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Chitosan Microspheres And Films Used In Controlled ReleaseUylukcuoglu, Beyza 01 September 2003 (has links) (PDF)
Thalassemia, a genetic blood disorder, occurs as a result of deformations of hemoglobin structures. Patients with thalassemia develop iron overload from chronic blood transfusions and require regular iron chelation to prevent potentially fatal iron-related complications. Deferiprone is a commercially available drug used as iron chelator for the treatment of thalassemia but the very long-term effectiveness is not clearly known yet. Therefore, some studies were carried out to find effective alternative drugs or delivery methods for treatment of thalassemia. Controlled delivery, which offers safer, more convenient, and more effective means of administering actives, seems promising with this respect. Chitosan, a natural biopolymer produced from deacetylation of chitin, has a variety of promising pharmaceutical uses and is presently considered as a novel carrier material in drug delivery systems.
In this study, chitosan microspheres having different degree of deacetylation (DDA) and containing Deferiprone were prepared by oil/water emulsion method and by crosslinking with gluteraldehyde. Particle size, SEM, and in vitro drug release analysis were performed. The average sizes of the prepared microspheres increased with increasing degree of deacetylation of chitosan and with decreasing crosslinking degree. In vitro drug release studies showed that, the release rate of Deferiprone increased as the crosslinking degree increased, contrary to the expectations. This is explained by the crystalline structure of lightly crosslinked chitosan which have ordered and dense structure causing slower release rate for Deferiprone compare to highly crosslinked structures.
In the second stage of the study, chitosan films hardened with gluteraldehyde were prepared by film casting method. IR, DSC and mechanical analysis were performed. For the films with various crosslinking degrees, it was found that UTS values differed from 50.6 MPa to 102.7 MPa, mean elastic modulus values differed from 3328.7 MPa to 3790.1 MPa and SAB values differed from 2.06% to 4.29%.
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Ironing out the pathophysiology of neurodegeneration with brain iron accumulation (NBIA) : clinical investigations and disease modelling yield novel evidence of systemic dysfunction and provide a robust and accurate disease model of NBIAMinkley, Michael 01 May 2018 (has links)
Neurodegeneration with Brain Iron Accumulation (NBIA) disorders, such as Phospholipase A2G6-Associated Neurodegeneration (PLAN) and Pantothenate Kinase-Associated Neurodegeneration (PKAN), are a group of rare early-onset, genetic disorders characterized by neurodegeneration and iron accumulation inside of the basal ganglia (BG), which is accompanied by progressive motor symptoms. In order to address the limitations in available models of NBIA, a B6.C3-Pla2g6m1J/CxRwb mouse model of PLAN was characterized. This model demonstrated key hallmarks of the disease presentation in NBIA, including a severe and early-onset motor deficit, neurodegeneration inside of the substantia nigra (SN) including a loss of dopaminergic function and the formation of abnormal spheroid inclusions as well as iron accumulation. The capture of these hallmarks of NBIA makes this an ideal animal research model for NBIA.
Additionally, exploration of candidate systemic biomarkers of NBIA was performed in a case study of a patient with PLAN and in a cohort of 30 patients with PKAN. These investigations demonstrated reductions in transfer and slight, but not significant elevations in soluble transferrin receptor. No significant difference was seen in serum iron parameters. A systemic disease burden including chronic oxidative stress; elevated malondialdehyde, and inflammation; elevated C-reactive protein (CRP), IL-6 and TNFα was noted in both investigations. A number of candidate protein biomarkers including: fibrinogen, transthyretin, zinc alpha-2 glycoprotein and retinol binding protein were also identified. These markers correlated with measures of the severity of iron loading in the globus pallidus (GP); based on R2* magnetic resonance imaging (MRI) and the severity of motor symptoms (Barry-Albright Dystonia Rating Scale) making them potential candidates markers of dysfunction in NBIA. In the patient with PLAN, 37 weeks of therapy with the iron chelator deferiprone (DFP) as well as 20 months of therapy with the antioxidants alpha lipoic acid (ALA) and n-acetylcysteine (NAC) were efficacious in reducing the systemic oxidative and inflammatory disease burden, but it did not significantly alter the progression of the disease. In the antioxidant therapy, this efficacy was primarily due to ALA. When the cohort of patients with PKAN were treated with DFP for 18 months it was highly efficacious in lowering brain iron accumulation in the GP. No significant reduction in the speed of disease progression was seen in DFP treated patients compared to placebo based on initial analysis. Similar to the PLAN patient, DFP also mitigated the systemic disease burden in PKAN patients. In both cases DFP was well tolerated and had minimal impact on serum iron levels, TIBC and transferrin saturation. Collectively these investigations provide valuable insights into disease progression in NBIA. They also provide tools to aid further investigations in NBIA. These are provided in the form of a well-characterized B6.C3-Pla2g6m1J/CxRwb model of PLAN, which robustly captures the disease presentation seen in patients, as well as a panel of systemic blood-based markers of disease burden in NBIA and candidate markers of dysfunction in NBIA. These markers were used to assess two novel therapies in NBIA chelation with DFP and antioxidant therapy with ALA and NAC. / Graduate / 2019-04-19
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Alpha-synuclein aggregation: visualization by X-ray techniques and its modulation by ironCarboni, Eleonora 19 October 2016 (has links)
No description available.
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