Saint Louis University

About: Saint Louis University is a education organization based out in St Louis, Missouri, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 18927 authors who have published 34895 publications receiving 1267475 citations. The organization is also known as: SLU & St. Louis University.

3D printed microfluidic devices with integrated versatile and reusable electrodes

Abstract: We report two 3D printed devices that can be used for electrochemical detection In both cases, the electrode is housed in commercially available, polymer-based fittings so that the various electrode materials (platinum, platinum black, carbon, gold, silver) can be easily added to a threaded receiving port printed on the device; this enables a module-like approach to the experimental design, where the electrodes are removable and can be easily repolished for reuse after exposure to biological samples The first printed device represents a microfluidic platform with a 500 × 500 μm channel and a threaded receiving port to allow integration of either polyetheretherketone (PEEK) nut-encased glassy carbon or platinum black (Pt-black) electrodes for dopamine and nitric oxide (NO) detection, respectively The embedded 1 mm glassy carbon electrode had a limit of detection (LOD) of 500 nM for dopamine and a linear response (R2 = 099) for concentrations between 25–500 μM When the glassy carbon electrode was coated with 005% Nafion, significant exclusion of nitrite was observed when compared to signal obtained from equimolar injections of dopamine When using flow injection analysis with a Pt/Pt-black electrode and standards derived from NO gas, a linear correlation (R2 = 099) over a wide range of concentrations (76–190 μM) was obtained, with the LOD for NO being 1 μM The second application showcases a 3D printed fluidic device that allows collection of the biologically relevant analyte adenosine triphosphate (ATP) while simultaneously measuring the release stimulus (reduced oxygen concentration) The hypoxic sample (48 ± 05 ppm oxygen) released 24 ± 04 times more ATP than the normoxic sample (84 ± 06 ppm oxygen) Importantly, the results reported here verify the reproducible and transferable nature of using 3D printing as a fabrication technique, as devices and electrodes were moved between labs multiple times during completion of the study

Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2

Abstract: Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer and other human diseases. Fumagillin and ovalicin compose a class of structurally related natural products that potently inhibit angiogenesis by blocking endothelial cell proliferation. A synthetic analog of fumagillin, TNP-470, is currently undergoing clinical trials for treatment of a variety of cancers. A common target for fumagillin and ovalicin recently was identified as the type 2 methionine aminopeptidase (MetAP2). These natural products bind MetAP2 covalently, inhibiting its enzymatic activity. The specificity of this binding is underscored by the lack of inhibition of the closely related type 1 enzyme, MetAP1. The molecular basis of the high affinity and specificity of these inhibitors for MetAP2 has remained undiscovered. To determine the structural elements of these inhibitors and MetAP2 that are involved in this interaction, we synthesized fumagillin analogs in which each of the potentially reactive epoxide groups was removed either individually or in combination. We found that the ring epoxide in fumagillin is involved in the covalent modification of MetAP2, whereas the side chain epoxide group is dispensable. By using a fumagillin analog tagged with fluorescein, His-231 in MetAP2 was identified as the residue that is covalently modified by fumagillin. Site-directed mutagenesis of His-231 demonstrated its importance for the catalytic activity of MetAP2 and confirmed that the same residue is covalently modified by fumagillin. These results, in agreement with a recent structural study, suggest that fumagillin and ovalicin inhibit MetAP2 by irreversible blockage of the active site.

Safety and efficacy of sofosbuvir‐containing regimens in hepatitis C‐infected patients with impaired renal function

Abstract: Background & Aims Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR). Methods HCV-TARGET database is a multicentre, longitudinal ‘real-world’ treatment cohort. Results A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4–6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m2. Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400–1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82–83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31–45 had similar frequencies of efficacy and safety outcomes. Conclusions Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m2) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.