28 research outputs found
Role of galectin-3 as a receptor for advanced glycosylation end products
Role of galectin-3 as a receptor for advanced glycosylation end products. The advanced glycosylation end product (AGE)-binding proteins identified so far include the components of the AGE-receptor complex p60, p90 and galectin-3, receptor for advanced glycosylation end products (RAGE), and the macrophage scavenger receptor types I and II. Galectin-3 interacts with β-galactoside residues of several cell surface and matrix glycoproteins through the carbohydrate recognition domain and is also capable of peptide–peptide associations mediated by its N-terminus domain. These structural properties enable galectin-3 to exert multiple functions, including the modulation of cell adhesion, the control of cell cycle, and the mRNA splicing activity. Moreover, in macrophages, astrocytes, and endothelial cells, galectin-3 has been shown to exhibit a high-affinity binding for AGEs; the lack of a transmembrane anchor sequence or signal peptide suggests that it associates with other AGE-receptor components rather than playing an independent role as AGE-receptor. In tissues that are targets of diabetic vascular complications, such as the mesangium and the endothelium, galectin-3 is not expressed or only weakly expressed under basal conditions, at variance with p90 and p60 but becomes detectable with aging and is induced or up-regulated by the diabetic milieu, which only slightly affects the expression of p90 or p60. This (over)expression of galectin-3 may in turn modulate AGE-receptor-mediated events by modifying the function of the AGE-receptor complex, which could play a role in the pathogenesis of target tissue injury. Up-regulated galectin-3 expression may also exert direct effects on tissue remodeling, independently of AGE ligands, by virtue of its adhesive and growth regulating properties
The European Research Infrastructures of the ESFRI Roadmap in Biological and Medical Sciences: status and perspectives
Introduction. Since 2002, the European Strategy Forum on Research Infrastructures identified the needs for Research Infrastructures (RIs) in Europe in priority fields of scientific research and drafted a strategic document, the ESFRI Roadmap, defining the specific RIs essential to foster European research and economy. The Biological and Medical Sciences RIs (BMS RIs) were developed thanks to the active participation of many institutions in different European member states associated to address the emerging needs in biomedicine and, among these, the Italian National Institute of Health (ISS), in virtue of its role in public health and research, has been specifically involved in the national development and implementation of three RIs: the Biobanking and Biomolecu-lar Resources Research Infrastructure (BBMRI), the European Advanced Translational Research Infrastructure in Medicine (EATRIS) and the European Clinical Research Infrastructures Network (ECRIN). Aim. This article outlines the design and development of these RIs up to the recent achievement of the ERIC status, their importance in the Horizon 2020 programme and their societal and economic potential impact, with special attention to their development and significance in Italy. Conclusions. The ISS plays a unique role in fostering a coordinated participation of excellence Italian institutes/facilities to different European biomedical RIs, thus contributing to health innovation, healthcare optimization, and healthcare cost containment.
The Burden of Type 1 and Type 2 Diabetes Among Adolescents and Young Adults in 24 Western European Countries, 1990–2019: Results From the Global Burden of Disease Study 2019
Objectives: As little is known about the burden of type 1 (T1DM) and type 2 diabetes (T2DM) in adolescents in Western Europe (WE), we aimed to explore their epidemiology among 10–24 year-olds.Methods: Estimates were retrieved from the Global Burden of Diseases Study (GBD) 2019. We reported counts, rates per 100,000 population, and percentage changes from 1990 to 2019 for prevalence, incidence and years lived with disability (YLDs) of T1DM and T2DM, and the burden of T2DM in YLDs attributable to high body mass index (HBMI), for 24 WE countries.Results: In 2019, prevalence and disability estimates were higher for T1DM than T2DM among 10–24 years old adolescents in WE. However, T2DM showed a greater increase in prevalence and disability than T1DM in the 30 years observation period in all WE countries. Prevalence increased with age, while only minor differences were observed between sexes.Conclusion: Our findings highlight the substantial burden posed by DM in WE among adolescents. Health system responses are needed for transition services, data collection systems, education, and obesity prevention
The Burden of Type 1 and Type 2 Diabetes Among Adolescents and Young Adults in 24 Western European Countries, 1990–2019:Results From the Global Burden of Disease Study 2019
Objectives: As little is known about the burden of type 1 (T1DM) and type 2 diabetes (T2DM) in adolescents in Western Europe (WE), we aimed to explore their epidemiology among 10–24 year-olds. Methods: Estimates were retrieved from the Global Burden of Diseases Study (GBD) 2019. We reported counts, rates per 100,000 population, and percentage changes from 1990 to 2019 for prevalence, incidence and years lived with disability (YLDs) of T1DM and T2DM, and the burden of T2DM in YLDs attributable to high body mass index (HBMI), for 24 WE countries. Results: In 2019, prevalence and disability estimates were higher for T1DM than T2DM among 10–24 years old adolescents in WE. However, T2DM showed a greater increase in prevalence and disability than T1DM in the 30 years observation period in all WE countries. Prevalence increased with age, while only minor differences were observed between sexes. Conclusion: Our findings highlight the substantial burden posed by DM in WE among adolescents. Health system responses are needed for transition services, data collection systems, education, and obesity prevention.</p
The Burden of Type 1 and Type 2 Diabetes Among Adolescents and Young Adults in 24 Western European Countries, 1990–2019:Results From the Global Burden of Disease Study 2019
Objectives: As little is known about the burden of type 1 (T1DM) and type 2 diabetes (T2DM) in adolescents in Western Europe (WE), we aimed to explore their epidemiology among 10–24 year-olds. Methods: Estimates were retrieved from the Global Burden of Diseases Study (GBD) 2019. We reported counts, rates per 100,000 population, and percentage changes from 1990 to 2019 for prevalence, incidence and years lived with disability (YLDs) of T1DM and T2DM, and the burden of T2DM in YLDs attributable to high body mass index (HBMI), for 24 WE countries. Results: In 2019, prevalence and disability estimates were higher for T1DM than T2DM among 10–24 years old adolescents in WE. However, T2DM showed a greater increase in prevalence and disability than T1DM in the 30 years observation period in all WE countries. Prevalence increased with age, while only minor differences were observed between sexes. Conclusion: Our findings highlight the substantial burden posed by DM in WE among adolescents. Health system responses are needed for transition services, data collection systems, education, and obesity prevention.</p
Meccanismi patogenetici delle complicanze microvascolari del diabete: studi in modelli sperimentali in vivo e in vitro
Dottorato di ricerca in scienze endocrinologiche e metaboliche. 10. cicloConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal
Practical tools to identify short children born small-for-gestational-age eligible for rhGH treatment according to Italian regulation
Recombinant human growth hormone (rhGH) is an approved and effective treatment for short children born small for gestational age (SGA). Prevalence of children eligible for treatment as SGA is reported to be 1:1800. The latest data from the National Registry of Growth Hormone therapy (RNAOC) showed that the number of children treated with SGA indication is still small (prevalence 0.37/100,000) and these children are significantly less reported than those treated for growth hormone deficiency (GHD), although GHD prevalence is 1:4000-1:10,000. This means that many short children born SGA are still not properly identified, and therefore not treated with rhGH, or misdiagnosed as GHD. This article provides some practical tools for the identification of children eligible for rhGH treatment
HIGH GLUCOSE INHIBITS CYTOSOLIC CALCIUM SIGNALING IN CULTURED RAT MESANGIAL CELLS
Glomerular vasodilatation in the early stages of type I diabetes mellitus apparently results from arteriolar insensitivity to vasoconstrictors. Since cytosolic free calcium ([Ca2+]i) is a major signaling mechanism for smooth muscle contraction, we studied whether growth of smooth muscle-like rat glomerular mesangial cells in media with high glucose concentration affects [Ca2+]i responses to vasoconstrictors. In cells grown for five days in 22 mM glucose, we observed blunted responsiveness to three structurally unrelated vasoconstrictors that elevate [Ca2+]i via a phospholipase C-dependent mechanism, angiotensin II, prostaglandin F2 alpha, and arginine vasopressin. Inhibition of [Ca2+]i responses was not due to an osmotic effect of high glucose, since it was not mimicked by hypertonic mannitol. While the size of intracellular Ca2+ pools was unaffected by elevated glucose, Na+/Ca2+ exchange was markedly inhibited, thus ruling out both impaired filling of Ca2+ stores and enhanced counter-regulatory mechanisms. Impaired myoinositol transport or intracellular sorbitol accumulation were not responsible for the effects of high glucose, since supplementation of media with myo-inositol or with the aldose reductase inhibitor. Alcon 1576, failed to reverse insensitivity to vasoconstrictors. On the other hand, down-regulation or pharmacological inhibition of protein kinase C completely reversed the effects of high glucose, thus indicating involvement of this signal transduction pathway. These data suggest a possible intracellular mechanism for the impaired vascular sensitivity underlying early renal hemodynamic changes in diabetes mellitus
Glomerular Cell Replication and Cell Loss through Apoptosis in Experimental Diabetes mellitus
Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview
Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conducted in vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabetic milieu on retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight