Conjugation strategies of insulin to nanogels: new hope for nanogels Alzheimer's disease therapy?

Misdiagnosis of familial Mediterranean fever in patients with Anderson-Fabry disease

Fabry disease (FD) is an underdiagnosed pathology due to its symptomatology that overlaps with various systemic and rheumatic disorders, including familial Mediterranean fever (FMF). We examined the Mediterranean fever (MEFV) and α-galactosidase A (GLA) genes, whose mutations are responsible for FMF and FD, respectively, in 42 unrelated patients diagnosed with FMF, which revealed significant ambiguity regarding some of the symptoms which are also present in FD. The objective of this study was to determine the spectrum of mutations present in these genes, in order to identify cases of mistaken diagnosis of FMF and/or missed diagnosis of FD. Ten out of 42 patients had one mutation in homozyg…

Insulin Nanogels: a New Strategy for the Treatment of Alzheimer’s Disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD) degeneration. Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for AD. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation was chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility of the naked c…

Social closeness,salivary hormones and physical exercise

Introduction: Saliva collection and analysis is quickly becoming a useful and non-invasive tool for the evaluation of sport biomarkers. The aim of this study is to create a multidisciplinary assessment model, which can help to provide psychological and physiological responses, related to sport performances, social closeness and performance anxiety management in team sports. Materials and methods: We enrolled in our research 26 female volleyball players aged 13 ± 1 years old of three different teams (T1: 12 players; T2: 9 players; T3: 5 players). Saliva collection was carried out before and after the match for every team. Then we analyzed cortisol and progesterone concentrations through Elis…

Biomarkers of aging

Aging is a complex process that negatively impacts the development of the different systems and its ability to function. Moreover, the Aging rate in humans is not the same, principally due to genetic heterogeneity and environmental factors. The aging rate is measured as the decline of functional capacity and stress resistance. Therefore, several attempts have been made to analyse the individual age, ( so-called biological age) compared to chronological age. The biomarkers of aging are age-related body function or composition, these markers aim to assess the biological age and predict the onset of age-related diseases and/or residual lifetime. Such biomarkers should help in one hand to chara…

INTEGRATIVE APPROACH BETWEEN GENE VARIANTS, NEUROENDOCRINE EFFECTORS AND ANXIETY RESPONSE: A PILOT STUDY

The aim of this study is to investigate the neurobiology of stress/emotionality, creating a multidisciplinary assessment model, which can help to provide psychological and physiological responses depending on the genetic background related to sport performances, social closeness and performance anxiety management in team sports. We enrolled 20 female volleyball players aged 13 ± 1 years old played in two different teams during a regional championship final. Saliva collection was carried out before and after the match. In order to evaluate the neuroendocrine effectors involved in stress and performance, we analyzed cortisol and progesterone levels through Elisa standard kit as well as HSP70 …

NANOGELS AS USEFUL TOOL FOR ALZHEIMER’S DISEASE THERAPY

CONJUGATION STRATEGIES OF INSULIN TO NANOGELS AND BIOLOGICAL ACTIVITY TESTS

High energy radiation processing for the synthesis of insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's Disease

Nanogels are nanoscalar polymeric networks, characterized by a dynamic internal structure and a flexible adaptive shape. When they are used as drug carriers, their flexibility and shape changing ability can facilitate the bypass of biological barriers, ensure protection of the payload and enable interaction of any attached ligand with its receptors. Poly(N-vinyl pyrrolidone)-co-acrylic acid nanogels (NGs) have been produced by ebeam irradiation of diluted aqueous solutions of a water-soluble polymer in the presence of a small amount of acrylic acid. In particular, industrial accelerators and the typical set-ups and doses applied for sterilization have been used. [1, 2] Particle size, molecu…

Neuroprotective effect of a new Insulin-Nanogel system

Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs and contrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a large and flexible surface available for multivalent bioconjugations. NGs can be produced with high yields and through-puts by pulsed electron-beam irradiation of dilute aqueous solutions of water-soluble biocompatible polymers. In this work, a carboxyl functionalized nanogel system (NG), generated by pulsed e-beam irradiation of a semi-dilute poly(N-vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid, with an average diameter in the 60-70…

Mitochondrial Proteomics: An Approach to Identify Cellular Stress Induced By Amyloid-Beta Peptide

Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetic processes. intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase-mediated celi death. Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Mitochondrial functions can be negatively affected by Amyloid Beta-peptide (ABeta), an important component in Alzheimer's disease (AD) pathogenesis, and ABeta can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mito…

Insulin Nanogel as New Strategy for the Treatment of Alzheimer’s Disease

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in neuronal degeneration associated with Alzheimer's disease (AD). Thus, the administration of insulin to the brain could be a strategy for the prevention and treatment of AD disease. With this aim, we have designed, synthesized and characterized a nanogel system (NG) that can be used as substrate for the conjugation of insulin and/or fluorescent molecules relevant for their characterization. In particular, a carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system, has been produced by ionizing radiation starting from th…

Neurobiology of performance anxiety:A new approach

The aim of this study is to investigate the neurobiology of stress/emotionality, creating a multidisciplinary assessment model, which can help to provide psychological and physiological responses depending on the genetic background related to sport performances, social closeness and performance anxiety management in team sports. We enrolled 20 female volleyball players aged 13 ± 1 years old played in two different teams during a regional championship final. Saliva collection was carried out before and after the match. In order to evaluate the neuroendocrine effectors involved in stress and performance, we analyzed cortisol and progesterone levels through Elisa standard kit as well as HSP70 …

A close connection: Alzheimer’s disease and type 2 diabetes

In the recent years a growing body of evidence links insulin resistance and insulin action to neurodegenerative diseases, especially Alzheimer’s disease (AD). The importance of insulin in ageing as well as its role in cognition and other aspects of normal brain functions are well established. The hippocampus and cerebral cortex-distributed insulin and insulin receptor (IR) have been shown to be involved in brain cognitive functions. Conversely, deterioration of IR signaling is involved in agingrelated brain degeneration such as in AD and cognitive impairment in type 2 diabetes patients. Insulin administration, while maintaining euglycemia, improves memory in both healthy adults and Alzheime…

Synthesis and characterization of a new insulin conjugated nanogel for biomedical application

Insulin, a metabolic hormone involved in glucose metabolism, plays also a neuroprotective role in the central nervous system being able to revert the cytotoxic processes induced by Aβ42,a peptide involved in Alzheimer's disease. To reach the brain insulin have to across the BBB therefore an additional delivery strategy results to be necessary. For these aim we performed an insulin conjugated nanogels (NGs-In). Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs and contrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a large and flexible surface available for multivalen…

Sintesi di nanogeli per la veicolazione di insulina al cervello: una strategia per il trattamento della malattia di Alzheimer

I nanogeli sono nanoparticelle polimeriche reticolate idrofile. La struttura polimerica del nanogelo permette la coniugazione di molecole che possano esplicare azioni terapeutiche, diagnostiche e di indirizzamento attivo su siti bersaglio. Le caratteristiche di flessibilità e conformabilità del nanogelo, e delle sue maglie, ne favoriscono l’attraversamento delle barriere biologiche, l’interazione di eventuali ligandi esposti sulla superfice con i recettori target, un’azione protettiva nei confronti del principio attivo incorporato. L’irraggiamento con radiazioni ionizzanti di soluzioni acquose di polimeri è una metodologia sintetica interamente “water-based”, che garantisce rese elevate e c…