A5009424761- Tissue Engineering and Regenerative Medicine
- Prion Diseases and Protein Misfolding
- Wound Healing and Treatments
- Electrospun Nanofibers in Biomedical Applications
- Chemical Synthesis and Analysis
- Trace Elements in Health
- Click Chemistry and Applications
- Surgical Sutures and Adhesives
- Alzheimer's disease research and treatments
- Reconstructive Surgery and Microvascular Techniques
- Bone Tissue Engineering Materials
- Crystallography and molecular interactions
- Neurological diseases and metabolism
- Gastroesophageal reflux and treatments
- Dysphagia Assessment and Management
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Additive Manufacturing and 3D Printing Technologies
- Synthesis of Tetrazole Derivatives
- Quinazolinone synthesis and applications
- Peptidase Inhibition and Analysis
- Biochemical and Structural Characterization
- HIV Research and Treatment
- RNA regulation and disease
- Infectious Diseases and Tuberculosis
University of Oklahoma Health Sciences Center
2024
Laboratoire de Biologie, Bioingéniérie et Bioimagerie ostéoarticulaire
2019-2022
Royal Adelaide Hospital
2015-2019
Hutt Hospital
2013
Christie's
2013
Institute for Neurodegenerative Disorders
2004-2012
University of California, San Francisco
2001-2012
German Center for Neurodegenerative Diseases
2009
La Trobe University
2003
University of Canterbury
1999-2002
Prion diseases in humans and animals are invariably fatal. Prions composed of a disease-causing isoform (PrP(Sc)) the normal host prion protein (PrP(C)) replicate by stimulating conversion PrP(C) into nascent PrP(Sc). We report here that tricyclic derivatives acridine phenothiazine exhibit half-maximal inhibition PrP(Sc) formation at effective concentrations (EC(50)) between 0.3 microM 3 cultured cells chronically infected with prions. The EC(50) for chlorpromazine was microM, whereas...
Prion diseases are characterized by an accumulation of PrP Sc , a misfolded isoform the normal cellular prion protein, C . We previously reported bioactivity acridine-based compounds against replication in scrapie-infected neuroblastoma cells and now report improved potency bis-acridine compounds. Bis-acridines dimeric motif, comprising two acridine heterocycles tethered linker. A library bis-(6-chloro-2-methoxy-acridin-9-yl) bis-(7-chloro-2-methoxy-benzo[ b ][1,5]naphthyridin-10-yl) analogs...
Prion diseases are fatal, untreatable neurodegenerative caused by the accumulation of misfolded, infectious isoform prion protein (PrP), termed PrP(Sc). In an effort to identify novel inhibitors formation, we utilized a high-throughput enzyme-linked immunosorbent assay (ELISA) evaluate PrP(Sc) reduction in prion-infected neuroblastoma cell lines (ScN2a). We screened library approximately 10,000 diverse small molecules 96-well format and identified 121 compounds that reduced levels at...
Abstract Background Two-dimensional data colourings are an effective medium by which to represent three-dimensional in two dimensions. Such "color-grid" representations have found increasing use the biological sciences (e.g. microarray 'heat maps' and bioactivity data) as they particularly suited complex sets offer alternative graphical included traditional statistical software packages. The effectiveness of color-grids lies their design, introduces a standard for customizable...
2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit replication in cultured cells. Here, we report findings from a comprehensive structure−activity relationship study the 6-aminopyridine-3,5-dicarbonitrile scaffold. We identify with significantly improved bioactivity (approximately 40-fold) against infectious isoform (PrPSc) suitable pharmacokinetic profiles to warrant evaluation animal models disease.
The phenotypic effect of prions on host cells is influenced by the physical properties prion strain and its level accumulation. In mammalian cell cultures, accumulation determined interplay between de novo formation, catabolism, division, horizontal cell-to-cell transmission. Understanding this dynamic enables analytical modeling protein-based heritability infectivity. Here, we quantitatively measured these competing effects in a subline neuroblastoma (N2a) propose concordant reaction...
Proteases play a critical role in the ordered remodelling of extracellular matrix (ECM) components during wound healing and tissue regeneration. However, usually proteolysis is compromised chronic wounds due to over-expression high concentrations metalloproteinase's (MMPs) neutrophil elastase (NE). Ovine forestomach (OFM) decellularised matrix-based biomaterial developed for regeneration applications, including treatment wounds, heterogeneous mixture ECM proteins proteoglycans that retains...
Abstract Purpose Two innovative reinforced biologic materials were studied in a non-human primate hernia repair model. The test articles, which combine layers of ovine decellularized extracellular matrix with minimal amounts synthetic polymer, evaluated for their performance as measured by inflammatory response, healing kinetics, integration, and remodeling into functional host tissue. For comparison, seven clinically used meshes also studied. Methods Animals implanted articles surgically...
The suitability of the ovine forestomach matrix (OFM) for treatment recalcitrant wounds was evaluated in 19 patients. At 12 weeks, 50% had closed, and average reduction surface area 73.4%. Promising outcomes this initial series support clinical consideration OFM.
The aims of this study were to evaluate the microbiological trends in severe odontogenic infections requiring hospital admission South Australian Oral and Maxillofacial Surgery Unit. Rates antibiotic resistance empirical regimens determined quantify clinical implications antibiotic-resistant infections.A retrospective case audit was performed on all admitted Royal Adelaide Hospital over a 9-year period. Data collected regarding demographics, culture sensitivity results, outcome variables.Of...
Ovine forestomach matrix (OFM) is a decellularized extracellular (dECM) biomaterial that serves as scaffold for remodeling damaged soft tissue. dECM biomaterials are used in variety of clinical applications, and their regenerative capacity encoded not only biophysical properties but also molecular diversity. In this study, the proteome OFM was characterized via both targeted global mass spectrometry (MS) with use heavy isotope labeled (SIL) internal standards. Proteins were identified...
Decellularized extracellular matrix (dECM)–based biomaterials are of great clinical utility in soft tissue repair applications due to their regenerative properties. Multi-layered dECM devices have been developed for indications where additional thickness and biomechanical performance required. However, traditional approaches the fabrication multi-layered introduce laminating materials or chemical modifications that may impair biological functionality material. Using an established...
ABSTRACT Venous leg ulcers (VLUs) are traditionally managed with standard‐of‐care dressings, compression and appropriate adjunctive venous interventions for pathologic reflux. Due to pathophysiological complexity underlying patient comorbidities, conducting randomised controlled trials evaluate the comparative efficacy of advanced treatment modalities is difficult, as many patients would likely be excluded. This retrospective, pragmatic, real‐world evidence (RWE) study compared healing...
Quinacrine (QA), an antimalarial drug used for over seven decades, has been found to have potent antiprion activity in vitro. To determine whether QA can be treat prion diseases, we investigated its metabolism and ability traverse the blood-brain barrier mice. In vitro vivo, identified by liquid chromatography-tandem mass spectrometry major metabolic pathway of as <i>N</i>-desethylation compared our results with authentic reference compound. The human cytochrome (P450) isoforms involved...
Abstract Ovine forestomach matrix (OFM) is a native and functional decellularized extracellular biomaterial that supports cell adhesion proliferation remodeled during the course of tissue regeneration. Small angle X‐ray scattering demonstrated OFM retains collagen architecture ( d spacing = 63.5 ± 0.2 nm, orientation index 20°). The biophysical properties were further defined using ball‐burst, uniaxial suture retention testing, as well quantification aqueous permeability. was relatively...
The main cytotoxic component in New Zealand collections of the liverwort Trichocolea mollissima was identified as methyl 4-[(5-oxogeranyl)oxy]-3-methoxybenzoate, a structure that has not been reported previously. Two double-bond isomers this geranyl ether were present at lower levels. Reinvestigation benzoates from Japanese tomentella led to identification four ethers (including two three compounds T. mollissima), which had previously assigned incorrect ester structures. One compound,...
The lipophilic cationic compound quinacrine has been used as an antimalarial drug for over 75 years but its pharmacokinetic profile is limited. Here, we report on the properties of in mice. Following oral dose 40 mg/kg/day 30 days, concentration brain wild-type mice was maintained at a ∼1 µM. As substrate P-glycoprotein (P-gp) efflux transporter, actively exported from brain, preventing accumulation to levels that may show efficacy some disease models. In brains P-gp–deficient Mdr10/0 mice,...
Chronic lower-extremity defects may lead to major amputations and have severe consequences on patient quality of life mortality. Dermal matrices become part the reconstructive ladder are often deployed in these scenarios quickly build neodermis, especially volumetric over exposed bone tendon initially, allow for subsequent closure by means split-thickness skin grafting (STSG) or secondary intention. Ovine forestomach matrix (OFM) is a decellularized extracellular (ECM) bioscaffold available...
Parasitic diseases are of enormous public health significance in developing countries-a situation compounded by the toxicity and resistance to many current chemotherapeutics. We investigated a focused library 18 structurally diverse bis-acridine compounds for vitro bioactivity against seven protozoan one helminth parasite species compared bioactivities cytotoxicities these toward various mammalian cell lines. Structure-activity relationships demonstrated influence both linker structure...