- 2002
45. 13 C-Aminopyrine breath test to evaluate severity of disease in patients with chronic hepatitis C virus infection
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Edoardo G. Giannini, Roberto Testa, Simone Polegato, Alberto Fasoli, Bruno Chiarbonello, Emanuela Testa, Federica Botta, Federica Malfatti, Paola Romagnoli, and Alessandra Fumagalli
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Breath test ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,medicine.diagnostic_test ,biology ,business.industry ,Hepatitis C virus ,Hepacivirus ,Gastroenterology ,Hepatitis C ,Chronic liver disease ,medicine.disease ,medicine.disease_cause ,biology.organism_classification ,Surgery ,Internal medicine ,medicine ,Pharmacology (medical) ,Liver function ,business - Abstract
Background: There are few data on the use of the 13C-aminopyrine breath test to evaluate the severity of disease in patients with hepatitis C virus-related chronic liver disease, although these patients represent one of the most important problems in clinical hepatology. Aims: To compare 13C-aminopyrine breath test results of patients with hepatitis C virus-related chronic hepatitis and Child–Pugh class A cirrhosis with those of normal subjects, and to evaluate different methods of expressing 13C-aminopyrine breath test results. Methods: Twenty-four patients with hepatitis C virus-related chronic hepatitis and 17 patients with Child–Pugh class A cirrhosis underwent 13C-aminopyrine breath test. Breath samples were collected every 30 min up to 2 h after 13C-aminopyrine administration. 13C-Aminopyrine breath test results were expressed as a percentage of the administered dose of 13C recovered per hour (% dose/h) and the cumulative percentage of administered dose of 13C recovered over time (% dose cum). Nineteen healthy subjects served as controls. Patients with hepatitis C virus-related chronic hepatitis were divided into subgroups on the basis of histological staging and grading. Results: The 13C-aminopyrine breath test result (% dose/h) at 30 min was significantly different among the three subgroups of subjects (normal subjects, 11.5 ± 3.5; chronic hepatitis patients, 8.1 ± 4.1; cirrhosis patients, 5.0 ± 3.1; P 2) fibrosis scores to be distinguished. The 13C-aminopyrine breath test results (% dose cum) at 30, 60 and 90 min allowed discrimination between normal subjects and chronic hepatitis and cirrhosis patients. The 13C-aminopyrine breath test result (% dose cum) was also able to distinguish between normal subjects and chronic hepatitis patients with high but not low fibrosis scores. Both 13C-aminopyrine breath test results (% dose/h and % dose cum) at 120 min allowed the differentiation between normal subjects and chronic hepatitis patients with high (≥ 6) necro-inflammatory activity. Conclusions: In patients with hepatitis C virus-related chronic liver disease, the 13C-aminopyrine breath test proved to be safe and easy to perform, and was able to evaluate different degrees of liver function impairment which were partly correlated to clinical and histological evaluation. In future studies, 13C-aminopyrine breath test results should be expressed in a standardized fashion to permit comparison.
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- 2002
46. Helicobacter pylorimasks differences in homocysteine plasma levels between controls and type 2 diabetic patients
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S. Giunta, L. Galeazzi, Ivano Testa, Patrizia Bonazzi, Anna Rita Bonfigli, Roberta Galeazzi, Stefano Cenerelli, Daniele Fumelli, C. Sirolla, and Roberto Testa
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education.field_of_study ,medicine.medical_specialty ,biology ,Homocysteine ,Clinical Biochemistry ,Population ,Type 2 Diabetes Mellitus ,General Medicine ,Type 2 diabetes ,Helicobacter pylori ,biology.organism_classification ,medicine.disease ,Biochemistry ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Methylenetetrahydrofolate reductase ,Diabetes mellitus ,medicine ,biology.protein ,Helicobacter ,education - Abstract
BACKGROUND Data in the literature have not clarified whether type 2 diabetes mellitus affects homocysteine plasma levels. Different variables able to influence homocysteine could be the cause of these controversial findings. An important but neglected confounding factor is Helicobacter pylori, which has been demonstrated to be a cause of elevated levels of homocysteine and which is prevalent in the Caucasian population, ranging from 30 to 40% incidence. Starting from these findings we wanted to verify whether differences in homocysteine levels exist between a type 2 diabetic population and a control group, taking into account the presence/absence of Helicobacter pylori. DESIGN The study was carried out on a group of uncomplicated and normotensive type 2 diabetic patients (n = 30, 55.7 +/- 9.7 years) and on a control group (n = 43, 51.2 +/- 11.3 years). On these subjects we evaluated: main parameters of glyco- and lipo-metabolic balance, presence of Helicobacter pylori by 13C Urea Breath Test, plasma homocysteine, vitamin B12, folate and genetic polymorphism of methylenetetrahydrofolate reductase. RESULTS Evaluating the two groups as a whole, significant differences in homocysteine were found when considering Helicobacter pylori presence/absence (14.0 +/- 6.5 vs. 10.6 +/- 4.7 micromol L-1, respectively, P < 0.01) without differences of vitamins and the genetic polymorphism of methylenetetrahydrofolate reductase. The positive interaction found among Helicobacter pylori, diabetes and homocysteine (P = 0.03) taking into account all the other evaluated confounding factors, demonstrates that a significant difference in homocysteine plasma levels exists between diabetics and controls (Helicobacter pylori-negative: diabetics 12.5 +/- 5.6 micromol L-1, controls 9.4 +/- 3.8 micromol L-1; Helicobacter pylori-positive: diabetics 13.6 +/- 5.8 micromol L-1, controls 14.3 +/- 7.0 micromol L-1). CONCLUSIONS Type 2 diabetes seems to induce per se higher levels of homocysteine, which appears to be one of the factors responsible for the increased risk of vascular damage.
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- 2002
47. Diabetes-related quality of life is enhanced by glycaemic improvement in older people
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Anna Rita Bonfigli, Liana Spazzafumo, R. A. Rabini, Andrea Corsonello, Fabrizia Lattanzio, Angela Marie Abbatecola, Giuseppe Paolisso, Paolo Fabbietti, Roberto Testa, Abbatecola, Am, Spazzafumo, L, Fabbietti, P, Testa, R, Rabini, Ra, Bonfigli, Ar, Corsonello, A, Lattanzio, F, and Paolisso, Giuseppe
- Subjects
Male ,medicine.medical_specialty ,Aging ,Outpatient Clinics, Hospital ,Endocrinology, Diabetes and Metabolism ,Validity ,Audit ,Type 2 diabetes ,Cohort Studies ,Diabetes Complications ,Endocrinology ,Hospitals, Urban ,Quality of life ,Cronbach's alpha ,Cost of Illness ,Bayesian multivariate linear regression ,Surveys and Questionnaires ,Diet, Diabetic ,Internal Medicine ,medicine ,Outpatient clinic ,Humans ,Hypoglycemic Agents ,Insulin ,Aged ,Aged, 80 and over ,business.industry ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Diabetes Mellitus, Type 2 ,Italy ,Hyperglycemia ,Physical therapy ,Quality of Life ,Female ,Health Impact Assessment ,business ,Cohort study ,Follow-Up Studies - Abstract
Aims To investigate the validity and reliability of the Audit of Diabetes-Dependent Quality of Life instrument in older Italians with diabetes and to test the association of diabetes-related quality of life with glycaemic control over time. Methods A total of 558 outpatients with Type 2 diabetes from the Diabetic Unit of the Italian National Research Centre on Aging Hospital in Ancona were enrolled to complete questionnaires (Audit of Diabetes-Dependent Quality of Life-19 and the Short-Form-12), and to undergo clinical and biochemical testing at baseline and at 12 months of follow-up. The overall impact of diabetes using the average weighted impact score from the Audit of Diabetes-Dependent Quality of Life questionnaire was calculated. Participants were categorized according to this score as having either less or more negative diabetes-related quality of life. Results Participants had a mean ± sd age of 67.7 ± 9.2 years and 51.8% were male. Factor analysis and Cronbach's coefficient of internal consistency (Cronbach's α = 0.931) confirmed that the 19 domain-specific Audit of Diabetes-Dependent Quality of Life items could be combined into a single scale in this Italian population. The impact score correlated with the physical (r = 0.275; P
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- 2014
48. Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients
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Stefano Genovese, Fabiola Olivieri, Antonio Ceriello, Paolo Fabietti, Anna Rita Bonfigli, Domenico Lio, Giuseppina Candore, Roberto Testa, Massimo Boemi, Liana Spazzafumo, Carmela Rita Balistreri, Calogero Caruso, Claudio Franceschi, Balistreri, CR, Bonfigli, AR, Boemi, M, Olivieri, F, Ceriello, A, Genovese, S, Franceschi, C, Spazzafumo, L, Fabietti, P, Candore, G, Caruso, C, Lio, D, and Testa, R
- Subjects
Adult ,Male ,medicine.medical_specialty ,Genotype ,Article Subject ,T2DM, TLR4, +896A/G SNP, T2DM complications ,Immunology ,Polymorphism, Single Nucleotide ,Lower limb ,Gene Frequency ,Diabetes mellitus ,Internal medicine ,lcsh:Pathology ,medicine ,Humans ,Settore MED/05 - Patologia Clinica ,Genetic Predisposition to Disease ,Allele frequency ,Aged ,Aged, 80 and over ,Settore MED/04 - Patologia Generale ,business.industry ,Confounding ,TLR4 POLYMORPHISM ,Cell Biology ,Middle Aged ,medicine.disease ,Surgery ,Toll-Like Receptor 4 ,Cumulative risk ,Diabetes Mellitus, Type 2 ,Female ,Complication ,business ,Research Article ,lcsh:RB1-214 - Abstract
T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication’s prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P=0.026), lower limb arteriopathy (P=0.013), and the major cardiovascular pathologies (P=0.017). Their cumulative risk was significant (P=0.01), with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642–8.741). Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients.
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- 2014
49. Therapeutic management of chronic hepatitis B in clinical practice: a region-wide survey
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Edoardo G, Giannini, Simona, Marenco, Silvia, Boni, Andrea, Beltrame, Laura A, Nicolini, Lucia, Taramasso, Marcello, Feasi, Alessandro, Grasso, Pasqualina, De Leo, Gianfranco, Percario, Valentina, Bartolacci, Stefania, Artioli, Claudio, Viscoli, Giovanni, Cassola, Roberto, Testa, Marco, Anselmo, Giovanni, Riccio, Vincenzo, Savarino, Antonino, Picciotto, and Ferdinando, Dodi
- Subjects
Male ,Cirrhosis ,Time Factors ,Hepatocellular carcinoma ,Cross-sectional study ,Practice Patterns ,Antiviral therapy ,medicine.disease_cause ,Gastroenterology ,Tertiary Care Centers ,Liver disease ,Seroepidemiologic Studies ,80 and over ,Hepatitis B e Antigens ,Chronic ,Young adult ,Practice Patterns, Physicians' ,Chronic hepatitis ,Outcome ,Aged, 80 and over ,education.field_of_study ,Nucleotide analogs ,Hepatitis B ,Middle Aged ,Treatment Outcome ,Italy ,Disease Progression ,Interferon ,Female ,Adult ,medicine.medical_specialty ,Hepatitis B virus ,Population ,Antiviral Agents ,Young Adult ,Hepatitis B, Chronic ,Internal medicine ,medicine ,Humans ,education ,Aged ,Biomarkers ,Cross-Sectional Studies ,Health Care Surveys ,Interferons ,Physicians' ,business.industry ,medicine.disease ,business - Abstract
GOALS To characterize the clinical and treatment pattern in a large population of hepatitis B virus (HBV) patients managed at tertiary referral centers in clinical practice. BACKGROUND Successful treatment, either with interferon (IFN) or nucleos(t)ide analogs (NUCs), of chronic HBV infection is associated with improved long-term patient outcome. However, in clinical practice, the actual management of these patients is not well characterized, and data regarding treatment pattern in this setting are lacking. METHODS In this cross-sectional study, we evaluated 505 patients chronically infected with HBV alone and who had at least 1-year follow-up. We assessed indication to, rate of, and type of treatment as well as the characteristics of treated patients. RESULTS Overall prevalence of positivity for HBe antigen was 19.3%, and the majority of patients had chronic hepatitis (47.5%). Non-Italian patients represented approximately one third of the population (27.1%). Among patients with indication to antiviral therapy (n=318), treatment was actually carried out in 264 patients (83.0%), prevalently with NUCs (65.9%). IFN-treated patients were younger (P
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- 2014
50. Myasthenia gravis and heart failure: is ivabradine a useful drug?
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Lucia Magni, Claudio Marabotti, Alberto Pellegrinetti, Roberto Testa, and Elio Venturini
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Drug ,Aged, 80 and over ,Heart Failure ,Male ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Benzazepines ,medicine.disease ,Myasthenia gravis ,Treatment Outcome ,Heart failure ,Internal medicine ,Myasthenia Gravis ,Cardiology ,Medicine ,Humans ,Ivabradine ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,media_common - Published
- 2014
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