80 results on '"Bucciarelli, L"'
Search Results
52. Bicocca through the eyes of photographer Luca Bigazzi in the film directed by Silvio Soldini
- Author
-
De Nicola, A, Biondillo, G, Bollini, L, Bucciarelli, L, Centovalli, B, Corsini, B, Dell’Agnese, E, De Nicola, A, Lupo, G, Mantegazza, R, Messa, C, Mutti, C, Rimoldi, L, Ruspini, E, Scarazzato, A, Vergani, L, Vismara, N, Zocchi, P, Zuccoli, F, Bigatti, G, and Nuvolati ,G more...
- Subjects
M-PED/03 - DIDATTICA E PEDAGOGIA SPECIALE ,interview, narrative, storytelling, humanities, art, cinema, photography, visual culture, heritage education - Abstract
from an interview with Luca Bigazzi, the photographer, born this text.
- Published
- 2019
53. Ghrelin stimulates adrenocorticotrophic hormone (ACTH) secretion by human ACTH-secreting pituitary adenomas in vitro
- Author
-
Samantha Pesce, Andrea Saccani, Marco Losa, F. Pecori Giraldi, Francesco Cavagnini, L. G. Bucciarelli, Massimo Scacchi, Pecori Giraldi, Francesca, Bucciarelli, L. G., Saccani, A., Scacchi, M., Pesce, S., Losa, M., and Cavagnini, F. more...
- Subjects
Cortisol secretion ,Adenoma ,Adult ,Male ,endocrine system ,medicine.medical_specialty ,Pituitary gland ,Corticotropin-Releasing Hormone ,Endocrinology, Diabetes and Metabolism ,Peptide Hormones ,Adrenocorticotropic hormone ,Biology ,In Vitro Techniques ,Endocrine and Autonomic System ,Cellular and Molecular Neuroscience ,Corticotropin-releasing hormone ,Endocrinology ,Anterior pituitary ,Adrenocorticotropic Hormone ,Pituitary Gland, Anterior ,Internal medicine ,medicine ,Animals ,Humans ,Corticotroph ,Pituitary ACTH Hypersecretion ,Corticotrophs ,Pituitary tumour ,Animal ,In Vitro Technique ,Endocrine and Autonomic Systems ,Pituitary ACTH hypersecretion ,digestive, oral, and skin physiology ,Middle Aged ,medicine.disease ,Ghrelin ,ACTH ,Rats ,medicine.anatomical_structure ,ACTH-Secreting Pituitary Adenoma ,Peptide Hormone ,Rat ,Cushing's disease ,Female ,Corticotropic cell ,hormones, hormone substitutes, and hormone antagonists ,Human - Abstract
Ghrelin is a brain-gut peptide with wide-ranging endocrine, metabolic, cardiovascular and neural effects. Ghrelin, like its synthetic counterparts, the growth hormone (GH) secretagogues, has been shown to markedly stimulate adrenocorticotrophic hormone (ACTH) and cortisol secretion in humans and the ACTH-releasing effect of GH secretagogues is even greater in patients with pituitary ACTH-secreting tumours. Furthermore, these tumours synthesize ghrelin itself, suggesting an intrapituitary ghrelin circuit. The aim of the present study was to evaluate the effect of ghrelin on ACTH secretion by human pituitary corticotroph tumours in vitro to test the functionality of this circuit. Nine ACTH-secreting pituitary tumours (four microadenomas, five macroadenomas) were collected during surgery and incubated with 10-100nM human ghrelin or with 10nM human corticotrophin-releasing hormone (CRH). Control experiments were performed in rat anterior pituitary primary cultures. ACTH secretion was assessed after 4h and 24h incubation by immunometric assay. After 4h of incubation with ghrelin, medium ACTH concentrations were two- to ten-fold higher compared to ACTH concentrations in unstimulated wells. The ACTH-releasing effect of ghrelin was significantly less than the response elicited by 10nM CRH (up to 40-fold) Similar results were obtained after 24h of incubation and a superimposable response pattern was observed in rat anterior pituitary primary cultures. The present study demonstrates that the endogenous GH secretagogue, ghrelin, stimulates ACTH secretion directly from human tumoural corticotrophs, as well as from normal rat pituitary, and indicates that the marked ACTH release elicited by ghrelin in patients with Cushing's disease in vivo is due, at least in part, to its action on the pituitary tumour. However, the reversal of the response pattern reported in vivo, with ghrelin proving a lesser stimulant than CRH in vitro, suggests that additional, suprapituitary mechanisms are involved in the in vivo response. Moreover, these data uphold the concept of a functional intratumoural ghrelin paracrine circuit in human corticotroph adenomas. © 2007 The Authors. Journal Compilation © 2007 Blackwell Publishing Ltd. more...
- Published
- 2007
54. Pharmacological regression of atherosclerotic plaque in patients with type 2 diabetes.
- Author
-
Bucciarelli L, Andreini D, Stefanini G, Fiorina RM, Francone M, Catapano F, Lunati ME, Conte E, Marchetti D, and Fiorina P
- Abstract
Atherosclerosis of the coronary arteries continues to be one of the major global health burdens and acute coronary syndrome is responsible annually for at least 30 % of all deaths globally. Acute coronary syndrome may be the consequence of thrombus formation after erosion or rupture of obstructive or non-obstructive atherosclerotic plaque. The rupture of plaques is mostly caused by mechanical stress usually called cap fatigue. Vulnerable plaques are characterized by a softer atheromatous core and a thinner fibrous cap, with inflammation and hypercholesterolemia playing a crucial role in the atherothrombotic process. Based on animal studies that extend back to the 1920s, regression of atherosclerotic plaques in humans has just started to be considered and pursued. The idea that the human atherosclerotic plaques could regress at all met an important resistance over the decades; indeed, advanced plaques contain components, such as necrosis, calcification and fibrosis, which are hard to be removed. However, new animal models and imaging technics allowed a more complete and accurate quantitative assessment of plaque volume and are shedding new light on atherosclerosis regression. In this review, we are revisiting the existence of atherosclerosis regression in preclinical and clinical studies, with a focus on the latest mechanistic insights and on the newest pharmacological agents, particularly in patients with diabetes. Interestingly, we suggested that based on literature insights and preclinical studies, a combination of drugs to target hyperglycemia, dyslipidemia and inflammation may be desirable for a fast-track Pharmacological regression of atherosclerotic plaque in patients with type 2 diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.) more...
- Published
- 2025
- Full Text
- View/download PDF
55. Reply to the letter comment of Su Boon Yong MD, PhD and colleagues to: Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE- 2 study.
- Author
-
Berra C, Manfrini R, Bifari F, Cipponeri E, Ghelardi R, Centofanti L, Mortola U, Lunati E, Bucciarelli L, Cimino V, and Folli F
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. more...
- Published
- 2025
- Full Text
- View/download PDF
56. Clinical heterogeneity of feeding and eating disorders: using personality psychopathology to differentiate "simplex" and "complex" phenotypes.
- Author
-
Colizzi M, Comacchio C, Garzitto M, Bucciarelli L, Candolo A, Cesco M, Croccia V, Ferreghini A, Martinelli R, Nicotra A, Sebastianutto G, and Balestrieri M
- Subjects
- Humans, Female, Adult, Male, Young Adult, Personality, Personality Disorders diagnosis, Personality Disorders psychology, Personality Disorders epidemiology, Adolescent, Body Mass Index, MMPI, Feeding and Eating Disorders psychology, Feeding and Eating Disorders diagnosis, Phenotype
- Abstract
Background: To investigate Feeding and Eating Disorders (FED) heterogeneity based on the co-occurrence of FED symptoms and personality psychopathology, on the hypothesis that empirical profiles would not confirm current FED categories but identify unique phenotypes carrying different levels of clinical complexity., Methods: Latent Profile Analysis profiled FED patients based on the assessment of both FED symptoms, through the Eating Disorders Inventory, third version (EDI-3), and personality characteristics, through the Minnesota Multiphasic Personality Inventory-2. Then, profiles were compared across socio-demographic and clinical characteristics., Results: Among 109 eligible patients, three FED profiles were identified: (i) FED simplex (low eating symptoms, absence of dysfunctional personality); (ii) FED simplex-severe (high eating symptoms only); and (iii) FED complex-severe (high eating symptoms and dysfunctional personality). Despite an uneven distribution (χ
2 (6) = 15.20, adjusted-p = 0.029), FED profiles did not unequivocally confirm clinical diagnoses (e.g., Anorexia Nervosa). A difference in Body Mass Index (BMI) was observed (K(2) = 15.06, adjusted-p = 0.001), but lower BMI did not identify the most severe group. Profiles differed in EDI-3 overall scores (e.g., Eating Disorder Risk Composite: K(2) = 43.08, adjusted-p < 0.001), Body Uneasiness Test Global Severity Index (GSI: K(2) = 29.33, adjusted-p < 0.001), Binge Eating Scale severity (K(2) = 25.49, adjusted-p < 0.001), number of psychiatric (K(2) = 8.79, adjusted-p = 0.021) and personality diagnoses (K(2) = 11.86, adjusted-p = 0.005), and Symptom Checklist-90-Revised GSI (F(2,103) = 37.68, adjusted-p < 0.001), with FED complex-severe patients being generally the most severely impaired in terms of FED symptoms, body concerns, depersonalization, and psychiatric comorbidities., Conclusions: Findings support the hypothesis of distinguishing FED simplex and complex phenotypes, based on the co-occurrence of dysfunctional personality, with implications for FED severity and clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Department of Medicine (DMED) at the University of Udine (133/2023). Participants provided their written informed consent to participate in this study. Competing interests: Marco Colizzi has been a consultant/advisor to GW Pharma Limited, GW Pharma Italy SRL, and F. Hoffmann-La Roche Limited, outside of this work. The other authors declare no conflict of interest., (© 2024. The Author(s).) more...- Published
- 2024
- Full Text
- View/download PDF
57. Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE-2 study.
- Author
-
Berra C, Manfrini R, Bifari F, Cipponeri E, Ghelardi R, Centofanti L, Mortola U, Lunati E, Bucciarelli L, Cimino V, and Folli F
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Body Weight drug effects, Glycemic Control, Glycated Hemoglobin metabolism, Glycated Hemoglobin analysis, Drug Therapy, Combination, Heart Disease Risk Factors, Treatment Outcome, Immunoglobulin Fc Fragments therapeutic use, Immunoglobulin Fc Fragments adverse effects, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 blood, Recombinant Fusion Proteins therapeutic use, Glucagon-Like Peptides analogs & derivatives, Glucagon-Like Peptides therapeutic use, Glucagon-Like Peptides adverse effects, Obesity drug therapy, Obesity complications, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Sodium-Glucose Transporter 2 Inhibitors adverse effects, Cardiovascular Diseases prevention & control, Cardiovascular Diseases etiology, Blood Glucose drug effects, Hypoglycemic Agents therapeutic use, Hypoglycemic Agents adverse effects
- Abstract
We evaluated the effects on glycemic control and body weight of a GLP1-RA in obese type 2 diabetic patients treated with SGLT2-inhibitors and other hypoglycemic agents and/or insulin, in a real-world setting. A cohort of 583 type 2 diabetic outpatients treated with a SGLT2 inhibitor and/or other anti-diabetic medications were examined. Because patients had suboptimal glycemic control, the GLP1-RA Dulaglutide was added to ongoing medications. At 6 months, 334 patients had a follow-up visit. Patients were classified in terms of cardiovascular risk (CVR) employing the ESC-EASD 2019 criteria, with the AWARE app. The study's primary endpoints were changes in: 1) HbA1c level, 2) BMI, and 3) body weight after six months of treatment. Secondary endpoints were evaluation of Dulaglutide addition in type 2 diabetic patients: 1) with more or less than ten years of T2DM; 2) more or less than 75 years of age and in different subgroups of CVR. In the 334 patients which had a 6 months follow-up visit, age was 65,9+9,8; 33.5 % (112) were females and 66.5 % (222) were males. After six months of Dulaglutide treatment, we found a significant reduction in HbA1c levels (8.0+10.5 mmol/mol; p<0.0001) and in body mass index (1.1+1.1 kg/m
2 ; p<0.0001). Efficacy of Dulaglutide was not affected by different CVD risk categories, age and T2DM duration. This real world study provides evidence for significant reductions in HbA1c level, body mass index and body weight in obese type 2 diabetic patients who received add-on treatment with the weekly GLP-1RA, Dulaglutide., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...- Published
- 2024
- Full Text
- View/download PDF
58. Murphy's Law and Aesthetic Surgery: Are Outcomes Worse in Medical Doctor and Very Important Patients?
- Author
-
Zingaretti N, De Francesco F, Riccio M, Robiony M, Tel A, Sembronio S, Bucciarelli L, and Parodi PC
- Subjects
- Humans, Female, Male, Adult, Middle Aged, Surgery, Plastic legislation & jurisprudence, Surgery, Plastic statistics & numerical data, Physicians statistics & numerical data, Physicians psychology, Plastic Surgery Procedures statistics & numerical data, Plastic Surgery Procedures methods, Retrospective Studies, Postoperative Complications
- Abstract
Background and Objectives : Surgeons have long been aware of Murphy's Law: "If anything can go wrong, it will". When applied to surgery, Murphy's Law suggests that if there is a way that an operation can be set up incorrectly then someday, somewhere, it will be set up incorrectly. This paper focuses on complications in medical doctor (MD) and VIPs during aesthetic surgery. Materials and Methods : We evaluated the clinical results of 368 MDs/VIPs (group 1) and 368 non-MDs/VIPs (group 2) who underwent aesthetic surgery (upper blepharoplasty, facelift, breast augmentation) between January 2010 and September 2021. The minimum follow-up after surgery was 2 years. Results : There was no statistically significant difference in the rate of complications between the two groups. Among the treated patients, the percentage of complications was similar to what has been reported in the literature. Interestingly, the time spent in surgery was longer, and there was an increased number of admissions to outpatient clinics in group 1. Conclusions : We suggest changing the current perception of Murphy's Law regarding complications in MD patients/VIPs undergoing aesthetic surgery. more...
- Published
- 2024
- Full Text
- View/download PDF
59. A new glucose monitoring system for the intermittent monitoring of interstitial glucose values in patients with diabetes mellitus.
- Author
-
Rossi A, Rossi G, Montefusco L, Cimino V, Pastore I, Gandolfi A, Bucciarelli L, Loretelli C, Boci D, D'Addio F, Lunati ME, and Fiorina P
- Abstract
Objectives: Glucose monitoring in diabetes is changing overtime with a constant development of new devices for continuous glucose monitoring (CGM). Aim of this observational, prospective study was to evaluate the clinical performance of a novel intermittently scanned CGM system, the Glunovo Flash in a cohort of patients with type 1 diabetes., Methods: A total of 45 patients with T1D followed at the Endocrinology Unit of the ASST-FBF-Sacco (Milan) were enrolled. All patients were habitual CGM users and were asked to wear simultaneously the Glunovo Flash system and their habitual CGM device for 14 days. A comparison of CGM glucose metrics was performed. Patients' opinions on the new device were also collected., Results: Thirty-five patients completed the study period of two weeks (7 habitual real time CGM users, 28 habitual intermittently scanned CGM users). Mean Time In Range resulted significantly higher with the novel studied sensor respect to intermittently scanned CGM comparator. No differences were found considering other glucose metrics. A positive correlation was found between the Time In Range recorded by Glunovo Flash and intermittently scanned CGM comparators as well as for Time Above Range, Glucose Management Indicator, Time Below Range and Coefficient of Variation. No correlations were found between glucose metrics recorded by Glunovo Flash and real time CGM comparators. Patients reported a positive experience of use with the new sensor but some elements appeared improvable., Conclusions: The CGM device Glunovo Flash for patients with diabetes shows similar performance to other intermittently scanned CGM systems., Competing Interests: Conflict of interestOn behalf of all authors the corresponding author states that they have no other conflict of interest related to the work submitted for publication. No financial interests are directly or indirectly related to the work submitted., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.) more...
- Published
- 2024
- Full Text
- View/download PDF
60. Vaccinome landscape in nearly 620,000 patients with diabetes.
- Author
-
D'Addio F, Lazzaroni E, Lunati ME, Preziosi G, Ercolanoni M, Turola G, Marrocu C, Cicconi G, Sharma S, Scarioni S, Montefusco L, Pastore I, Morpurgo PS, Rossi A, Gandolfi A, Tinari C, Rossi G, Ben Nasr M, Loretelli C, Fiorina RM, Grassa B, Terranova R, Bucciarelli L, Berra C, Cereda D, Zuccotti G, Borriello CR, and Fiorina P more...
- Abstract
Introduction: Type 1 (T1D) and type 2 diabetes (T2D) are associated with an elevated incidence of infectious diseases and a higher risk of infections-related hospitalization and death. In this study, we delineated the "vaccinome" landscape obtained with a large immunization schedule offered by the Regional Government of Lombardy in a cohort of 618,396 patients with diabetes (T1D and T2D)., Methods: Between September 2021 and September 2022, immunization coverage for influenza, meningococcus, pneumococcus, and herpes zoster was obtained from the public computerized registry of the healthcare system of Lombardy Region (Italy) in 618,396 patients with diabetes and in 9,534,087 subjects without diabetes. Type of diabetes, age, mortality, and hospitalizations were retrospectively analyzed in vaccinated and unvaccinated patients., Results: Among patients with diabetes (T1D and T2D), 44.6% received the influenza vaccine, 10.9% the pneumococcal vaccine, 2.5% the anti-meningococcus vaccine and 0.7% the anti-zoster vaccine. Patients with diabetes immunized for influenza, zoster and meningococcus showed a 2-fold overall reduction in mortality risk and a decrease in hospitalizations. A 3-fold lower risk of mortality and a decrease in hospitalizations for both cardiac and pulmonary causes were also observed after influenza, zoster, and meningococcus immunization in older patients with diabetes., Conclusions: Immunization coverage is still far from the recommended targets in patients with diabetes. Despite this, influenza vaccination protected nearly 3,800 per 100,000 patients with diabetes from risk of death. The overall impressive decrease in mortality and hospitalizations observed in vaccinated patients strengthens the need for scaling up the "vaccinome" landscape in patients with diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.) more...
- Published
- 2024
- Full Text
- View/download PDF
61. Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide.
- Author
-
Lunati ME, Cimino V, Bernasconi D, Gandolfi A, Morpurgo PS, Tinari C, Lazzaroni E, Baruffaldi L, Muratori M, Montefusco L, Pastore I, Rossi A, Franzetti IG, Muratori F, Manfrini R, Disoteo OE, Terranova R, Desenzani P, Girelli A, Ghelardi R, D'Addio F, Ben Nasr M, Berra C, Folli F, Bucciarelli L, and Fiorina P more...
- Subjects
- Humans, Benzhydryl Compounds therapeutic use, Blood Glucose, Body Weight, Creatinine, Glucose, Glycated Hemoglobin, Hypoglycemic Agents therapeutic use, Treatment Outcome, Diabetes Mellitus, Type 2 drug therapy, Glucagon-Like Peptides, Glucosides, Sodium-Glucose Transporter 2 Inhibitors therapeutic use
- Abstract
Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.) more...
- Published
- 2024
- Full Text
- View/download PDF
62. Daytime hypoglycemic episodes during the use of an advanced hybrid closed loop system.
- Author
-
Rossi A, Montefusco L, Reseghetti E, Pastore IF, Rossi G, Usuelli V, Loretelli C, Boci D, Ben Nasr M, D'Addio F, Bucciarelli L, Argenti S, Morpurgo P, Lunati ME, and Fiorina P
- Subjects
- Humans, Blood Glucose, Retrospective Studies, Insulin therapeutic use, Insulin Infusion Systems, Hypoglycemic Agents therapeutic use, Glucose therapeutic use, Blood Glucose Self-Monitoring, Hypoglycemia prevention & control, Hypoglycemia chemically induced, Diabetes Mellitus, Type 1 drug therapy
- Abstract
Aims: The use of advanced hybrid closed loop systems is spreading due to the beneficial effects on glycometabolic control obtained in patients with type 1 diabetes. However, hypoglycemic episodes can be sometimes a matter of concern. We aim to compare the hypoglycemic risk of an advanced hybrid closed loop system and a predictive low glucose suspend sensor augmented pump., Methods: In this retrospective three months observational study, we included 30 patients using Medtronic Minimed™ 780G advanced hybrid closed loop system and 30 patients using a Medtronic Minimed™ predictive low glucose suspend sensor augmented pump., Results: The advanced hybrid closed loop system reduced the time spent above 180 mg/dL threshold and increased the time in range as compared to the predictive low glucose suspend. No severe hypoglycemia occurred in both groups and no differences were observed in the percentage of time spent below 70 mg/dl and 54 mg/dl glucose threshold. Nevertheless, more hypoglycemic episodes were recorded during daytime, but not in nighttime, with the use of the advanced hybrid closed loop system., Conclusions: Our results confirmed the general improvement of glycemic outcomes obtained with the advanced hybrid closed loop system; however more hypoglycemic episodes during daytime were evident., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.) more...
- Published
- 2023
- Full Text
- View/download PDF
63. AWARE A novel web application to rapidly assess cardiovascular risk in type 2 diabetes mellitus.
- Author
-
Berra C, Manfrini R, Mirani M, Bucciarelli L, Zakaria AS, Piccini S, Ghelardi R, Lunati ME, Rodovalho S, Bifari F, Fiorina P, and Folli F
- Subjects
- Humans, Middle Aged, Aged, Hypoglycemic Agents therapeutic use, Retrospective Studies, Risk Factors, Heart Disease Risk Factors, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 chemically induced, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology
- Abstract
Aim: To describe the development of the AWARE App, a novel web application for the rapid assessment of cardiovascular risk in Type 2 Diabetes Mellitus (T2DM) patients. We also tested the feasibility of using this App in clinical practice., Methods: Based on 2019 European Society of Cardiology/European Association for the Study of Diabetes criteria for cardiovascular risk stratification in T2DM, the AWARE App classifies patients into very high (VH
CVR ), high (HCVR ) and moderate (MCVR ) cardiovascular risk categories. In this retrospective clinical study, we employed the App to assess the cardiovascular risk of T2DM patients, while also collecting data about current glycaemic control and pharmacological treatment., Results: 2243 T2DM consecutive patients were evaluated. 72.2% of the patients were VHCVR , 8.9% were HCVR , 0.8% were MCVR while 18.2% did not fit into any of the risk categories and were classified as "moderate-to-high" (MHCVR ). Compared with the other groups, patients with VHCVD were more frequently ≥ 65 years old (68.9%), with a longer disease duration (≥ 10 years [56.8%]), a history of cardiovascular disease (41.4%), organ damage (35.5%) and a higher numbers of cardiovascular risk factors. Patients with MHCVD generally had disease duration < 10 years (96%), younger age (50-60 years [55%]), no history of cardiovascular disease, no organ damage, and 1-2 cardiovascular risk factors (89%). Novel drugs such as Glucagon Like Peptyde 1 Receptor Agonists or Sodium-Glucose Linked Transporter 2 inhibitors were prescribed only to 26.3% of the patients with VHCVR and to 24.7% of those with HCVR . Glycaemic control was unsatisfactory in this patients population (HbA1c 7.5 ± 3.4% [58.7 ± 13.4 mmol/mol])., Conclusions: The AWARE App proved to be a practical tool for cardiovascular risk stratification of T2DM patients in real-world clinical practice., (© 2023. The Author(s).) more...- Published
- 2023
- Full Text
- View/download PDF
64. SGLT2-inhibitors are effective and safe in the elderly: The SOLD study.
- Author
-
Lunati ME, Cimino V, Gandolfi A, Trevisan M, Montefusco L, Pastore I, Pace C, Betella N, Favacchio G, Bulgheroni M, Bucciarelli L, Massari G, Mascardi C, Girelli A, Morpurgo PS, Folli F, Luzi L, Mirani M, Pintaudi B, Bertuzzi F, Berra C, and Fiorina P more...
- Subjects
- Aged, Aged, 80 and over, Canagliflozin adverse effects, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents adverse effects, Patient Safety, Sodium-Glucose Transporter 2, Diabetes Mellitus, Type 2 drug therapy, Sodium-Glucose Transporter 2 Inhibitors adverse effects
- Abstract
Background and Aims: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) may have important benefits for the elderly with type 2 diabetes (T2D), however some safety concerns still limit their use in patients over 70 years of age. The SOLD study (SGLT2i in Older Diabetic patients) is a multicenter study, aimed to evaluate the effectiveness and safety of SGLT2i in the older diabetic patients in a real-life setting., Materials and Methods: We analyzed a population of 739 adults (mean age 75.4 ± 3.9 years, M/F 420/319) with T2D, which started a SGLT2i-based treatment after the age of 70, with at least one year of follow-up. Data were collected at baseline, at 6 and 12 months of follow-up., Results: SGLT2i (37.5% Empagliflozin, 35.7% Dapagliflozin, 26.1% Canagliflozin, 0.7% Ertugliflozin) were an add-on therapy to Metformin in 88.6%, to basal insulin in 36.1% and to other antidiabetic drugs in 29.6% of cases. 565 subjects completed the follow up, while 174 (23.5%) discontinued treatment due to adverse events which were SGLT2i related. A statistically significant reduction of glycated hemoglobin (baseline vs 12 months: 7.8 ± 1.1 vs 7.1 ± 0.8%, p < 0.001) and body mass index values (baseline vs 12 months: 29.2 ± 4.7 vs 28.1 ± 4.5 kg/m
2 , p < 0.001) were evident during follow-up. Overall, estimated glomerular filtration rate remained stable over time, with significant reduction of urinary albumin excretion. In the subgroup of patients which were ≥ 80 years, a significant improvement in glycated hemoglobin values without renal function alterations was evident. Overall discontinuation rate during the follow-up period was different across age groups, being urinary tract infections and worsening of renal function the most common cause., Conclusion: SGLT2i are well-tolerated and safe in the elderly and appear as an effective therapeutic option, though some caution is also suggested, especially in more fragile subjects., (Copyright © 2022. Published by Elsevier Ltd.) more...- Published
- 2022
- Full Text
- View/download PDF
65. Obesity and COVID-19: the ominous duet affecting the renin-angiotensin system.
- Author
-
Luzi L, Bucciarelli L, Ferrulli A, Terruzzi I, and Massarini S
- Subjects
- COVID-19 mortality, COVID-19 physiopathology, Humans, Kallikrein-Kinin System, Obesity mortality, Obesity physiopathology, Pandemics, COVID-19 complications, Obesity complications, Renin-Angiotensin System
- Abstract
The world population is facing a health challenge never seen since the Spanish influenza of one hundred years ago. During the last months, the scientific community has been debating on the potential harmful effect of angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin II receptor type 1 receptor blockers (AT1-receptor blockers, ARBs) during the COVID-19 pandemic. That is because the S spike protein of SARS-CoV viruses utilizes the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter alveolar epithelial cells. Obesity, often associated to type 2 Diabetes, was shown to worsen the prognosis of SARS-CoV-2 infection. Herein we discuss the complex interaction between the renin-angiotensin-aldosterone system (RAAS), its receptors, and the interaction with the Kallikrein-Kinin-system (KKS) and the potential activation of the coagulation cascade. Alteration of the equilibrium between the RAAS system and the KKS cascade may explain the frequent thromboembolic complications of COVID-19 mainly seen in obese and diabetic-obese patients. In contrast, angiotensin (1-7) contributes to maintaining a correct balance between RAAS and KKS system. Our conclusion is that the higher mortality rate in patients with obesity is linked to the alteration of RAS and RAS-KKS interaction consequent to SARS-CoV-2-cell entrance. At present, no data support the necessity of modifying ACEi or ARBs treatment in hypertensive patients. more...
- Published
- 2021
- Full Text
- View/download PDF
66. Use of Liraglutide in the Real World and Impact at 36 Months on Metabolic Control, Weight, Lipid Profile, Blood Pressure, Heart Rate, and Renal Function.
- Author
-
Rondinelli M, Rossi A, Gandolfi A, Saponaro F, Bucciarelli L, Adda G, Molinari C, Montefusco L, Specchia C, Chiara Rossi M, Scardapane M, Arosio M, and Genovese S
- Subjects
- Aged, Blood Pressure drug effects, Body Mass Index, Body Weight drug effects, Female, Glycated Hemoglobin metabolism, Heart Rate drug effects, Humans, Insulin therapeutic use, Italy, Lipids blood, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use
- Abstract
Purpose: An observational retrospective study was conducted by 2 diabetes clinics in Italy to assess patterns of use and long-term effectiveness of liraglutide on established and emerging parameters., Methods: Data from 261 patients with type 2 diabetes who started treatment with liraglutide between 2010 and 2014 were collected. Hierarchical linear regression models were applied to assess trends over time of clinical parameters. Factors associated with higher likelihood of dropout were identified through multivariate logistic analysis., Findings: Liraglutide was initiated as a switch in 42.5% of patients and as an add-on in 49.8%; in 7.7% of the patients initiation of liraglutide was associated with a reduction in the number of pharmacologic agents. A statistically significant reduction after 36 months was found for the following parameters (mean change [95% CIs]): glycosylated hemoglobin (HbA
1c ; -1.01% [1.34% to -0.68%]), fasting blood glucose (-27.5 [-40.6 to -14.4] mg/dL), weight (-2.9 [-4.5 to -1.3] kg), body mass index (-1.13 [-1.76 to -0.50] kg/m2 ), waist circumference (-1.74 [-3.85 to -0.37] cm), and LDL-C (-24.7 [-36.67 to -12.8] mg/dL). Improvements in systolic (-3.5 mm Hg) and diastolic (-2.3 mm Hg) blood pressures were observed at 24 months. Albuminuria was reduced by -16.6 mg/L during 36 months, although statistical significance was not reached. Glomerular filtration rate and heart rate were unchanged. Reductions in HbA1c between -0.6% and -1.3% were obtained in specific subgroups. Treatment was effective also in patients with >20 years of diabetes duration, although the likelihood of dropout was 6% higher for each additional year of disease duration (RR = 1.06; 95% CI, 1.01-1.12). The likelihood of dropout was almost four times higher for subjects treated with insulin (RR = 3.82; 95% CI, 1.22-11.96) and more than twice for those treated with sulfonylureas (RR = 2.39; 95% CI, 1.16-4.94) compared with patients not treated with these agents., Implications: Liraglutide used in routine clinical conditions maintains its effectiveness on metabolic control and weight after 3 years. Improvements in terms of metabolic control were found when liraglutide was used as both switch and add-on treatment. In addition, improvements were sustained when liraglutide replaced sulfonylureas or insulin. Diabetes duration had no impact on drug efficacy. Long-term benefits relative to blood pressure and LDL-C were also found, which could not be entirely explained by antihypertensive/lipid-lowering treatment intensification. No major effect on renal parameters was documented. Diabetes duration and some concomitant treatments were associated with a higher likelihood of liraglutide discontinuation. These data can contribute to improve appropriateness and cost-effectiveness profile of liraglutide., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.) more...- Published
- 2017
- Full Text
- View/download PDF
67. The protective effect of the Mediterranean diet on endothelial resistance to GLP-1 in type 2 diabetes: a preliminary report.
- Author
-
Ceriello A, Esposito K, La Sala L, Pujadas G, De Nigris V, Testa R, Bucciarelli L, Rondinelli M, and Genovese S
- Subjects
- Adult, Aged, Blood Glucose metabolism, Drug Resistance drug effects, Female, Humans, Inflammation drug therapy, Male, Middle Aged, Oxidative Stress drug effects, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 drug therapy, Diet, Mediterranean, Endothelium, Vascular drug effects, Glucagon-Like Peptide 1 metabolism, Hyperglycemia prevention & control
- Abstract
Background: In type 2 diabetes, acute hyperglycemia worsens endothelial function and inflammation,while resistance to GLP-1 action occurs. All these phenomena seem to be related to the generation of oxidative stress. A Mediterranean diet, supplemented with olive oil, increases plasma antioxidant capacity, suggesting that its implementation can have a favorable effect on the aforementioned phenomena. In the present study, we test the hypothesis that a Mediterranean diet using olive oil can counteract the effects of acute hyperglycemia and can improve the resistance of the endothelium to GLP-1 action., Methods: Two groups of type 2 diabetic patients, each consisting of twelve subjects, participated in a randomized trial for three months, following a Mediterranean diet using olive oil or a control low-fat diet. Plasma antioxidant capacity, endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels were evaluated at baseline and at the end of the study. The effect of GLP-1 during a hyperglycemic clamp, was also studied at baseline and at the end of the study., Results: Compared to the control diet, the Mediterranean diet increased plasma antioxidant capacity and improved basal endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels. The Mediterranean diet also reduced the negative effects of acute hyperglycemia, induced by a hyperglycemic clamp, on endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels. Furthermore, the Mediterranean diet improved the protective action of GLP-1 on endothelial function, nitrotyrosine, 8-iso-PGF2a, IL-6 and ICAM-1 levels, also increasing GLP-1-induced insulin secretion., Conclusions: These data suggest that the Mediterranean diet, using olive oil, prevents the acute hyperglycemia effect on endothelial function, inflammation and oxidative stress, and improves the action of GLP-1, which may have a favorable effect on the management of type 2 diabetes, particularly for the prevention of cardiovascular disease. more...
- Published
- 2014
- Full Text
- View/download PDF
68. Direct separation of the enantiomers of oxaliplatin on a cellulose-based chiral stationary phase in hydrophilic interaction liquid chromatography mode.
- Author
-
Gallinella B, Bucciarelli L, Zanitti L, Ferretti R, and Cirilli R
- Subjects
- Carbamates, Chromatography, Liquid methods, Hydrophobic and Hydrophilic Interactions, Oxaliplatin, Stereoisomerism, Temperature, Antineoplastic Agents isolation & purification, Cellulose analogs & derivatives, Organoplatinum Compounds isolation & purification
- Abstract
(R,R)-oxaliplatin is an anticancer enantiopure active pharmaceutical ingredient. Little attention has been devoted to the analysis of its enantiomeric composition. The enantioselective HPLC method reported in the current Pharmacopoeias shows clear disadvantages with regard to the low resolution and long elution times. In this work, it has been proven the applicability of a last generation polysaccharide-based chiral stationary phase (CSP), i.e. the Chiralpak IC-3, in the enantioseparation of oxaliplatin. Experimental results demonstrated the benefits arising from the development of enantioselective hydrophilic interaction liquid chromatography (HILIC) based strategies. A baseline separation with resolution factor of 5.8 was achieved using a 100mm×4.6mm I.D. IC-3 column set at the temperature of 40°C and a mobile phase consisting of acetonitrile-water 100:5 mixture. At a flow rate of 1mLmin(-1) the separation was completed within 8min. The optimized method was proven to be sensitive with LOD and LOQ of the enantiomeric impurity of 0.07 and 0.21μgmL(-1), respectively., (Copyright © 2014 Elsevier B.V. All rights reserved.) more...
- Published
- 2014
- Full Text
- View/download PDF
69. Peripheral venous congestion causes inflammation, neurohormonal, and endothelial cell activation.
- Author
-
Colombo PC, Onat D, Harxhi A, Demmer RT, Hayashi Y, Jelic S, LeJemtel TH, Bucciarelli L, Kebschull M, Papapanou P, Uriel N, Schmidt AM, Sabbah HN, and Jorde UP
- Subjects
- Adult, Angiotensin II metabolism, Arm blood supply, Cytokines metabolism, Female, Healthy Volunteers, Humans, Male, Neuropeptides metabolism, RNA, Messenger metabolism, Vascular Cell Adhesion Molecule-1 metabolism, Endothelial Cells metabolism, Endothelium, Vascular metabolism, Heart Failure etiology, Hyperemia physiopathology, Neurotransmitter Agents metabolism, Vasculitis etiology
- Abstract
Aims: Volume overload and venous congestion are typically viewed as a consequence of advanced and of acute heart failure (HF) and renal failure (RF) although it is possible that hypervolaemia itself might be a critical intermediate in the pathophysiology of these diseases. This study aimed at elucidating whether peripheral venous congestion is sufficient to promote changes in inflammatory, neurohormonal, and endothelial phenotype similar to those observed in HF and RF., Methods: To experimentally model peripheral venous congestion, we developed a new method (so-called venous stress test) and applied the methodology on 24 healthy subjects (14 men, age 35 ± 2 years). Venous arm pressure was increased to ∼30 mmHg above the baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 min of venous congestion, using angiocatheters and endovascular wires. Magnetic beads coated with EC-specific antibodies were used for EC separation; amplified mRNA was analysed by Affymetrix HG-U133 Plus 2.0 Microarray., Results: Plasma interleukin-6 (IL-6), endothelin-1 (ET-1), angiotensin II (AII), vascular cell adhesion molecule-1 (VCAM-1), and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. A total of 3437 mRNA probe sets were differentially expressed (P < 0.05) in venous ECs before vs. after testing, including ET-1, VCAM-1, and CXCL2., Conclusion: Peripheral venous congestion causes release of inflammatory mediators, neurohormones, and activation of ECs. Overall, venous congestion mimicked, notable aspects of the phenotype typical of advanced and of acute HF and RF. more...
- Published
- 2014
- Full Text
- View/download PDF
70. Vitamin C further improves the protective effect of glucagon-like peptide-1 on acute hypoglycemia-induced oxidative stress, inflammation, and endothelial dysfunction in type 1 diabetes.
- Author
-
Ceriello A, Novials A, Ortega E, Canivell S, La Sala L, Pujadas G, Bucciarelli L, Rondinelli M, and Genovese S
- Subjects
- Acute Disease, Antioxidants therapeutic use, Blood Glucose metabolism, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 physiopathology, Dose-Response Relationship, Drug, Drug Therapy, Combination, Endothelium, Vascular physiopathology, Female, Follow-Up Studies, Humans, Hypoglycemia blood, Hypoglycemia chemically induced, Hypoglycemic Agents adverse effects, Hypoglycemic Agents therapeutic use, Incretins therapeutic use, Inflammation blood, Infusions, Intravenous, Insulin adverse effects, Insulin therapeutic use, Male, Vasodilation drug effects, Young Adult, Ascorbic Acid administration & dosage, Diabetes Mellitus, Type 1 drug therapy, Endothelium, Vascular drug effects, Glucagon-Like Peptide 1 administration & dosage, Hypoglycemia drug therapy, Inflammation prevention & control, Oxidative Stress drug effects
- Abstract
Objective: To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1 diabetes., Research Design and Methods: A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced., Results: At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced., Conclusions: This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress. more...
- Published
- 2013
- Full Text
- View/download PDF
71. Vitamin C further improves the protective effect of GLP-1 on the ischemia-reperfusion-like effect induced by hyperglycemia post-hypoglycemia in type 1 diabetes.
- Author
-
Ceriello A, Novials A, Ortega E, Canivell S, Pujadas G, La Sala L, Bucciarelli L, Rondinelli M, and Genovese S
- Subjects
- Adult, Biomarkers blood, Blood Glucose metabolism, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 physiopathology, Dinoprost analogs & derivatives, Dinoprost blood, Female, Humans, Hyperglycemia blood, Hyperglycemia diagnosis, Hyperglycemia physiopathology, Hypoglycemia blood, Hypoglycemia diagnosis, Hypoglycemia physiopathology, Inflammation blood, Inflammation prevention & control, Inflammation Mediators blood, Infusions, Parenteral, Intercellular Adhesion Molecule-1 blood, Interleukin-6 blood, Male, Oxidative Stress drug effects, Reperfusion Injury blood, Reperfusion Injury diagnosis, Reperfusion Injury physiopathology, Time Factors, Treatment Outcome, Tyrosine analogs & derivatives, Tyrosine blood, Vasodilation drug effects, Young Adult, Antioxidants administration & dosage, Ascorbic Acid administration & dosage, Blood Glucose drug effects, Diabetes Mellitus, Type 1 drug therapy, Glucagon-Like Peptide 1 administration & dosage, Hyperglycemia drug therapy, Hypoglycemia drug therapy, Hypoglycemic Agents administration & dosage, Reperfusion Injury prevention & control
- Abstract
Background: It has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested., Methods: 15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured., Results: After 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia., Conclusions: This study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition. more...
- Published
- 2013
- Full Text
- View/download PDF
72. Decreased plasma soluble RAGE in patients with hypercholesterolemia: effects of statins.
- Author
-
Santilli F, Bucciarelli L, Noto D, Cefalù AB, Davì V, Ferrante E, Pettinella C, Averna MR, Ciabattoni G, and Davì G
- Subjects
- Anticholesteremic Agents blood, Anticholesteremic Agents therapeutic use, Arginine analogs & derivatives, Arginine blood, Atherosclerosis blood, Atherosclerosis drug therapy, Atorvastatin, Cross-Sectional Studies, Dinoprost analogs & derivatives, Dinoprost blood, Dinoprost urine, Double-Blind Method, Female, Heptanoic Acids blood, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia urine, Male, Middle Aged, Nitric Oxide biosynthesis, Nitric Oxide Synthase antagonists & inhibitors, Nitric Oxide Synthase metabolism, Pravastatin blood, Pyrroles blood, Receptor for Advanced Glycation End Products, Heptanoic Acids therapeutic use, Hypercholesterolemia blood, Hypercholesterolemia drug therapy, Pravastatin therapeutic use, Pyrroles therapeutic use, Receptors, Immunologic blood
- Abstract
The receptor for advanced glycation endproducts (RAGE) is overexpressed at sites of vascular pathology. A soluble RAGE isoform (sRAGE) neutralizes the ligand-mediated damage by acting as a decoy. We hypothesized that in hypercholesterolemia up-regulation of the ligand-RAGE axis may bridge impairment of nitric oxide biosynthesis with oxidative stress. We measured in 60 hypercholesterolemic patients and 20 controls plasma total sRAGE levels, urinary 8-iso-prostaglandin (PG) F(2alpha) excretion, and plasma levels of asymmetric dimethylarginine (ADMA). The effects of two structurally different statins (pravastatin and atorvastatin) on these parameters were analyzed in 20 hypercholesterolemic subjects free of vascular disease. Plasma sRAGE was significantly lower, ADMA and urinary 8-iso-PGF(2alpha) were higher, in hypercholesterolemic versus normocholesterolemic patients. Patients on statin treatment with previous myocardial infarction had lower 8-iso-PGF(2alpha), higher sRAGE, and unchanged ADMA levels compared to subjects free of vascular disease. On multivariate regression analysis only 8-iso-PGF(2alpha) and ADMA predicted sRAGE levels. An 8-week treatment with either statin was associated with a significant reduction in urinary 8-iso-PGF(2alpha), whereas only atorvastatin raised sRAGE levels near to normal values, with no change in ADMA levels. sRAGE might serve as an endogenous protecting factor for accelerated atherosclerosis mediated by oxidative stress and endothelial dysfunction in hypercholesterolemia. more...
- Published
- 2007
- Full Text
- View/download PDF
73. Soluble RAGE in type 2 diabetes: association with oxidative stress.
- Author
-
Devangelio E, Santilli F, Formoso G, Ferroni P, Bucciarelli L, Michetti N, Clissa C, Ciabattoni G, Consoli A, and Davì G
- Subjects
- Arginine analogs & derivatives, Arginine blood, Arginine drug effects, Cross-Sectional Studies, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Diabetic Angiopathies blood, Diabetic Angiopathies metabolism, Dinoprost analogs & derivatives, Dinoprost urine, Enzyme-Linked Immunosorbent Assay, Female, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents therapeutic use, Male, Middle Aged, Oxidative Stress drug effects, Receptor for Advanced Glycation End Products, Receptors, Immunologic drug effects, Diabetes Mellitus, Type 2 blood, Oxidative Stress physiology, Receptors, Immunologic blood
- Abstract
Advanced glycation end products (AGEs) contribute to diabetic vascular complications by engaging the AGE receptor (RAGE). A soluble RAGE form (sRAGE) acts as a decoy domain receptor, thus decreasing AGE cellular binding. A cross-sectional comparison of sRAGE, asymmetric dimethylarginine (ADMA) plasma levels (index of endothelial dysfunction), and urinary 8-iso-prostaglandin (PG)F(2alpha) (marker of oxidative stress) was performed between 86 diabetic patients and 43 controls. Plasma sRAGE levels were significantly lower and ADMA levels were significantly higher in diabetic patients as compared to controls (P<0.0001). HbA1c and urinary 8-iso-PGF(2alpha) were correlated inversely with sRAGE and directly with ADMA. On multivariate analysis HbA1c was independently related to sRAGE levels in diabetic patients. Twenty-four of 86 patients with newly diagnosed diabetes and 12 patients in poor metabolic control were reevaluated after treatment with a hypoglycemic agent or insulin, respectively. Improvement in metabolic control by oral agents or insulin resulted in a significant increase in sRAGE and decrease in ADMA levels (P<0.0001). Thus, poor glycemic control reduces sRAGE levels, in association with enhanced oxidative stress and endothelial dysfunction in diabetes. These abnormalities are susceptible to modulation by improvement in metabolic control. more...
- Published
- 2007
- Full Text
- View/download PDF
74. RAGE modulates vascular inflammation and atherosclerosis in a murine model of type 2 diabetes.
- Author
-
Wendt T, Harja E, Bucciarelli L, Qu W, Lu Y, Rong LL, Jenkins DG, Stein G, Schmidt AM, and Yan SF
- Subjects
- Animals, Aorta, Thoracic metabolism, Aorta, Thoracic pathology, Arteritis metabolism, Arteritis prevention & control, Atherosclerosis metabolism, Atherosclerosis prevention & control, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Type 2 complications, Glycation End Products, Advanced administration & dosage, Glycation End Products, Advanced metabolism, Immunoblotting, Male, Mice, Mice, Inbred C57BL, Receptor for Advanced Glycation End Products, Receptors, Immunologic metabolism, Treatment Outcome, Vascular Cell Adhesion Molecule-1 metabolism, Arteritis etiology, Atherosclerosis etiology, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Type 2 metabolism, Receptors, Immunologic administration & dosage
- Abstract
Previous studies demonstrated that induction of diabetes with streptozotocin (stz) accelerated atherosclerosis in hyperlipidemic apo E null (-/-) mice. Blockade of the Receptor for Advanced Glycation Endproducts (RAGE) in those animals suppressed acceleration of atherosclerotic lesion area, in a manner independent of changes in levels of glucose, insulin or lipids. In the present studies, we extended these concepts to a murine model of type 2 diabetes, and bred apo E -/- mice into the db/db background. Db/db mice are a model of obesity and insulin resistance-mediated hyperglycemia. Compared to apo E -/- m/db (non-diabetic) mice, apo E -/- db/db (diabetic) mice displayed accelerated atherosclerosis at the aortic sinus. Consistent with an important role for RAGE in this process, administration of soluble (s) RAGE, the extracellular ligand-binding domain of RAGE, resulted in significantly reduced atherosclerotic lesion area in a glycemia- and lipid-independent manner. In parallel, apo E -/- db/db mice displayed RAGE-dependent enhanced expression of Vascular Cell Adhesion Molecule-1, tissue factor and matrix metalloproteinase (MMP)-9 antigen/activity in aortae compared to non-diabetic animals. In addition, consistent with the premise that upregulation of RAGE ligands and RAGE occurs even in the non-diabetic, hyperlipidemic state, albeit to lesser degrees than in diabetes, administration of sRAGE to apo E -/- m/db mice resulted in decreased atherosclerotic lesion area at the aortic sinus. Taken together, these findings establish a new murine model for the study of atherosclerosis in type 2 diabetes and highlight important roles for RAGE in proatherogenic mechanisms in hyperglycemia triggered by insulin resistance. more...
- Published
- 2006
- Full Text
- View/download PDF
75. Aldose reductase and AGE-RAGE pathways: key players in myocardial ischemic injury.
- Author
-
Kaneko M, Bucciarelli L, Hwang YC, Lee L, Yan SF, Schmidt AM, and Ramasamy R
- Subjects
- Animals, Cardiovascular Diseases physiopathology, Diabetic Angiopathies physiopathology, Humans, Myocardial Ischemia etiology, Receptor for Advanced Glycation End Products, Aldehyde Reductase physiology, Glycation End Products, Advanced physiology, Myocardial Ischemia physiopathology, Receptors, Immunologic physiology
- Abstract
Cardiovascular disease represents the major cause of morbidity and mortality in patients with diabetes mellitus. The impact of cardiac disease includes increased sensitivity of diabetic myocardium to ischemic episodes and diabetic cardiomyopathy, manifested as a subnormal functional response of the diabetic heart independent of coronary artery disease. In this context, we were to our knowledge the first to demonstrate that diabetes increases glucose flux via the first and key enzyme, aldose reductase, of the polyol pathway, resulting in impaired glycolysis under normoxic and ischemic conditions in diabetic myocardium. Our laboratory has been investigating the role of the polyol pathway in mediating myocardial ischemic injury in diabetics. Furthermore, the influence of the aldose reductase pathway in facilitating generation of key potent glycating compounds has led us to investigate the impact of advanced glycation end products (AGEs) in myocardial ischemic injury in diabetics. The potent impact of increased flux via the aldose reductase pathway and the increased AGE interactions with its receptor (RAGE) resulting in cardiac dysfunction will be discussed in this chapter. more...
- Published
- 2005
- Full Text
- View/download PDF
76. Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice.
- Author
-
Lalla E, Lamster IB, Hofmann MA, Bucciarelli L, Jerud AP, Tucker S, Lu Y, Papapanou PN, and Schmidt AM
- Subjects
- Alveolar Bone Loss, Animals, Apolipoproteins E genetics, Arteriosclerosis blood, Arteriosclerosis diagnosis, Cholesterol blood, Mice, Mice, Inbred C57BL, Mice, Knockout, Triglycerides blood, Arteriosclerosis microbiology, Bacteroidaceae Infections complications, Periodontitis complications, Porphyromonas gingivalis
- Abstract
Objective: Because recent epidemiologic evidence suggests that periodontal infections may increase the risk of atherosclerosis and related events in humans, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on atherogenesis in hypercholesterolemic apolipoprotein E-null mice., Methods and Results: In the absence of alterations in distinct risk factors, P gingivalis infection exacerbated the early stages of atherogenesis in this model. Infected animals displayed evidence of local periodontal infection, as the severity of alveolar bone loss, the hallmark of periodontitis, was increased. Generalized activation of host inflammatory responses was evident in infected mice, as demonstrated by serum IgG response to P gingivalis and elevated levels of interleukin-6. P gingivalis DNA was localized in the aortic tissue from a limited number of infected mice but not in any noninfected controls. Infected mice displayed enhanced vascular activation, as suggested by increased aortic expression of vascular cell adhesion molecule-1 and tissue factor., Conclusions: Oral infection with P gingivalis accelerates early atherosclerosis. Thus, uncovering the underlying mechanisms is critical for the design of preventive and therapeutic strategies targeting atherosclerotic vascular disease and its sequelae. more...
- Published
- 2003
- Full Text
- View/download PDF
77. Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: insights into the pathogenesis of macrovascular complications in diabetes.
- Author
-
Wendt T, Bucciarelli L, Qu W, Lu Y, Yan SF, Stern DM, and Schmidt AM
- Subjects
- Animals, Arteriosclerosis chemically induced, Arteriosclerosis immunology, Diabetes Mellitus immunology, Diabetic Angiopathies immunology, Humans, Inflammation complications, Leukocyte L1 Antigen Complex metabolism, Ligands, Membrane Proteins metabolism, Mice, Models, Animal, Rats, Receptor for Advanced Glycation End Products, S100 Proteins metabolism, Signal Transduction physiology, Vascular Diseases chemically induced, Arteriosclerosis metabolism, Diabetes Mellitus physiopathology, Diabetic Angiopathies metabolism, Glycation End Products, Advanced metabolism, Inflammation metabolism, Receptors, Immunologic metabolism, Vascular Diseases metabolism
- Abstract
The incidence and severity of atherosclerosis is increased in patients with diabetes. Indeed, accelerated macrovascular disease in diabetic patients has emerged as a leading cause of morbidity and mortality in the United States and worldwide. Multiple investigations have suggested that there are numerous potential contributory factors that underlie these observations. Our laboratory has focused on the contribution of receptor for advanced glycation endproducts (RAGE) and its proinflammatory ligands, advanced glycation endproducts (AGEs) and S100/calgranulins in vascular perturbation, manifested as enhanced atherogenesis or accelerated restenosis after angioplasty. In rodent models of diabetic complications, blockade of RAGE suppressed vascular hyperpermeability, accelerated atherosclerotic lesion area and complexity in diabetic apolipoprotein E-deficient mice, and prevented exaggerated neointimal formation in hyperglycemic fatty Zucker rats subjected to injury of the carotid artery. In this review, we summarize these findings and provide an overview of distinct mechanisms that contribute to the development of accelerated diabetic macrovascular disease. Insights into therapeutic strategies to prevent or interrupt these processes are presented. more...
- Published
- 2002
- Full Text
- View/download PDF
78. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice.
- Author
-
Goova MT, Li J, Kislinger T, Qu W, Lu Y, Bucciarelli LG, Nowygrod S, Wolf BM, Caliste X, Yan SF, Stern DM, and Schmidt AM
- Subjects
- Animals, Becaplermin, Binding Sites, Cytokines biosynthesis, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 pathology, Endothelial Growth Factors metabolism, Gene Expression Regulation, Granuloma pathology, Granuloma physiopathology, Lymphokines metabolism, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 3 metabolism, Matrix Metalloproteinase 9 metabolism, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Models, Biological, Neovascularization, Physiologic, Platelet-Derived Growth Factor metabolism, Proto-Oncogene Proteins c-sis, Receptor for Advanced Glycation End Products, Receptors, Immunologic antagonists & inhibitors, Time Factors, Tumor Necrosis Factor-alpha biosynthesis, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Wound Healing genetics, Wounds and Injuries physiopathology, Diabetes Mellitus, Type 1 physiopathology, Glycation End Products, Advanced physiology, Receptors, Immunologic physiology, Receptors, Immunologic therapeutic use, Wound Healing physiology, Wounds and Injuries pathology
- Abstract
Receptor for advanced glycation end-products (RAGE), and two of its ligands, AGE and EN-RAGEs (members of the S100/calgranulin family of pro-inflammatory cytokines), display enhanced expression in slowly resolving full-thickness excisional wounds developed in genetically diabetic db+/db+ mice. We tested the concept that blockade of RAGE, using soluble(s) RAGE, the extracellular ligand-binding domain of the receptor, would enhance wound closure in these animals. Administration of sRAGE accelerated the development of appropriately limited inflammatory cell infiltration and activation in wound foci. In parallel with accelerated wound closure at later times, blockade of RAGE suppressed levels of cytokines; tumor necrosis factor-alpha; interleukin-6; and matrix metalloproteinases-2, -3, and -9. In addition, generation of thick, well-vascularized granulation tissue was enhanced, in parallel with increased levels of platelet-derived growth factor-B and vascular endothelial growth factor. These findings identify a central role for RAGE in disordered wound healing associated with diabetes, and suggest that blockade of this receptor might represent a targeted strategy to restore effective wound repair in this disorder. more...
- Published
- 2001
- Full Text
- View/download PDF
79. Receptor for advanced glycation end products mediates inflammation and enhanced expression of tissue factor in vasculature of diabetic apolipoprotein E-null mice.
- Author
-
Kislinger T, Tanji N, Wendt T, Qu W, Lu Y, Ferran LJ Jr, Taguchi A, Olson K, Bucciarelli L, Goova M, Hofmann MA, Cataldegirmen G, D'Agati V, Pischetsrieder M, Stern DM, and Schmidt AM
- Subjects
- Animals, Aorta metabolism, Kidney metabolism, Leukocyte L1 Antigen Complex, Male, Membrane Glycoproteins metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B metabolism, Neural Cell Adhesion Molecules metabolism, Receptor for Advanced Glycation End Products, Vascular Cell Adhesion Molecule-1 metabolism, Vasculitis complications, Apolipoproteins E genetics, Diabetes Mellitus, Experimental complications, Receptors, Immunologic physiology, Thromboplastin biosynthesis, Vasculitis metabolism
- Abstract
Advanced glycation end products (AGEs) and their cell surface receptor, RAGE, have been implicated in the pathogenesis of diabetic complications. Here, we studied the role of RAGE and expression of its proinflammatory ligands, EN-RAGEs (S100/calgranulins), in inflammatory events mediating cellular activation in diabetic tissue. Apolipoprotein E-null mice were rendered diabetic with streptozotocin at 6 weeks of age. Compared with nondiabetic aortas and kidneys, diabetic aortas and kidneys displayed increased expression of RAGE, EN-RAGEs, and 2 key markers of vascular inflammation, vascular cell adhesion molecule (VCAM)-1 and tissue factor. Administration of soluble RAGE, the extracellular domain of the receptor, or vehicle to diabetic mice for 6 weeks suppressed levels of VCAM-1 and tissue factor in the aorta, in parallel with decreased expression of RAGE and EN-RAGEs. Diabetic kidney demonstrated increased numbers of EN-RAGE-expressing inflammatory cells infiltrating the glomerulus and enhanced mRNA for transforming growth factor-beta, fibronectin, and alpha(1) (IV) collagen. In mice treated with soluble RAGE, the numbers of infiltrating inflammatory cells and mRNA levels for these glomerular cytokines and components of extracellular matrix were decreased. These data suggest that activation of RAGE primes cells targeted for perturbation in diabetic tissues by the induction of proinflammatory mediators. more...
- Published
- 2001
- Full Text
- View/download PDF
80. Monilial sepsis in the surgical patient.
- Author
-
Richards KE, Pierson CL, Bucciarelli L, and Feller I
- Subjects
- Adolescent, Adult, Aged, Ampicillin adverse effects, Body Temperature, Burns microbiology, Candida albicans isolation & purification, Candidiasis microbiology, Candidiasis urine, Carbenicillin adverse effects, Catheterization adverse effects, Child, Child, Preschool, Chloramphenicol adverse effects, Erythromycin adverse effects, Female, Gentamicins adverse effects, Humans, Infant, Kanamycin adverse effects, Male, Middle Aged, Nasopharynx microbiology, Penicillin Resistance, Penicillins adverse effects, Polymyxins adverse effects, Tetracycline adverse effects, Urinary Catheterization adverse effects, Wound Infection microbiology, Burns complications, Candidiasis etiology, Sepsis etiology, Surgical Procedures, Operative
- Published
- 1972
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.