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- Fu, Le, et al.
(author)
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Preparation of High Percentage α-Calcium SulfateHemihydrate via a Hydrothermal Method
- 2017
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In: Journal of Biomaterials and Nanobiotechnology. - : Scientific Research Publishing, Inc.. - 2158-7027 .- 2158-7043. ; 8, s. 36-49
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Journal article (peer-reviewed)abstract
- α-calciumα-calcium sulfate hemihydrate ( -HH) is known to be suitable for application as bone void filler. High percentage ofα( -HH) is known to be suitable for application as bone void filler. High percentage ofα α -HHbone void filler. High percentage ofα -HH is obviously needed for medical applica-tions, especially for implantation. Three commercially available calcium sulfate di-·2H2O) with different sizes and surface morphologies were usedhydrates (DH, CaSO4·2H2CaSO4·2H2O)α-HH via a hydrothermal method.as starting materials to synthesize high percentageα-HHThe median particle sizes of the three types of DH were 946.7 µm, 162.4 µm and 62.4µm, respectively. They were named as DH-L, DH-M and DH-S in this paper. Theparticle size distribution, morphology and phase composition of the raw materialswere evaluated before synthesis. SEM results revealed that DH-L consisted of irregu-lar large particles, while DH-M and DH-S were composed of plate-like particles withsome small ones. High percentage HH can be obtained with proper synthesis para-meters by hydrothermal method, specifically, 105˚C/90 min for DH-L (achieving98.8% HH), 105˚C/30 min for DH-M (achieving 96.7% HH) and 100˚C/45 min forDH-S (achieving 98.4% HH). All the synthesized HH were hexagonal columns, de-α -phase HH. The particle size and morphology of start-α -phasemonstrating that they wereing material (DH) have significant influences on not only the rate of phase transitionα -HH.α -HH. Calcium sulfate dihydrate cementsbut also the morphology of the synthesizedα -HH. The highest compressive strength of cal-α -HH.were prepared by the synthesizedcium sulfate dihydrate cement was 17.2 MPa. The results show that the preparationα -HHα -HH is feasible via a hydrothermal method and the process canof high percentagebe further scaled up to industrial scale production.
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- Nordström, Eva, et al.
(author)
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ABBV-0805, a novel antibody selective for soluble aggregated alpha-synuclein, prolongs lifespan and prevents buildup of alpha-synuclein pathology in mouse models of Parkinson's disease
- 2021
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In: Neurobiology of Disease. - : Elsevier. - 0969-9961 .- 1095-953X. ; 161
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Journal article (peer-reviewed)abstract
- A growing body of evidence suggests that aggregated alpha-synuclein, the major constituent of Lewy bodies, plays a key role in the pathogenesis of Parkinson's disease and related alpha-synucleinopathies. Immunotherapies, both active and passive, against alpha-synuclein have been developed and are promising novel treatment strategies for such disorders. Here, we report on the humanization and pharmacological characteristics of ABBV-0805, a monoclonal antibody that exhibits a high selectivity for human aggregated alpha-synuclein and very low affinity for monomers. ABBV-0805 binds to a broad spectrum of soluble aggregated alpha-synuclein, including small and large aggregates of different conformations. Binding of ABBV-0805 to pathological alpha-synuclein was demonstrated in Lewy body-positive post mortem brains of Parkinson's disease patients. The functional potency of ABBV-0805 was demonstrated in several cellular assays, including Fc gamma-receptor mediated uptake of soluble aggregated alpha-synuclein in microglia and inhibition of neurotoxicity in primary neurons. In vivo, the murine version of ABBV-0805 (mAb47) displayed significant dose dependent decrease of alpha-synuclein aggregates in brain in several mouse models, both in prophylactic and therapeutic settings. In addition, mAb47 treatment of alpha-synuclein transgenic mice resulted in a significantly prolonged survival. ABBV-0805 selectively targets soluble toxic alpha-synuclein aggregates with a picomolar affinity and demonstrates excellent in vivo efficacy. Based on the strong preclinical findings described herein, ABBV-0805 has been progressed into clinical development as a potential disease-modifying treatment for Parkinson's disease.
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