Publications by authors named "Sharon Creason"
Macrophages are widely recognized in modulating the foreign body response, and the manner in which they do so largely depends on their activation state, often referred to as their polarization. This preliminary study demonstrates that surface immobilized α-1 acid glycoprotein (AGP), as well as collagen VI (Col6) in conjunction with AGP, can direct macrophages towards the M2 polarization state in vitro and modify the foreign body response in vivo. AGP and Col6 are immobilized onto poly(2-hydroxyethyl methacrylate) (pHEMA) surfaces using carbonyl diimidazole chemistry.
View Article and Find Full Text PDFArticle Synopsis
- Current hemodialysis treatment for end-stage renal disease patients is limited by lengthy sessions and large volumes of dialysate, which hampers the development of portable alternatives.
- Researchers have developed a method to regenerate dialysate using TiO nanowires, demonstrating effective urea removal and minimal production of harmful by-products.
- The study confirms that photodecomposition of urea at therapeutic rates using this technology could facilitate portable dialysis options, improving patient mobility and overall quality of life.
Article Synopsis
- There is a significant demand for improved vascular grafts, especially small diameter non-biologic ones, and existing medium diameter grafts show subpar performance.
- Researchers developed biostable polyurethane scaffolds with 40 μm pores that match the mechanical properties of natural blood vessels, aiming to enhance integration and healing while minimizing foreign body reactions.
- Testing in mice for 3 weeks revealed that these 40 μm porous scaffolds promoted the best angiogenesis and cellular activity, suggesting their potential for use in vascular grafts, tissue engineering, and other medical applications.
Article Synopsis
- * A new surface modification method using zwitterionic carboxybetaine and photosensitive cross-linking polymers is effective in preventing protein adsorption and platelet activation on PVC surfaces.
- * This dip-coating and light illumination technique enhances the hydrophilicity and nonfouling properties of PVC, and it can also be applied to various other medical devices, making it a scalable solution for improving clinical performance.
Development of Methionyl-tRNA Synthetase Inhibitors as Antibiotics for Gram-Positive Bacterial Infections.
Antimicrob Agents Chemother
November 2017
Antibiotic-resistant bacteria are widespread and pose a growing threat to human health. New antibiotics acting by novel mechanisms of action are needed to address this challenge. The bacterial methionyl-tRNA synthetase (MetRS) enzyme is essential for protein synthesis, and the type found in Gram-positive bacteria is substantially different from its counterpart found in the mammalian cytoplasm.
View Article and Find Full Text PDFArticle Synopsis
- To enhance the effectiveness of these inhibitors, researchers investigated a binding fragment that targets a specific region known as the "enlarged methionine pocket" (EMP).
- This led to the discovery of a 6,8-dichloro-tetrahydroquinoline ring, which when substituted into compound 2 resulted in a new compound, 13, showing a remarkable potency with an EC of 4nM.
Article Synopsis
- A screening of a compound library found a promising class of compounds, N-(2-aminoethyl)-N-phenyl benzamides, with potential against Trypanosoma brucei, the parasite causing Human African Trypanosomiasis.
- Researchers synthesized 82 analogues and discovered that compound 73 was particularly effective, showing a low effective concentration (EC) of 0.001μM in vitro tests.
- Compound 73 demonstrated good oral bioavailability and cured 2 out of 3 mice infected with the parasite when administered at a specific dosage, suggesting its potential use as a lead drug for treating the disease.
Article Synopsis
- - The research builds on previous findings of 2-(2-benzamido)ethyl-4-phenylthiazole derivatives that showed potential against Trypanosoma brucei, which causes human African trypanosomiasis, but had poor metabolic stability.
- - This study focuses on synthesizing 65 new analogues through medicinal chemistry optimization, particularly targeting urea derivatives of 2-aryl-benzothiazol-5-amines for improved effectiveness.
- - One promising compound, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole, demonstrated high efficacy, achieving complete cures in mouse models for
Article Synopsis
- - A screening hit against Trypanosoma brucei methionyl-tRNA synthetase was enhanced using a structure-based method, leading to two new series of effective inhibitors: cyclic linker and linear linker series.
- - The compounds from both series showed strong inhibition of T. brucei growth with low toxicity to mammalian cells, particularly compound 16 and 31, which had effective concentrations of 39 nM and 22 nM, respectively.
- - Additionally, compound 31 demonstrated good pharmacokinetic properties after oral doses in mice and moderate brain permeability, making them promising candidates for developing new treatments for human African trypanosomiasis (HAT).
Article Synopsis
- * From 110 analogues created, compound 64, a substituted 2-(3-aminophenyl)imidazopyridine, was found to have strong antiparasitic activity with an EC50 of just 2 nM and displayed favorable druglike characteristics in vitro.
- * This compound was effective when administered orally, curing infected mice at doses as low as 2.5 mg/kg, positioning compound 64 as a potential lead for new treatments against
Article Synopsis
- - Plasmodium falciparum is responsible for around 1 million deaths each year, and growing drug resistance is a significant problem for existing treatments.
- - Researchers have developed potent triazolopyrimidine-based inhibitors that effectively target P. falciparum's dihydroorotate dehydrogenase (PfDHODH), with promising results in mice.
- - A new compound, DSM151, has shown even stronger binding to PfDHODH than previous inhibitors and effectively controls parasites in animal models, marking a significant advancement in potential malaria treatments.
Malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. We previously reported identification of a new class of triazolopyrimidine-based Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. Active compounds from the series contained a triazolopyrimidine ring attached to an aromatic group through a bridging nitrogen atom.
View Article and Find Full Text PDFPlasmodium falciparum causes 1-2 million deaths annually. Yet current drug therapies are compromised by resistance. We previously described potent and selective triazolopyrimidine-based inhibitors of P.
View Article and Find Full Text PDF