35 results on '"Santulli, G."'
Search Results
2. Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications
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Gaetano Santulli, Angela Lombardi, Stanislovas S. Jankauskas, Celestino Sardu, Jessica Gambardella, Jankauskas, S. S., Gambardella, J., Sardu, C, Lombardi, A, Santulli, G, Sardu, C., Lombardi, A., and Santulli, G.
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0301 basic medicine ,Islet ,insulin ,medicine.medical_treatment ,Adipose tissue ,β-cells ,Type 2 diabetes ,Review ,Biology ,QH426-470 ,Bioinformatics ,Diabete ,Biochemistry ,NF-κB ,Nephropathy ,NRF2 ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Micro-RNA ,Diabetes mellitus ,medicine ,Genetics ,Molecular Biology ,islets ,Type 1 diabetes ,diabetes ,epigenetics ,Insulin ,MiR-155 ,PBMC ,Epigenetic ,medicine.disease ,Metabolic syndrome ,MafB ,030104 developmental biology ,inflammation ,030220 oncology & carcinogenesis - Abstract
Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 partakes in the phenotypic switch of cells within the islets of Langerhans under metabolic stress. Moreover, miR-155 was shown to regulate insulin sensitivity in liver, adipose tissue, and skeletal muscle. Dysregulation of miR-155 expression was also shown to predict the development of nephropathy, neuropathy, and retinopathy in DM. Here, we systematically describe the reports investigating the role of miR-155 in DM and its complications. We also discuss the recent results from in vivo and in vitro models of type 1 diabetes (T1D) and T2D, discussing the differences between clinical and preclinical studies and shedding light on the molecular pathways mediated by miR-155 in different tissues affected by DM.
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- 2021
3. Advances in the understanding of excitation-contraction coupling: the pulsing quest for drugs against heart failure and arrhythmias
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Gaetano Santulli, Bruno Trimarco, Stanislovas S. Jankauskas, Fahimeh Varzideh, Jessica Gambardella, Urna Kansakar, Kansakar, U., Varzideh, F., Jankauskas, S. S., Gambardella, J., Trimarco, B., and Santulli, G.
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Heart Failure ,medicine.medical_specialty ,business.industry ,Excitation–contraction coupling ,Arrhythmias, Cardiac ,medicine.disease ,Heart Rate ,Internal medicine ,Heart failure ,Correspondence ,medicine ,Cardiology ,Humans ,Pharmacology (medical) ,Cardiology and Cardiovascular Medicine ,business ,Excitation Contraction Coupling ,Human - Published
- 2021
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4. Metabolic Flexibility of Mitochondria Plays a Key Role in Balancing Glucose and Fatty Acid Metabolism in the Diabetic Heart
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Jessica Gambardella, Gaetano Santulli, Angela Lombardi, Gambardella, J., Lombardi, A., and Santulli, G.
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0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Context (language use) ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Diabetic cardiomyopathy ,Diabetes mellitus ,Diabetes Mellitus ,Internal Medicine ,medicine ,Animals ,Humans ,Flexibility (engineering) ,chemistry.chemical_classification ,Fatty acid metabolism ,Chemistry ,Myocardium ,Fatty Acids ,Fatty acid ,Metabolism ,Lipid Metabolism ,medicine.disease ,Mitochondria ,Cell biology ,Glucose ,030104 developmental biology ,Ketone bodies ,Energy Metabolism - Abstract
In order to meet its energy requirements, the heart has the intrinsic capability to metabolize a wide range of energy substrates. In normal conditions, the heart favors fatty acids as the main energetic substrate, followed by carbohydrates, ketone bodies, and, lastly, amino acids (1,2). Yet, the myocardium is able to dynamically switch its metabolism according to substrate availability, in order to attempt to guarantee an efficient pumping function in virtually any scenario (2,3). Mechanistically, this phenomenon seems to be possible, as the different substrates available in the heart compete as source of energy, making the final choice essentially based on the relative substrate concentrations. In a seminal Nature article published in 1961, Schipp et al. (4) demonstrated for the first time that increasing fatty acid availability resulted in a marked inhibition of glucose oxidation. Overall, the high flexibility in selecting the most suitable fuel is considered a fingerprint of a healthy myocardium (1). Accordingly, an impaired metabolic flexibility is strongly linked to cardiac damage and dysfunction (2). In the presence of diverse pathological conditions, cardiac metabolism might lose the ability to use some substrates. Whether this phenomenon is deleterious or actually denotes an adaptive response of the myocardium to keep its metabolic rate remains controversial. However, clarifying this aspect is of crucial importance, especially in order to design new therapeutic strategies. In this context, diabetic cardiomyopathy is one of the most critical knots to untie. In diabetes, despite the hyperglycemic status, a reduced capability to use glucose by myocardium has been reported (5,6). However, whether such impairment in glucose oxidization is an adaptive or maladaptive response of the diabetic heart remains to be elucidated. The matter is highly debated, despite recent evidence …
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- 2020
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5. Aspirin, NOACs, warfarin: which is the best choice to tackle cognitive decline in elderly patients? Insights from the GIRAF and ASCEND-Dementia trials presented at the AHA 2021
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Gaetano Santulli, Bruno Trimarco, Pasquale Mone, Mone, P., Trimarco, B., and Santulli, G.
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medicine.medical_specialty ,Administration, Oral ,Older Adults ,Dabigatran ,Elderly ,Pharmapulse ,medicine ,Humans ,Dementia ,Cognitive Dysfunction ,Pharmacology (medical) ,NOAC ,Cognitive decline ,Intensive care medicine ,Cognitive impairment ,Aspirin ,Cognitive Impairment ,VKA ,Warfarin ,Aged ,business.industry ,Anticoagulants ,medicine.disease ,Cardiology and Cardiovascular Medicine ,business ,Older Adult ,medicine.drug - Published
- 2022
6. Effects of Sodium-Glucose Transporter 2 Inhibitors (SGLT2-I) in Patients With Ischemic Heart Disease (IHD) Treated by Coronary Artery Bypass Grafting via MiECC: Inflammatory Burden, and Clinical Outcomes at 5 Years of Follow-Up
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Celestino Sardu, Massimo Massetti, Nicola Testa, Luigi Di Martino, Gaetano Castellano, Fabrizio Turriziani, Ferdinando Carlo Sasso, Michele Torella, Marisa De Feo, Gaetano Santulli, Giuseppe Paolisso, Raffaele Marfella, Sardu, C., Massetti, M., Testa, N., Martino, L. D., Castellano, G., Turriziani, F., Sasso, F. C., Torella, M., De Feo, M., Santulli, G., Paolisso, G., and Marfella, R.
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medicine.medical_specialty ,endocrine system diseases ,type 2 diabetes mellitus ,minimally invasive extracorporeal circulation ,multi-vessel coronary stenosi ,coronary artery bypass grafting ,Infarction ,RM1-950 ,sodium-glucose transporter 2 inhibitor ,type 2 diabetes mellitus, coronary heart disease ,Internal medicine ,Clinical endpoint ,sodium-glucose transporter 2 inhibitors ,Medicine ,Pharmacology (medical) ,coronary heart disease ,Settore MED/23 - CHIRURGIA CARDIACA ,Stroke ,Pharmacology ,biology ,business.industry ,Proportional hazards model ,C-reactive protein ,Extracorporeal circulation ,Type 2 Diabetes Mellitus ,nutritional and metabolic diseases ,medicine.disease ,medicine.anatomical_structure ,multi-vessel coronary stenosis ,over-inflammation ,biology.protein ,Therapeutics. Pharmacology ,business ,Artery - Abstract
Introduction: Minimally invasive extracorporeal circulation (MiECC) reduced inflammatory burden, leading to best clinical outcomes in patients treated with coronary artery bypass grafting (CABG). Despite this, the patients with type 2 diabetes mellitus (T2DM) vs those without T2DM (non-T2DM) have a worse prognosis, caused by over-inflammation and modulated by sodium-glucose transporter 2 receptors. However, we evaluated the inflammatory burden and clinical outcomes in non-T2DM vs T2DM patients under sodium-glucose transporter 2 inhibitors (SGLT2-I users) vs non-SGLT2-I users at 5 years of follow-up post-CABG via MiECC.Materials and methods: In a multicenter study, we screened consecutive patients with indications to receive CABG. The study endpoints were the inflammatory burden (circulating serum levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 and 6 (IL-1 and IL-6), C-reactive protein (CRP), and leucocytes count) and the clinical outcomes at follow-up of 5 years in non-T2DM vs SGLT2-I users, in non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users.Results: At baseline, and at one year and 5 years of follow-up, the non-T2DM vs SGLT2-I users, non-T2DM vs non-SGLT2-I users, and SGLT2-I users vs non-SGLT2-I users had the lowest values of IL-1, IL-6, and TNF-α (p < 0.05). At one year of follow-up, SGLT2-I users vs non-T2DM and non-SGLT2-I users vs non-T2DM users had a higher rate of all deaths, cardiac deaths, re-myocardial infarction, repeat revascularization, and stroke, and of the composite endpoint (p < 0.05). In a multivariate Cox regression analysis, the composite endpoint was predicted by IL-1 [2.068 (1.367–3.129)], TNF-α [1.989 (1.081–2.998)], and SGLT2-I [0.504 (0.078–0.861)].Conclusion: In T2DM patients, the SGLT2-I significantly reduced the inflammatory burden and ameliorated clinical outcomes at 5 years of follow-up post-CABG via MiECC.
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- 2021
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7. Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia
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Pasquale Mone, Salvatore Frullone, Jessica Gambardella, Eugenio Boccalone, Alessandro Matarese, Gaetano Santulli, Antonella Pansini, Antonio de Donato, Giuseppe Martinelli, Mone, P., Gambardella, J., Pansini, A., de Donato, A., Martinelli, G., Boccalone, E., Matarese, A., Frullone, S., and Santulli, G.
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medicine.medical_specialty ,hypertension ,endocrine system diseases ,QH301-705.5 ,medicine.medical_treatment ,Frail Elderly ,antidiabetic drugs ,frailty ,Antidiabetic drug ,Article ,Anti‐aging research ,age-related disease ,aging ,anti-aging research ,cognitive impairment ,endothelial cells ,hyperglycemia ,metabolism ,metformin ,therapeutic strategies ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Cognitive Dysfunction ,Biology (General) ,Endothelial dysfunction ,Risk factor ,Cognitive decline ,Glycemic ,Aged ,Endothelial Cell ,business.industry ,Insulin ,Therapeutic strategie ,Montreal Cognitive Assessment ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Metformin ,Age‐related disease ,business ,Human ,medicine.drug - Abstract
Endothelial dysfunction is a key hallmark of hypertension, which is a leading risk factor for cognitive decline in older adults with or without frailty. Similarly, hyperglycemia is known to impair endothelial function and is a predictor of severe cardiovascular outcomes, independent of the presence of diabetes. On these grounds, we designed a study to assess the effects of high-glucose and metformin on brain microvascular endothelial cells (ECs) and on cognitive impairment in frail hypertensive patients. We tested the effects of metformin on high-glucose-induced cell death, cell permeability, and generation of reactive oxygen species in vitro, in human brain microvascular ECs. To investigate the consequences of hyperglycemia and metformin in the clinical scenario, we recruited frail hypertensive patients and we evaluated their Montreal Cognitive Assessment (MoCA) scores, comparing them according to the glycemic status (normoglycemic vs. hyperglycemic) and the use of metformin. We enrolled 376 patients, of which 209 successfully completed the study. We observed a significant correlation between MoCA score and glycemia. We found that hyperglycemic patients treated with metformin had a significantly better MoCA score than hyperglycemic patients treated with insulin (18.32 ± 3.9 vs. 14.94 ± 3.8, p <, 0.001). Our in vitro assays confirmed the beneficial effects of metformin on human brain microvascular ECs. To our knowledge, this is the first study correlating MoCA score and glycemia in frail and hypertensive older adults, showing that hyperglycemia aggravates cognitive impairment.
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- 2021
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8. Genetics of adrenergic signaling drives coronary artery calcification
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Gaetano Santulli, Xujun Wang, Pasquale Mone, Jessica Gambardella, Wafiq Khondkar, Gambardella, J., Wang, X., Mone, P., Khondkar, W., and Santulli, G.
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β2-adrenergic receptor ,medicine.medical_specialty ,Vessel ,Coronary Artery Disease ,Coronary artery calcification ,β2 adrenergic receptor ,Adrenergic Agent ,Coronary artery disease ,Adrenergic Agents ,Internal medicine ,Adrenergic signaling ,medicine ,Humans ,business.industry ,Genetic Variation ,Atherosclerosis ,medicine.disease ,Coronary Vessels ,Atherosclerosi ,Cardiology ,Signal transduction ,Cardiology and Cardiovascular Medicine ,business ,Human ,Signal Transduction - Published
- 2020
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9. Cardiac BIN1 Replacement Therapy Ameliorates Inotropy and Lusitropy in Heart Failure by Regulating Calcium Handling∗
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Gaetano Santulli, Jessica Gambardella, John Ferrara, Marco Bruno Morelli, Xu Jun Wang, Gambardella, J., Wang, X. J., Ferrara, J., Morelli, M. B., and Santulli, G.
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dyad ,Inotrope ,medicine.medical_specialty ,Lusitropy ,Calcium handling ,RyR ,heart failure ,arrhythmia ,t-tubule ,T-tubule ,Internal medicine ,medicine ,sympathetic overdrive ,Pressure overload ,Ryanodine receptor ,business.industry ,cBIN1 ,pressure overload ,medicine.disease ,HFpEF ,medicine.anatomical_structure ,Heart failure ,dyads ,calcium handling ,Cardiology ,diastolic dysfunction ,Cardiology and Cardiovascular Medicine ,business ,Editorial Comment ,arrhythmias - Abstract
Heart failure is an important, and growing, cause of morbidity and mortality. Half of patients with heart failure have preserved ejection fraction, for whom therapeutic options are limited. Here we report that cardiac bridging integrator 1 gene therapy to maintain subcellular membrane compartments within cardiomyocytes can stabilize intracellular distribution of calcium-handling machinery, preserving diastolic function in hearts stressed by chronic beta agonist stimulation and pressure overload. This study identifies that maintenance of intracellular architecture and, in particular, membrane microdomains at t-tubules, is important in the setting of sympathetic stress. Stabilization of membrane microdomains may be a pathway for future therapeutic development.
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- 2020
10. Impact of thrombus aspiration in frail STEMI patients
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Antonella Pansini, Fabio Minicucci, Ciro Mauro, Gaetano Santulli, Jessica Gambardella, Pasquale Mone, Mario Rizzo, Mone, P., Gambardella, J., Pansini, A., Rizzo, M., Mauro, C., Minicucci, F., and Santulli, G.
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Aging ,Acute coronary syndrome ,medicine.medical_specialty ,Thrombus aspiration ,Frail Elderly ,medicine.medical_treatment ,Frailty ,STEMI ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Percutaneous Coronary Intervention ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Myocardial infarction ,Aged ,Retrospective Studies ,Thrombectomy ,business.industry ,Coronary Thrombosis ,Incidence (epidemiology) ,Percutaneous coronary intervention ,medicine.disease ,Treatment Outcome ,Heart failure ,Cohort ,Cardiology ,ST Elevation Myocardial Infarction ,Original Article ,Geriatrics and Gerontology ,business - Abstract
Background Despite primary percutaneous coronary intervention (PPCI) is generally considered the best therapy in older frail adults with ST-segment elevation myocardial infarction (STEMI), the incidence of re-hospitalization for cardiovascular diseases remains significant in these patients. Aims We hypothesized that thrombus aspiration (TA) before PPCI could be a useful treatment for reducing mortality and rehospitalizations in frail patients undergoing PPCI for STEMI. Methods We conducted a study comparing PPCI alone vs TA + PPCI in frail STEMI patients. We examined a cohort of consecutive frail patients aged ≥ 65 years with first STEMI treated with PPCI between February 2008 and July 2015 at the Department of Cardiology of the “Cardarelli” Hospital in Naples, Italy. Results The study was completed by 389 patients (PPCI: 195, TA + PPCI: 194). At 1-month follow-up, the rate of death from any cause was 7.0% in patients treated with PPCI alone vs 3.0% in patients treated with TA + PPCI (p 0.036), whereas death from cardiovascular causes was 6.0% in the PPCI group vs 3.0% in the TA + PPCI group (p 0.028). Equally important, the rate of re-hospitalization due to heart failure was 7.5% in the PPCI group vs 4.0% in TA + PPCI group (p 0.025) and the rate of re-hospitalization due to acute coronary syndrome was 10.0% in the PPCI group vs 4.5% in the TA + PPCI group (p 0.016). Conclusion These results indicate the importance of TA in the treatment of STEMI in a group of high-risk patients such as elderly with frailty.
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- 2021
11. Heart failure in diabetes
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Gaetano Santulli, Urna Kansakar, Jessica Gambardella, Fahimeh Varzideh, Angela Lombardi, Scott Wilson, Pasquale Mone, Stanislovas S. Jankauskas, Jankauskas, S. S., Kansakar, U., Varzideh, F., Wilson, S., Mone, P., Lombardi, A., Gambardella, J., and Santulli, G.
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Aging ,Diabetic Cardiomyopathies ,Fibrosi ,Endocrinology, Diabetes and Metabolism ,Diabetic cardiomyopathy ,Bioinformatics ,Endocrinology ,Diabetes mellitus ,Fibrosis ,T1DM ,Adrenergic receptors ,Cardiovascular endocrinology ,Diabetic Cardiomyopathie ,Cause of death ,Cardiomyocytes ,FOXO1 ,ROS ,Phospholamban ,Mitochondria ,medicine.anatomical_structure ,BHB ,Diastolic dysfunction ,Fibroblast ,Senescence ,medicine.medical_specialty ,Diabetes mellitu ,Endothelium ,Bioenergetics ,Fibroblasts ,HFpEF ,Heart failure ,NADH ,Oxidative stress ,T2DM ,VSMC ,Bioenergetic ,Cardiomyocyte ,Adrenergic receptor ,Article ,Internal medicine ,medicine ,Humans ,business.industry ,medicine.disease ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Oxidative stre ,business - Abstract
Heart failure and cardiovascular disorders represent the leading cause of death in diabetic patients. Here we present a systematic review of the main mechanisms underlying the development of diabetic cardiomyopathy. We also provide an excursus on the relative contribution of cardiomyocytes, fibroblasts, endothelial and smooth muscle cells to the pathophysiology of heart failure in diabetes. After having described the preclinical tools currently available to dissect the mechanisms of this complex disease, we conclude with a section on the most recent updates of the literature on clinical management.
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- 2021
12. Cardiovascular Endocrinology: Evolving Concepts and Updated Epidemiology of Relevant Diseases
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Fahimeh Varzideh, Urna Kansakar, Stanislovas S. Jankauskas, Jessica Gambardella, Gaetano Santulli, Varzideh, F., Kansakar, U., Jankauskas, S. S., Gambardella, J., and Santulli, G.
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medicine.medical_specialty ,endocrine hypertension ,Endocrinology, Diabetes and Metabolism ,cardiometabolism ,Endocrine System ,Bioinformatics ,Cardiovascular System ,Diseases of the endocrine glands. Clinical endocrinology ,metabolic syndrome ,Cardiovascular Physiological Phenomena ,Insulin resistance ,Endocrinology ,Diabetes mellitus ,insulin resistance ,NAFLD ,Epidemiology ,medicine ,Humans ,business.industry ,diabetes mellitu ,RC648-665 ,medicine.disease ,HFpEF ,uremic cardiomyopathy ,Endocrine hypertension ,diabetes mellitus ,Metabolic syndrome ,business ,Specialty Grand Challenge ,Human - Published
- 2021
13. L-arginine and covid-19: An update
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Gaetano Santulli, Pasquale Mone, Stanislovas S. Jankauskas, Michael Eacobacci, Scott Wilson, Kwame Donkor, Jessica Gambardella, Ayobami Adebayo, Angela Lombardi, Valentina Trimarco, Urna Kansakar, Fahimeh Varzideh, Adebayo, A., Varzideh, F., Wilson, S., Gambardella, J., Eacobacci, M., Jankauskas, S. S., Donkor, K., Kansakar, U., Trimarco, V., Mone, P., Lombardi, A., and Santulli, G.
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Arginine ,coronavirus ,Review ,Bioinformatics ,medicine.disease_cause ,Cytokine storm ,oxidative stress ,TX341-641 ,Coronavirus ,Endothelial Cell ,Nutrition and Dietetics ,ROS ,Antiviral therapie ,Host-Pathogen Interaction ,Host-Pathogen Interactions ,medicine.symptom ,Human ,Coronavirus disease 2019 (COVID-19) ,viral infections ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Coronaviru ,T cells ,Inflammation ,Immune system ,Immunity ,medicine ,Animals ,Humans ,Endothelium ,antiviral therapies ,Immune response ,COVID-19 ,SARS-CoV-2 ,arginine ,cytokine storm ,endothelium ,immune response ,immunity ,inflammation ,nitric oxide ,nitrosylation ,Nutrition. Foods and food supply ,business.industry ,Animal ,Nitrosylation ,Endothelial Cells ,T cell ,Nitric oxide ,medicine.disease ,COVID-19 Drug Treatment ,Viral infection ,Immune System ,Oxidative stre ,business ,Food Science - Abstract
l-Arginine is involved in many different biological processes and recent reports indicate that it could also play a crucial role in the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present an updated systematic overview of the current evidence on the functional contribution of L-Arginine in COVID-19, describing its actions on endothelial cells and the immune system and discussing its potential as a therapeutic tool, emerged from recent clinical experimentations.
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- 2021
14. A Retinoic Acid Receptor β2 Agonist Improves Cardiac Function in a Heart Failure Model
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Xujun Wang, Roberto Levi, Lorraine J. Gudas, Xiao-Han Tang, Stanislovas S. Jankauskas, Gaetano Santulli, Jessica Gambardella, Tang, X. -H., Gambardella, J., Jankauskas, S., Wang, X., Santulli, G., Gudas, L. J., and Levi, R.
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Cardiac function curve ,Male ,Receptors, Retinoic Acid ,Ischemia ,Pharmacology ,medicine.disease_cause ,Benzoate ,Mice ,medicine ,Myocardial infarction ,Heart Failure ,NADPH oxidase ,biology ,business.industry ,Animal ,Oxidative Stre ,medicine.disease ,Mice, Inbred C57BL ,Retinoic acid receptor ,Disease Models, Animal ,Heart failure ,biology.protein ,Molecular Medicine ,Thiazole ,business ,Oxidative stress ,Ex vivo - Abstract
We previously demonstrated that the selective retinoic acid receptor (RAR) β2 agonist AC261066 reduces oxidative stress in an ex vivo murine model of ischemia/reperfusion. We hypothesized that by decreasing oxidative stress and consequent fibrogenesis, AC261066 could attenuate the development of contractile dysfunction in post-ischemic heart failure (HF). We tested this hypothesis in vivo using an established murine model of myocardial infarction (MI), obtained by permanent occlusion of the left anterior descending coronary artery. Treating mice with AC261066 in drinking water significantly attenuated the post-MI deterioration of echocardiographic indices of cardiac function, diminished remodeling, and reduced oxidative stress, as evidenced by a decrease in malondialdehyde level and p38 mitogen-activated protein kinase expression in cardiomyocytes. The effects of AC261066 were also associated with a decrease in interstitial fibrosis, as shown by a marked reduction in collagen deposition and α-smooth muscle actin expression. In cardiac murine fibroblasts subjected to hypoxia, AC261066 reversed hypoxia-induced decreases in superoxide dismutase 2 and angiopoietin-like 4 transcriptional levels as well as the increase in NADPH oxidase 2 mRNA, demonstrating that the post-MI cardioprotective effects of AC261066 are associated with an action at the fibroblast level. Thus, AC261066 alleviates post-MI cardiac dysfunction by modulating a set of genes involved in the oxidant/antioxidant balance. These AC261066 responsive genes diminish interstitial fibrogenesis and remodeling. Since MI is a recognized major cause of HF, our data identify RARβ2 as a potential pharmacological target in the treatment of HF. SIGNIFICANCE STATEMENT A previous report showed that the selective retinoic acid receptor (RAR) β2 agonist AC261066 reduces oxidative stress in an ex vivo murine model of ischemia/reperfusion. This study shows that AC261066 attenuates the development of contractile dysfunction and maladaptive remodeling in post-ischemic heart failure (HF) by modulating a set of genes involved in oxidant/antioxidant balance. Since myocardial infarction is a recognized major cause of HF, these data identify RARβ2 as a potential pharmacological target in the treatment of HF.
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- 2021
15. miR-7 Regulates GLP-1-Mediated Insulin Release by Targeting β-Arrestin 1
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Gaetano Santulli, Jessica Gambardella, Xujun Wang, Angela Lombardi, Alessandro Matarese, Matarese, A., Gambardella, J., Lombardi, A., Wang, X., and Santulli, G.
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endocrine system ,glucose-stimulated insulin secretion (GSIS) ,miRNA-7 ,medicine.medical_treatment ,Immunoblotting ,β-arrestin 1 ,Article ,Cell Line ,Transcription (biology) ,Glucagon-Like Peptide 1 ,Diabetes mellitus ,Insulin-Secreting Cells ,cAMP ,microRNA ,medicine ,Cyclic AMP ,Humans ,Insulin ,Epigenetics ,Receptor ,Cyclic AMP Response Element-Binding Protein ,lcsh:QH301-705.5 ,Desensitization (medicine) ,diabetes ,epigenetics ,Chemistry ,digestive, oral, and skin physiology ,Type 2 Diabetes Mellitus ,General Medicine ,medicine.disease ,Cell biology ,MicroRNAs ,beta-Arrestin 1 ,lcsh:Biology (General) ,diabete ,epigenetic ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction - Abstract
Glucagon-like peptide-1 (GLP-1) has been shown to potentiate glucose-stimulated insulin secretion binding GLP-1 receptor on pancreatic &beta, cells. &beta, arrestin 1 (&beta, ARR1) is known to regulate the desensitization of GLP-1 receptor. Mounting evidence indicates that microRNAs (miRNAs, miRs) are fundamental in the regulation of &beta, cell function and insulin release. However, the regulation of GLP-1/&beta, ARR1 pathways by miRs has never been explored. Our hypothesis is that specific miRs can modulate the GLP-1/&beta, ARR1 axis in &beta, cells. To test this hypothesis, we applied a bioinformatic approach to detect miRs that could target &beta, ARR1, we identified hsa-miR-7-5p (miR-7) and we validated the specific interaction of this miR with &beta, ARR1. Then, we verified that GLP-1 was indeed able to regulate the transcription of miR-7 and &beta, ARR1, and that miR-7 significantly regulated GLP-1-induced insulin release and cyclic AMP (cAMP) production in &beta, cells. Taken together, our findings indicate, for the first time, that miR-7 plays a functional role in the regulation of GLP-1-mediated insulin release by targeting &beta, ARR1. These results have a decisive clinical impact given the importance of drugs modulating GLP-1 signaling in the treatment of patients with type 2 diabetes mellitus.
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- 2020
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16. No pleotropic effects of linagliptin on atherosclerotic plaques: Case closed
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Mouaz H. Al-Mallah, Gaetano Santulli, Fabien Hyafil, Al-Mallah, M. H., Hyafil, F., and Santulli, G.
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Inflammation ,medicine.medical_specialty ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Dipeptidyl Peptidase 4 ,Linagliptin ,medicine.disease ,Diabete ,Atherosclerosis ,Plaque, Atherosclerotic ,Mice ,Diabetes Mellitus, Type 2 ,Fluorodeoxyglucose F18 ,Internal medicine ,Diabetes mellitus ,Atherosclerosi ,medicine ,Cardiology ,Animals ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Published
- 2020
17. Opposite effects of β 2 -adrenoceptor gene deletion on insulin signaling in liver and skeletal muscle
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Guido Iaccarino, C. Del Giudice, Ersilia Cipolletta, Gaetano Santulli, B. Trimarco, Cipolletta, E., Del Giudice, C., Santulli, G., Trimarco, B., and Iaccarino, G.
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Blood Glucose ,Male ,0301 basic medicine ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Glucose uptake ,medicine.medical_treatment ,Medicine (miscellaneous) ,030204 cardiovascular system & hematology ,Inbred C57BL ,Gi-Go ,β2adrenoceptors ,Mice ,Endocrinology ,0302 clinical medicine ,Insulin receptor substrate ,Receptors ,Homeostasis ,Insulin ,Glucose homeostasis ,Glucose tolerance test ,Cultured ,Nutrition and Dietetics ,medicine.diagnostic_test ,Skeletal ,GTP-Binding Protein alpha Subunits ,Diabetes and Metabolism ,Phenotype ,src-Family Kinases ,Liver ,Adrenergic ,Muscle ,Cardiology and Cardiovascular Medicine ,aPKCζ ,SRC ,Signal Transduction ,medicine.medical_specialty ,Genotype ,Cells ,Knockout ,beta-2 ,Biology ,Transduction ,03 medical and health sciences ,Insulin resistance ,Genetic ,Internal medicine ,medicine ,Animals ,GRB2 Adaptor Protein ,AKT ,Cells, Cultured ,GTP-Binding Protein alpha Subunits, Gi-Go ,Mice, Inbred C57BL ,Mice, Knockout ,Muscle, Skeletal ,Proto-Oncogene Proteins c-akt ,Receptors, Adrenergic, beta-2 ,Transduction, Genetic ,Insulin Resistance ,Insulin tolerance test ,medicine.disease ,Insulin receptor ,030104 developmental biology ,biology.protein - Abstract
Background and aim β 2 -Adrenoceptors (β 2 -ARs) are G protein-coupled receptors (GPCRs) expressed in the major insulin target tissues. The interplay between β 2 -AR and insulin pathways is involved in the maintenance of glucose homeostasis. The aim of this study was to explore the consequences of β 2 -ARs deletion on insulin sensitivity and insulin signaling cascade in metabolically active tissues. Methods and results We evaluated glucose homeostasis in skeletal muscle and liver of β 2 -AR-null mice (β 2 -AR −/− ) by performing in vivo (glucose tolerance test and insulin tolerance test) and ex vivo (glucose uptake and glycogen determination) experiments. β 2 -AR gene deletion is associated with hepatic insulin resistance and preserved skeletal muscle insulin sensitivity. Importantly, we demonstrate that hepatic β 2 -AR regulates insulin-induced AKT activation via Grb2-mediated SRC recruitment through a G i -independent mechanism. Conclusions β-AR stimulation contributes to the development of early stages of insulin resistance progression in the liver. Our findings indicate that the cross-talk between β 2 -AR and insulin signaling represents a fundamental target towards the development of novel therapeutic approaches to treat type 2 diabetes and metabolic syndrome.
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- 2017
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18. In acute HF, intensive and sustained vasodilation did not reduce a composite of death or HF readmission at 180 days
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Gaetano Santulli and Santulli, G.
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medicine.medical_specialty ,business.industry ,Internal medicine ,Heart failure ,Usual care ,Internal Medicine ,medicine ,Cardiology ,Vasodilation ,General Medicine ,business ,medicine.disease - Abstract
SOURCE CITATION: Kozhuharov N, Goudev A, Flores D, et al. Effect of a strategy of comprehensive vasodilation vs usual care on mortality and heart failure rehospitalization among patients with acute heart failure: the GALACTIC randomized clinical trial. JAMA. 2019;322:2292-302. 31846016.
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- 2020
19. Implications of AB0 blood group in hypertensive patients with covid-19
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Gianluca Gatta, Giuseppe Paolisso, Jessica Gambardella, Vincenzo Messina, Antonio Sardu, Paolo Maggi, Raffaele Marfella, Vinicio Codella, Celestino Sardu, Gaetano Santulli, Paolo Cirillo, Sardu, C., Marfella, R., Maggi, P., Messina, V., Cirillo, P., Codella, V., Gambardella, J., Sardu, A., Gatta, G., Santulli, G., and Paolisso, G.
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Male ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Blood Pressure ,Comorbidity ,030204 cardiovascular system & hematology ,Gastroenterology ,0302 clinical medicine ,Risk Factors ,Coagulopathy ,Medicine ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Inflammation Mediator ,biology ,Middle Aged ,Blood Coagulation Factors ,Host-Pathogen Interaction ,Italy ,Host-Pathogen Interactions ,Hypertension ,Female ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,Coronavirus Infections ,Covid-19 ,Case-Control Studie ,Research Article ,Blood Coagulation Factor ,Human ,Adult ,medicine.medical_specialty ,Pneumonia, Viral ,Article ,ABO Blood-Group System ,03 medical and health sciences ,Betacoronavirus ,Von Willebrand factor ,Internal medicine ,ABO blood group system ,Humans ,Pandemics ,Blood Coagulation ,Angiology ,Aged ,Blood type ,Betacoronaviru ,Pandemic ,business.industry ,SARS-CoV-2 ,Coronavirus Infection ,Risk Factor ,Case-control study ,Biomarker ,medicine.disease ,Prospective Studie ,Blood pressure ,lcsh:RC666-701 ,Case-Control Studies ,biology.protein ,business ,Biomarkers - Abstract
BackgroundHypertension is the most frequent co-morbidity in patients with covid-19 infection, and we might speculate that a specific blood group could play a key role in the clinical outcome of hypertensive patients with covid-19.MethodsIn this prospective study, we compared 0 vs. non-0 blood group in hypertensive patients with covid-19 infection. In these patients, we evaluated inflammatory and thrombotic status, cardiac injury, and death events.ResultsPatients in non-0 (n = 92) vs. 0 blood group (n = 72) had significantly different values of activated pro-thrombin time, D-dimer, and thrombotic indexes as Von Willebrand factor and Factor VIII (p p ConclusionsTaken together, our data indicate that non-0 covid-19 hypertensive patients have significantly higher values of pro-thrombotic indexes, as well as higher rate of cardiac injury and deaths compared to 0 patients. Moreover, AB0 blood type influences worse prognosis in hypertensive patients with covid-19 infection.
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- 2020
20. Exploiting grk2 inhibition as a therapeutic option in experimental cancer treatment: Role of p53-induced mitochondrial apoptosis
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Daniela Sorriento, Pietro Campiglia, Michele Ciccarelli, Marina Sala, Gaetano Santulli, Federica Andrea Cerasuolo, Antonella Fiordelisi, Eduardo Sommella, Guido Iaccarino, Maddalena Illario, Jessica Gambardella, Gambardella, J., Fiordelisi, A., Santulli, G., Ciccarelli, M., Cerasuolo, F. A., Sala, M., Sommella, E., Campiglia, P., Illario, M., Iaccarino, G., and Sorriento, D.
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0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,GRK2 ,mitochondrial apoptosis ,lcsh:RC254-282 ,Article ,Thyroid cancer ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,In vivo ,medicine ,Experimental cancer treatment ,P53 ,biology ,Chemistry ,Beta adrenergic receptor kinase ,Mitochondrial apoptosi ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,In vitro ,GRK2 inhibition ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Mitochondrial apoptosis ,Cancer cell ,Cancer research ,biology.protein - Abstract
Simple Summary The involvement of GRK2 in cancer growth and an inverse correlation with p53 levels were suggested in breast cancer. Furthermore, increased GRK2 expression and activity were detected in thyroid cancer, but its effects and mechanisms of action were not investigated yet. This study aimed to explore the role of GRK2 in thyroid cancer both in vitro and in vivo and its crosstalk with p53. We demonstrated that thyroid cancer cells bearing a mutant form of p53 but not p53 null cells rely on GRK2 as a mechanism of proliferation by regulating p53 levels. Indeed, GRK2 indirectly induces p53 degradation through means of its catalytic activity. The pharmacological inhibition of the kinase effectively inhibits cancer growth by inducing p53-dependent mitochondrial pathways of apoptosis. Our results demonstrate a p53-dependent effect of GRK2 in cancer and suggest kinase inhibition as a potential therapeutic strategy for thyroid cancer. Abstract The involvement of GRK2 in cancer cell proliferation and its counter-regulation of p53 have been suggested in breast cancer even if the underlying mechanism has not yet been elucidated. Furthermore, the possibility to pharmacologically inhibit GRK2 to delay cancer cell proliferation has never been explored. We investigated this possibility by setting up a study that combined in vitro and in vivo models to underpin the crosstalk between GRK2 and p53. To reach this aim, we took advantage of the different expression of p53 in cell lines of thyroid cancer (BHT 101 expressing p53 and FRO cells, which are p53-null) in which we overexpressed or silenced GRK2. The pharmacological inhibition of GRK2 was achieved using the specific inhibitor KRX-C7. The in vivo study was performed in Balb/c nude mice, where we treated BHT-101 or FRO-derived tumors with KRX-C7. In our in vitro model, FRO cells were unaffected by GRK2 expression levels, whereas BHT-101 cells were sensitive, thus suggesting a role for p53. The regulation of p53 by GRK2 is due to phosphorylative events in Thr-55, which induce the degradation of p53. In BHT-101 cells, the pharmacologic inhibition of GRK2 by KRX-C7 increased p53 levels and activated apoptosis through the mitochondrial release of cytochrome c. These KRX-C7-mediated events were also confirmed in cancer allograft models in nude mice. In conclusion, our data showed that GRK2 counter-regulates p53 expression in cancer cells through a kinase-dependent activity. Our results further corroborate the anti-proliferative role of GRK2 inhibitors in p53-sensitive tumors and propose GRK2 as a therapeutic target in selected cancers.
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- 2020
21. Functional role of gut microbiota and PCSK9 in the pathogenesis of diabetes mellitus and cardiovascular disease
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Marco Bruno Morelli, Gaetano Santulli, Xujun Wang, Morelli, M. B., Wang, X., and Santulli, G.
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Lipopolysaccharides ,Male ,Diabetes mellitu ,Inflammation ,Wine ,Disease ,Gut flora ,Diet, Mediterranean ,Article ,PCSK9 ,Pathogenesis ,Risk Factors ,Diabetes mellitus ,Atrial Fibrillation ,Medicine ,Humans ,Subtilisins ,Prospective Studies ,Olive Oil ,Aged ,Proportional Hazards Models ,Gastrointestinal tract ,biology ,business.industry ,Microbiota ,Incidence ,Gastrointestinal Microbiome ,NADPH Oxidases ,Middle Aged ,Cardiovascular disease ,medicine.disease ,biology.organism_classification ,Endotoxemia ,Gastrointestinal Tract ,Oxidative Stress ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Immunology ,Multivariate Analysis ,NADPH Oxidase 2 ,Female ,medicine.symptom ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Lipopolysaccharides (LPS) is emerging as a novel risk factor for cardiovascular events (CVEs). Furthermore, in vitro evidence suggested that LPS may elicit proprotein convertase subtilisin/kexin 9 (PCSK9) expression, but their relationship in vivo has not been investigated.We conducted a post-hoc analysis of a prospective, single centre cohort study of 907 patients with non-valvular atrial fibrillation (AF). At baseline, PCSK9, LPS and NADPH oxidase (sNox2-dp) were measured. PCSK9 and LPS were correlated with the incidence of CVEs.Median PCSK9 and LPS were 1200 [900-1970] and 49.9 [15.0-108.2] pg/ml, respectively. LPS and PCSK9 were significantly correlated (rS 0.378, p 0.001). Logistic regression analysis showed that LPS was associated with PCSK9 above the median (odds ratio [OR] 1.727 95% confidence interval [CI] 1.147-2.600 p = 0.009). Other factors associated with PCSK9 above the median were sNox2-dp (OR 1.759 C.I. 95% 1.167-2.650, p = 0.007), use of antiplatelet drugs (OR 0.437 95%CI 0.219-0.871 p = 0.017) and high adherence to Mediterranean diet (OR 0.737 95%CI 0.643-0.845 p = 0.001). Olive oil (OR 0.376 95%CI 0.185-0.763, p = 0.001) and wine (OR 0.460 95%CI 0.289-0.733 p = 0.007) were negatively associated with PCSK9. Patients with concomitant high PCSK9 and LPS (LPS ≥88 pg/ml and PCSK9 ≥1570 pg/ml) had an increased risk of CVEs compared to those with low levels (LPS24.3 pg/ml and PCSK91000 pg/ml, Log-Rank test, p = 0.022).This study demonstrated, for the first time in vivo, that circulating levels of PCSK9 and LPS are associated with a mechanism possibly involving NADPH oxidase activation. Patients with concomitant increase of PCSK9 and LPS showed a higher risk of CVEs.
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- 2019
22. Vitamin C and Cardiovascular Disease: An Update
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Valentina Trimarco, Vanessa Castellanos, Jessica Gambardella, Marco Bruno Morelli, Gaetano Santulli, Morelli, M. B., Gambardella, J., Castellanos, V., Trimarco, V., and Santulli, G.
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0301 basic medicine ,Antioxidant ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,coronavirus ,Review ,Disease ,030204 cardiovascular system & hematology ,Bioinformatics ,Biochemistry ,Dietary supplement ,0302 clinical medicine ,COVID–19 ,oxidative stress ,infections ,Endothelial dysfunction ,Vitamin C ,Stroke ,Liposome ,Hypertension ,Blood pressure ,Ascorbic acid ,Infection ,liposomes ,drug formulations ,Coronaviru ,GULO ,Heart failure ,dietary supplements ,03 medical and health sciences ,Drug formulation ,medicine ,Vascular permeability ,Molecular Biology ,SVCT ,business.industry ,lcsh:RM1-950 ,Cell Biology ,medicine.disease ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Oxidative stre ,business - Abstract
The potential beneficial effects of the antioxidant properties of vitamin C have been investigated in a number of pathological conditions. In this review, we assess both clinical and preclinical studies evaluating the role of vitamin C in cardiac and vascular disorders, including coronary heart disease, heart failure, hypertension, and cerebrovascular diseases. Pitfalls and controversies in investigations on vitamin C and cardiovascular disorders are also discussed.
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- 2020
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23. Diabetes Mellitus and Its Cardiovascular Complications: New Insights into an Old Disease
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Gaetano Santulli, Markus Wallner, Celestino Sardu, Claudio de Lucia, Sardu, Celestino, De Lucia, Claudio, Wallner, Marku, Santulli, Gaetano, Sardu, C., De Lucia, C., Wallner, M., and Santulli, G.
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Blood Glucose ,medicine.medical_specialty ,Article Subject ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Disease ,Risk Assessment ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Endocrinology ,Insulin resistance ,Risk Factors ,Diabetes mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Intensive care medicine ,lcsh:RC648-665 ,Insulin blood ,Extramural ,business.industry ,medicine.disease ,Prognosis ,Editorial ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Insulin Resistance ,Risk assessment ,business ,Introductory Journal Article - Published
- 2019
24. Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update
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Angela Lombardi, John Ferrara, Marco Bruno Morelli, Jessica Gambardella, Gaetano Santulli, Gambardella, J., Lombardi, A., Morelli, M. B., Ferrara, J., and Santulli, G.
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0301 basic medicine ,ITPR ,Cell ,lcsh:Medicine ,autoimmune disease ,Genome-wide association study ,Review ,Diabete ,Calcium in biology ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,IP3 Receptor ,0302 clinical medicine ,cardiovascular disease ,medicine ,cancer ,GWAS ,IP3 Receptors ,Inositol ,Receptor ,Autoimmune disease ,diabetes ,business.industry ,Endoplasmic reticulum ,lcsh:R ,ataxia ,ITPRs ,General Medicine ,mutations ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Alzheimer ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.
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- 2020
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25. Pre-eclampsia and future cardiovascular diseases: How to assess the risk?
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Gaetano Santulli, Mouaz H. Al-Mallah, Santulli, G., and Al-Mallah, M. H.
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Risk ,medicine.medical_specialty ,Eclampsia ,Carotid Artery, Common ,business.industry ,Obstetrics ,Cardiovascular disease ,Atherosclerosis ,medicine.disease ,Pre-Eclampsia ,Cardiovascular Diseases ,Pregnancy ,Risk Factors ,Humans ,Medicine ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Published
- 2019
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26. Stroke prevention: Learning from the master (and COMMANDER)
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Gaetano Santulli and Santulli, G.
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medicine.medical_specialty ,Rivaroxaban ,business.industry ,Death risk ,Atrial fibrillation ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Stroke prevention ,Heart failure ,Internal medicine ,medicine ,Cardiology ,In patient ,030212 general & internal medicine ,business ,Standard therapy ,medicine.drug - Abstract
Adding rivaroxaban to standard therapy in patients with heart failure and no atrial fibrillation did not show any beneficial effect on death risk.
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- 2018
27. Functional role of miRNA in cardiac resynchronization therapy
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Gaetano Santulli, Celestino Sardu, Raffaele Marfella, Giuseppe Paolisso, Sardu, Celestino, Marfella, Raffaele, Santulli, Gaetano, Paolisso, Giuseppe, Sardu, C, and Santulli, G
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medicine.medical_specialty ,HF ,Cardiac fibrosis ,Angiogenesis ,RNA Stability ,medicine.medical_treatment ,Cardiac resynchronization therapy ,Apoptosis ,Biology ,Cardiac Resynchronization Therapy ,Downregulation and upregulation ,Fibrosis ,cardiac fibrosi ,Internal medicine ,microRNA ,Genetics ,medicine ,Humans ,RNA, Messenger ,responder patient ,Heart Failure ,Pharmacology ,Apoptosi ,medicine.disease ,MicroRNAs ,Endocrinology ,Heart failure ,Disease Progression ,Cancer research ,CRT ,Molecular Medicine ,hypertrophy ,Human - Abstract
Heart failure (HF) disease progression is related to numerous adaptive processes including cardiac fibrosis, hypertrophy and apoptosis by activation of the ‘fetal’ gene program and downregulation of mRNA signatures, suggesting the importance of molecular mechanisms that suppress mRNA steady-state levels. miRNAs (miRs) are small, noncoding RNAs that bind mRNAs at their 3′-UTRs, leading to mRNA degradation or inhibition of protein translation. Several miRs are unregulated in response to cellular stress and can modify cellular functions such as proliferation, differentiation and programmed death; these miRs are also regulated in cardiac disease. Cardiac resynchronization therapy improves cardiac performance and myocardial mechanical efficiency. . In this updated critical appraisal we report on the main miRs that play a key role in response to cardiac resynchronization therapy (i.e., responder vs nonresponder HF patients), focusing on the miR-mediated modulation of cardiac angiogenesis, apoptosis, fibrosis and membrane ionic currents.
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- 2014
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28. New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling
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Jessica Gambardella, Guido Iaccarino, Gaetano Santulli, Bruno Trimarco, Gambardella, J., Trimarco, B., Iaccarino, G., and Santulli, G.
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0301 basic medicine ,Electric stimulus ,Contraction (grammar) ,SERCA ,Systole ,Calcium handling ,RyR ,chemistry.chemical_element ,030204 cardiovascular system & hematology ,Calcium ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Excitation Contraction Coupling ,Heart Failure ,Contraction ,Animal ,Mitochondria ,SerCa ,Ryanodine receptor ,Myocardium ,Excitation–contraction coupling ,medicine.disease ,Biomechanical Phenomena ,030104 developmental biology ,chemistry ,Heart failure ,Biophysics ,Human - Abstract
Excitation-contraction (EC) coupling denotes the conversion of electric stimulus in mechanic output in contractile cells. Several studies have demonstrated that calcium (Ca2+) plays a pivotal role in this process. Here we present a comprehensive and updated description of the main systems involved in cardiac Ca2+ handling that ensure a functional EC coupling and their pathological alterations, mainly related to heart failure.
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- 2017
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29. Effects of Alpha Lipoic Acid on Multiple Cytokines and Biomarkers and Recurrence of Atrial Fibrillation Within 1 Year of Catheter Ablation
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Fabio D'Amico, Maria Rosaria Rizzo, Michelangela Barbieri, Igor Caporaso, Raffaele Marfella, Celestino Sardu, Nicola Testa, Giuseppe Paolisso, Gaetano Santulli, Cosimo Sacra, Pasquale Paolisso, Matteo Santamaria, Sardu, Celestino, Santulli, Gaetano, Santamaria, Matteo, Barbieri, Michelangela, Sacra, Cosimo, Paolisso, Pasquale, D'Amico, Fabio, Testa, Nicola, Caporaso, Igor, Paolisso, Giuseppe, Marfella, Raffaele, Rizzo, Maria Rosaria, Sardu, C, Santulli, G, Santamaria, M, Sacra, C, Paolisso, P, D'Amico, F, Testa, N, and Caporaso, I
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Blood Glucose ,Male ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Triglyceride ,Gastroenterology ,Antioxidants ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Peptide Fragment ,Randomized controlled trial ,law ,Recurrence ,Atrial Fibrillation ,Natriuretic Peptide, Brain ,Natriuretic peptide ,Medicine ,Sinus rhythm ,Thioctic Acid ,Atrial fibrillation ,Middle Aged ,Interleukin-10 ,C-Reactive Protein ,Treatment Outcome ,030220 oncology & carcinogenesis ,Anesthesia ,Cardiology ,Catheter Ablation ,Cytokines ,Female ,Antioxidant ,Cardiology and Cardiovascular Medicine ,Human ,medicine.medical_specialty ,medicine.drug_class ,Catheter ablation ,Placebo ,Article ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Peroxynitrous Acid ,Humans ,Risk factor ,Cytokine ,Triglycerides ,Aged ,Postoperative Care ,Cholesterol ,business.industry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Cholesterol, HDL ,Interleukin-8 ,Biomarker ,Cholesterol, LDL ,medicine.disease ,Peptide Fragments ,chemistry ,Tyrosine ,business ,Biomarkers - Abstract
Catheter ablation (CA) is a procedure commonly used to restore sinus rhythm in patients with atrial fibrillation (AF). However, AF recurrence after CA remains a relevant clinical issue. We tested the effects of an oral anti-oxidant treatment (α-lipoic acid, ALA) on AF recurrence post-CA. Patients with paroxysmal AF have been enrolled in a randomized, prospective, double blind, controlled placebo trial. Following CA, patients have been randomly assigned to receive ALA oral supplementation (ALA group) or placebo (control group), and evaluated at baseline and after a 12-month follow-up: 73 patients completed the 12-month follow-up (ALA: 33; control: 40). No significant difference has been detected between the two groups at baseline. Strikingly, one year after CA, ALA therapy significantly reduced serum markers of inflammation. However, there was no significant difference in AF recurrence events at follow-up when comparing ALA to placebo group. Multivariate analysis revealed that the only independent prognostic risk factor for AF recurrence post-CA is age. In conclusion, ALA therapy reduces serum levels of common markers of inflammation in ablated patients. Nevertheless, ALA does not prevent AF recurrence after an ablative treatment.
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- 2016
30. Telemonitoring in heart failure patients treated by cardiac resynchronisation therapy with defibrillator (CRT-D): the TELECART Study
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Giuseppe Paolisso, Matteo Santamaria, Gaetano Santulli, M. di Marino, Maria Rosaria Rizzo, Michelangela Barbieri, Celestino Sardu, Raffaele Marfella, Sardu, C, Santamaria, M, Rizzo, M. R, Barbieri, M, di Marino, M, Paolisso, G, Santulli, Gaetano, Marfella, R., Sardu, C., Santamaria, M., Rizzo, Maria Rosaria, Barbieri, Michelangela, di Marino, M., Paolisso, Giuseppe, Santulli, G, and Marfella, Raffaele
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Cardiac resynchronization therapy ,Monitoring, Ambulatory ,030204 cardiovascular system & hematology ,Medical sciences ,Medical telematics ,Article ,Cardiac Resynchronization Therapy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Medical technology ,Humans ,Telemetry ,030212 general & internal medicine ,cardiovascular diseases ,education ,Implantable cardioverter-defibrillators ,Aged ,Heart Failure ,education.field_of_study ,Ejection fraction ,business.industry ,Left bundle branch block ,Medicine (all) ,Hazard ratio ,Atrial fibrillation ,General Medicine ,medicine.disease ,Defibrillators, Implantable ,Hospitalization ,Heart failure--Patients ,Heart failure ,Ventricular fibrillation ,Cardiology ,cardiovascular system ,Medicine ,Female ,business - Abstract
Aim: Telemonitoring (TM) is a safe and efficient monitoring system for internal cardioverter defibrillator device (ICD) recipients. TM has been used to track info on the clinical status of heart failure patients treated by ICD and/or cardiac resynchronisation therapy defibrillator (CRT-D). The aim of this study was to investigate the impact of TM on clinical outcomes in a population of CRT-D patients with heart failure. Methods: In a multicentre, randomised study, patients with chronic heart failure, New York Heart Association (NYHA) functional class II or III, left bundle branch block, severe left ventricle ejection fraction reduction (LVEF < 35%) have been identified and screened. Results: One hundred and ninety-one patients have been randomised to receive either a CRT-D with TM or a CRT-D with traditional ambulatory monitoring (control group) and completed the 12-month study follow-up. Primary endpoints were all cause death, cardiac death and hospital admission for heart failure. Secondary endpoints were atrial fibrillation, sustained episodes, non-sustained and self terminated ventricular tachyarrhythmia, sustained ventricular tachycardia, and ventricular fibrillation, ICD shocks and percentage of CRT-D responder patients. Univariate analysis identified the following factors predicting hospitalisation: TM, age, chronic kidney disease, hypercholesterolaemia, LVEF and NYHA class. At multivariate analysis, TM was the only factor predicting heart failure hospitalisation (hazard ratio 0.6, 0.42–0.79, 95% CI, p = 0.002), without affecting overall mortality and cardiac deaths events. Conclusions: Taken together, our data indicate the importance of TM in predicting heart failure hospitalisation in patients treated with CRT-D.
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- 2016
31. Metabolic syndrome is associated with a poor outcome in patients affected by outflow tract premature ventricular contractions treated by catheter ablation
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Sardu, Celestino, Carreras, Giovanni, Katsanos, Spyridon, Kamperidis, Vasileios, Pace, Maria Caterina, Passavanti, Maria Beatrice, Fava, Ilaria, Paolisso, Pasquale, Pieretti, Gorizio, Nicoletti, Giovanni Francesco, Paolisso, Giuseppe Marfella, Raffaele, SANTULLI, GAETANO, Sardu, Celestino, Carreras, Giovanni, Katsanos, Spyridon, Kamperidis, Vasileio, Pace, Maria Caterina, Passavanti, Maria Beatrice, Fava, Ilaria, Paolisso, Pasquale, Pieretti, Gorizio, Nicoletti, Giovanni Francesco, Santulli, Gaetano, Paolisso, Giuseppe, Marfella, Raffaele, Sardu, C, Carreras, G, Katsanos, S, Kamperidis, V, Pace, Mc, Passavanti, Mb, Fava, I, Paolisso, P, Pieretti, G, Nicoletti, Gf, Santulli, G, Paolisso, G, and Marfella, R.
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medicine.medical_specialty ,Heart disease ,medicine.medical_treatment ,Biophysics ,Catheter ablation ,Recurrence ,Internal medicine ,medicine ,Humans ,Ventricular outflow tract ,Prospective Studies ,cardiovascular diseases ,Prospective cohort study ,Angiology ,Metabolic Syndrome ,business.industry ,Proportional hazards model ,Metabolic Syndrome X ,medicine.disease ,Ventricular Premature Complexes ,Ventricular Premature Complexe ,Cardiac surgery ,Prospective Studie ,Treatment Outcome ,Catheter Ablation ,cardiovascular system ,Cardiology ,Medicine ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,Research Article ,Human - Abstract
Background The purpose of this study was to investigate the impact of metabolic syndrome (MS) on outcome of catheter ablation (CA) for treatment of frequent premature ventricular contraction beats (PVCs) originating from right ventricular outflow tract (RVOT), left ventricular outflow tract (LVOT) or coronary cusps (CUSPs), in patients with normal ventricular systolic function and absence of cardiac structural disease. Methods In this multicentre prospective study we evaluated 90 patients with frequent PVCs originating from RVOT (n = 68), LVOT (n = 19) or CUSPs (n = 3), treated with CA. According to baseline diagnosis they were divided in patients with MS (n = 24) or without MS (n = 66). The study endpoint was a composite of recurrence of acute or delayed outflow tract ventricular arrhythmia: acute spontaneous or inducible outflow tract ventricular arrhythmia recurrence or recurrence of outflow tract PVCs in holter monitoring at follow up. Results Patients with MS compared to patients without MS showed a higher acute post-procedural recurrence of outflow tract PVCs (n = 8, 66.6%, vs. n = 6, 9.0%, p = 0.005). At a mean follow up of 35 (17-43) months survival free of recurrence of outflow tract PVCs was lower in patients with baseline MS compared to patients without MS diagnosis (log-rank test, p
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- 2014
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32. Impact of diabetes mellitus on the clinical response to cardiac resynchronization therapy in elderly people
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Raffaele Marfella, Celestino Sardu, Gaetano Santulli, Sardu, C, Marfella, Raffaele, Santulli, G., Sardu, Celestino, and Santulli, Gaetano
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Male ,medicine.medical_treatment ,Pharmaceutical Science ,Angiotensin-Converting Enzyme Inhibitors ,Longitudinal Studie ,Diabete ,Cardiac Resynchronization Therapy ,Elderly ,Elderly people ,Age Factor ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Genetics (clinical) ,Aged, 80 and over ,Medicine (all) ,Age Factors ,Treatment Outcome ,Cardiology ,Molecular Medicine ,Female ,Cardiology and Cardiovascular Medicine ,Human ,medicine.medical_specialty ,Cardiotonic Agents ,Adrenergic beta-Antagonists ,Cardiac resynchronization therapy ,Heart failure ,Follow-Up Studie ,Genetic ,Internal medicine ,Diabetes mellitus ,Genetics ,medicine ,Humans ,Cardiotonic Agent ,Aged ,business.industry ,Insulin ,Type 2 Diabetes Mellitus ,Adrenergic beta-Antagonist ,Angiotensin-Converting Enzyme Inhibitor ,medicine.disease ,Prospective Studie ,Diabetes Mellitus, Type 2 ,Implant ,business ,Follow-Up Studies - Abstract
Heart failure (HF) and type 2 diabetes mellitus (T2DM) exhibit a well-established interrelationship and a growing prevalence, in particular in elderly people. Cardiac resynchronization therapy (CRT) has been shown to improve myocardial function in patients with HF and cardiac dyssynchrony. However, reports on CRT in diabetic elderly patients are limited and controversial. Therefore, the aim of the present study was to investigate the functional role of T2DM on the effectiveness of CRT at advanced age. In this single-center prospective study, we enrolled 72 HF patients over 75 years old with and without T2DM who underwent CRT implant. Detailed clinical and instrumental data, including cardiac ultrasound analysis, 6-min walk test, and quality-of-life evaluation, were collected at baseline and at 1-year follow-up. At the time of implantation, 44.4 % of patients had T2DM, of which 62.5 % were well controlled with diet and hypoglycemic drugs and 37.5 % were treated by insulin therapy. After 1 year, CRT improved myocardial ventricular geometry and functional capacity in a comparable proportion of diabetic and non-diabetic patients alongside with a similar amelioration in the functional status. Taken together, our findings demonstrate that diabetic patients >75 years old exhibit a response to CRT that is comparable to non-diabetic subjects.
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- 2014
33. Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus
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N K, Mishra, N, Ahmed, A, Davalos, H K, Iversen, T, Melo, L, Soinne, N, Wahlgren, K R, Lees, A, Alexandrov, and Santulli, G.
- Subjects
Male ,Acute coronary syndrome ,medicine.medical_specialty ,medicine.medical_treatment ,Brain Ischemia ,Diabetes Complications ,Modified Rankin Scale ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Thrombolytic Therapy ,Acute ischemic stroke ,Stroke ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Odds ratio ,Thrombolysis ,medicine.disease ,Confidence interval ,Logistic Models ,Treatment Outcome ,Concomitant ,Tissue Plasminogen Activator ,Physical therapy ,Cardiology ,Female ,Neurology (clinical) ,business ,Follow-Up Studies - Abstract
Patients with concomitant diabetes mellitus (DM) and prior stroke (PS) were excluded from European approval of alteplase in stroke. We examined the influence of DM and PS on the outcomes of patients who received thrombolytic therapy (T; data from Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) compared to nonthrombolyzed controls (C; data from Virtual International Stroke Trials Archive).We selected ischemic stroke patients on whom we held data on age, baseline NIH Stroke Scale score (NIHSS), and 90-day modified Rankin Scale score (mRS). We compared the distribution of mRS between T and C by Cochran-Mantel-Haenszel (CMH) test and proportional odds logistic regression, after adjustment for age and baseline NIHSS, in patients with and without DM, PS, or the combination. We report odds ratios (OR) for improved distribution of mRS with 95% confidence interval (CI) and CMH p value.Data were available for 29,500 patients: 5,411 (18.5%) had DM, 5,019 had PS (17.1%), and 1,141 (5.5%) had both. Adjusted mRS outcomes were better for T vs C among patients with DM (OR 1.45 [1.30-1.62], n = 5,354), PS (OR 1.55 [1.40-1.72], n = 4,986), or concomitant DM and PS (OR 1.23 [0.996-1.52], p = 0.05, n = 1,136), all CMH p0.0001. These are comparable to outcomes between T and C among patients with neither DM nor PS: OR = 1.53 (1.42-1.63), p0.0001, n = 19,339. There was no interaction on outcome between DM and PS with alteplase treatment (tissue plasminogen activator × DM × PS, p = 0.5). Age ≤80 years or80 years did not influence our findings.Outcomes from thrombolysis are better than the controls among patients with DM, PS, or both. We find no statistical justification for the exclusion of these patients from receiving thrombolytic therapy.
- Published
- 2012
34. Atrial function in patients undergoing CRT
- Author
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Gaetano Santulli, Cristofaro D'Ascia, Vittoria Marino, Salvatore D'Ascia, Santulli, G., D'Ascia, S., Marino, V., and D'Ascia, C.
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Cardiac resynchronization therapy ,Ventricular Function, Left ,Cardiac Resynchronization Therapy ,Ventricular Dysfunction, Left ,Heart Conduction System ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Intensive care medicine ,Ventricular remodeling ,Heart Failure ,Lv function ,Ventricular Remodeling ,business.industry ,medicine.disease ,Radiology Nuclear Medicine and imaging ,Heart failure ,cardiovascular system ,Cardiology ,Female ,Hypertrophy, Left Ventricular ,Electrical conduction system of the heart ,Cardiology and Cardiovascular Medicine ,business - Abstract
We read with great interest the paper by Carluccio et al. ([1][1]) regarding the impact of left ventricular (LV) remodeling on the response to cardiac resynchronization therapy (CRT). In this elegant study, the authors performed a comprehensive assessment of LV function, showing that extensive LV
- Published
- 2012
35. Development of atrial fibrillation in recipients of cardiac resynchronization therapy: the role of atrial reverse remodelling
- Author
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Salvatore Luca D'Ascia, Gaetano Santulli, Cristofaro D'Ascia, Santulli, G., D'Ascia, S. L., and D'Ascia, C.
- Subjects
Male ,medicine.medical_specialty ,Ventricular Remodeling ,business.industry ,medicine.medical_treatment ,Cardiac resynchronization therapy ,Atrial fibrillation ,medicine.disease ,Cardiac Resynchronization Therapy ,Text mining ,Heart Rate ,Internal medicine ,Atrial Fibrillation ,medicine ,Cardiology ,Humans ,Female ,Cardiology and Cardiovascular Medicine ,business - Published
- 2011
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