Enzyme–free uric acid electrochemical sensors using β–cyclodextrin modified carboxylic acid functionalized carbon nanotubes

Carboxylic acid-functionalized multi-walled carbon nanotubes (COOH-MWCNT) were modified via ultrasonication with β-cyclodextrin (β-CD) to obtain a COOH-MWCNT:β-CD nanocomposite material for the purpose of developing an enzyme-free electrochemical sensor for uric acid—a clinically relevant molecule implemented in pregnancy-induced hypertension diagnosis. The nanocomposite material is deposited onto glassy carbon electrodes and subsequently capped with layers of Nafion and Hydrothane polyurethane. The surface morphology and electronic structure of the nanocomposite material were characterized using UV–Vis, TEM, and FTIR. The performance of the electrochemical sensor was measured through direct injection of UA during amperometry. With the high surface area of the COOH-MWCNT in concert with the selectivity provided by β-CD, the composite system outperforms similar COOH-MWCNT systems, displaying enhanced UA sensitivity versus films with only COOH-MWCNT. With the improved sensitivity (4.28 ± 0.11 µA mM−1) and fast response time (4.0 ± 0.5 s), the sensors offer wide detection of UA across clinically relevant ranges (100–700 μM) as well as demonstrated selectivity against various interferents

Investing in antibiotics to alleviate future catastrophic outcomes : what is the value of having an effective antibiotic to mitigate pandemic influenza?

Over 95% of post-mortem samples from the 1918 pandemic, which caused 50 to 100 million deaths, showed bacterial infection complications. The introduction of antibiotics in the 1940s has since reduced the risk of bacterial infections, but growing resistance to antibiotics could increase the toll from future influenza pandemics if secondary bacterial infections are as serious as in 1918, or even if they are less severe. We develop a valuation model of the option to withhold wide use of an antibiotic until significant outbreaks such as pandemic influenza or foodborne diseases are identified. Using real options theory, we derive conditions under which withholding wide use is beneficial, and calculate the option value for influenza pandemic scenarios that lead to secondary infections with a resistant Staphylococcus aureus strain. We find that the value of withholding an effective novel oral antibiotic can be positive and significant unless the pandemic is mild and causes few secondary infections with the resistant strain or if most patients can be treated intravenously. Although the option value is sensitive to parameter uncertainty, our results suggest that further analysis on a case-by-case basis could guide investment in novel agents as well as strategies on how to use them

Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells

Tumor escape is linked to multiple mechanisms, notably the liberation, by tumor cells, of soluble factors that inhibit the function of dendritic cells (DC). We have shown that melanoma gangliosides impair DC differentiation and induce their apoptosis. The present study was aimed to give insight into the mechanisms involved. DC apoptosis was independent of the catabolism of gangliosides since lactosylceramide did not induce cell death. Apoptosis induced by GM3 and GD3 gangliosides was not blocked by inhibitors of de novo ceramide biosynthesis, whereas the acid sphingomyelinase inhibitor desipramine only prevented apoptosis induced by GM3. Furthermore, our results suggest that DC apoptosis was triggered via caspase activation, and it was ROS dependent with GD3 ganglioside, suggesting that GM3 and GD3 induced apoptosis through different mechanisms

Discovery of Dual-Action Membrane-Anchored Modulators of Incretin Receptors

The glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP-1) receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ligand (MTL) technology, the present study focused on defining optimized modulators of these receptors, as well as exploring how local anchoring influences soluble peptide function.Serial substitution of residue 7 in membrane-tethered GIP (tGIP) led to a wide range of activities at the GIP receptor, with [G(7)]tGIP showing enhanced efficacy compared to the wild type construct. In contrast, introduction of G(7) into the related ligands, tGLP-1 and tethered exendin-4 (tEXE4), did not affect signaling at the cognate GLP-1 receptor. Both soluble and tethered GIP and GLP-1 were selective activators of their respective receptors. Although soluble EXE4 is highly selective for the GLP-1 receptor, unexpectedly, tethered EXE4 was found to be a potent activator of both the GLP-1 and GIP receptors. Diverging from the pharmacological properties of soluble and tethered GIP, the newly identified GIP-R agonists, (i.e. [G(7)]tGIP and tEXE4) failed to trigger cognate receptor endocytosis. In an attempt to recapitulate the dual agonism observed with tEXE4, we conjugated soluble EXE4 to a lipid moiety. Not only did this soluble peptide activate both the GLP-1 and GIP receptors but, when added to receptor expressing cells, the activity persists despite serial washes.These findings suggest that conversion of a recombinant MTL to a soluble membrane anchored equivalent offers a means to prolong ligand function, as well as to design agonists that can simultaneously act on more than one therapeutic target

Severe Community-acquired Pneumonia Due to Staphylococcus aureus, 2003–04 Influenza Season

S. aureus community-acquired pneumonia has been reported from 9 states

Segregation of Fluorescent Membrane Lipids into Distinct Micrometric Domains: Evidence for Phase Compartmentation of Natural Lipids?

Background: We recently reported that sphingomyelin (SM) analogs substituted on the alkyl chain by various fluorophores (e.g. BODIPY) readily inserted at trace levels into the plasma membrane of living erythrocytes or CHO cells and spontaneously concentrated into micrometric domains. Despite sharing the same fluorescent ceramide backbone, BODIPY-SM domains segregated from similar domains labelled by BODIPY-D-e-lactosylceramide (D-e-LacCer) and depended on endogenous SM. Methodology/Principal Findings. We show here that BODIPY-SM further differed from BODIPY-D-e-LacCer or -glucosylceramide (GlcCer) domains in temperature dependence, propensity to excimer formation, association with a glycosylphosphatidylinositol (GPI)-anchored fluorescent protein reporter, and lateral diffusion by FRAP, thus demonstrating different lipid phases and boundaries. Whereas BODIPY-D-e-LacCer behaved like BODIPY-GlcCer, its artificial stereoisomer, BODIPY-L-t-LacCer, behaved like BODIPY- and NBD-phosphatidylcholine (PC). Surprisingly, these two PC analogs also formed micrometric patches yet preferably at low temperature, did not show excimer, never associated with the GPI reporter and showed major restriction to lateral diffusion when photobleached in large fields. This functional comparison supported a three-phase micrometric compartmentation, of decreasing order: BODIPY-GSLs > -SM > -PC (or artificial L-t-LacCer). Co-existence of three segregated compartments was further supported by double labelling experiments and was confirmed by additive occupancy, up to ~70% cell surface coverage. Specific alterations of BODIPY-analogs domains by manipulation of corresponding endogenous sphingolipids suggested that distinct fluorescent lipid partition might reflect differential intrinsic propensity of endogenous membrane lipids to form large assemblies. Conclusions/Significance. We conclude that fluorescent membrane lipids spontaneously concentrate into distinct micrometric assemblies. We hypothesize that these might reflect preexisting compartmentation of endogenous PM lipids into non-overlapping domains of differential order: GSLs > SM > PC, resulting into differential self-adhesion of the two former, with exclusion of the latter

Comparison of the virulence of exopolysaccharide-producing Prevotella intermedia to exopolysaccharide non-producing periodontopathic organisms

<p>Abstract</p> <p>Background</p> <p>Evidence in the literature suggests that exopolysaccharides (EPS) produced by bacterial cells are essential for the expression of virulence in these organisms. Secreted EPSs form the framework in which microbial biofilms are built.</p> <p>Methods</p> <p>This study evaluates the role of EPS in <it>Prevotella intermedia </it>for the expression of virulence. This evaluation was accomplished by comparing EPS-producing <it>P. intermedia </it>strains 17 and OD1-16 with non-producing <it>P. intermedia </it>ATCC 25611 and <it>Porphyromonas gingivalis </it>strains ATCC 33277, 381 and W83 for their ability to induce abscess formation in mice and evade phagocytosis.</p> <p>Results</p> <p>EPS-producing <it>P. intermedia </it>strains 17 and OD1-16 induced highly noticeable abscess lesions in mice at 10⁷colony-forming units (CFU). In comparison, <it>P. intermedia </it>ATCC 25611 and <it>P. gingivalis </it>ATCC 33277, 381 and W83, which all lacked the ability to produce viscous materials, required 100-fold more bacteria (10⁹CFU) in order to induce detectable abscess lesions in mice. Regarding antiphagocytic activity, <it>P. intermedia </it>strains 17 and OD1-16 were rarely internalized by human polymorphonuclear leukocytes, but other strains were readily engulfed and detected in the phagosomes of these phagocytes.</p> <p>Conclusions</p> <p>These results demonstrate that the production of EPS by <it>P. intermedia </it>strains 17 and OD1-16 could contribute to the pathogenicity of this organism by conferring their ability to evade the host's innate defence response.</p