Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity.     

The HIV‐1 gp41 ectodomain is cleaved by matriptase to produce a chemotactic peptide that acts through FPR2

Several aspects of HIV‐1 virulence and pathogenesis are mediated by the envelope protein gp41. Additionally, peptides derived from the gp41 ectodomain have been shown to induce chemotaxis in monocytes and neutrophils. Whereas this chemotactic activity has been reported, it is not known how these peptides could be produced under biological conditions. The heptad repeat 1 (HR1) region of gp41 is exposed to the extracellular environment and could therefore be susceptible to proteolytic processing into smaller peptides. Matriptase is a serine protease expressed at the surface of most epithelia, including the prostate and mucosal surfaces. Here, we present evidence that matriptase efficiently cleaves the HR1 portion of gp41 into a 22‐residue chemotactic peptide MAT‐1, the sequence of which is highly conserved across HIV‐1 clades. We found that MAT‐1 induced migration of primary neutrophils and monocytes, the latter of which act as a cellular reservoir of HIV during early stage infection. We then used formyl peptide receptor 1 (FPR1) and FPR2 inhibitors, along with HEK 293 cells, to demonstrate that MAT‐1 can induce chemotaxis specifically using FPR2, a receptor found on the surface of monocytes, macrophages and neutrophils. These findings are the first to identify a proteolytic cleavage product of gp41 with chemotactic activity and highlight a potential role for matriptase in HIV‐1 transmission and infection at epithelial surfaces and within tissue reservoirs of HIV‐1.     

Sensitive colorimetric detection of ochratoxin A by a dual-functional Au/Fe3O4 nanohybrid-based aptasensor

A novel colorimetric aptasensor based on a Au/Fe₃O₄ nanohybrid was developed to detect ochratoxin A (OTA). The aptasensor is composed of a free OTA aptamer, a Au/Fe₃O₄ nanohybrid coated with biotinylated complementary DNA of the OTA aptamer (biotin-cDNA-Au/Fe₃O₄), and free alkaline-phosphatase-labeled streptavidin (SA-ALP). The Au/Fe₃O₄ nanohybrid not only immobilizes biotin-cDNA but also magnetically separates SA-ALP from the sample solution. One part of the OTA aptamer sequence hybridizes with biotin-cDNA immobilized on Au/Fe₃O₄, and the left part of the OTA aptamer sequence covers the biotin and blocks the specific interaction between biotin and SA-ALP. OTA can interrupt the interaction of OTA aptamer binding to biotin-cDNA-Au/Fe₃O₄ and can inhibit the shielding effect of the OTA aptamer on biotin. The amount of SA-ALP that can be captured by biotin-cDNA-Au/Fe₃O₄ thus increases with increasing OTA concentration. Through a simple magnetic separation, the collected SA-ALP-linked Au/Fe₃O₄ can produce a yellow-colored solution in the presence of p-nitrophenyl phosphate (p-NPP). This colorimetric aptasensor can detect OTA as low as 1.15 ng mL⁻¹ with high specificity.

A novel colorimetric aptasensor based on a Au/Fe₃O₄ nanohybrid was developed to detect ochratoxin A (OTA).     

Cribriform Morular Variant of Papillary Thyroid Carcinoma in a Patient with an Incidental Neck Lump: a Case Report and Review of the Literature

The cribriform morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare morphologic entity that is associated with familial adenomatous polyposis (FAP). We report a case of a young lady with an incidentally discovered right-sided neck nodule on ultrasonography with a diagnosis of CMV-PTC confirmed on thyroidectomy and review the literature associated with the clinical presentation, imaging characteristics, pathological findings and the association with FAP.     

Site-specific functionalization with amino,guanidinium, and imidazolyl groups enabling the activation of 10–23 DNAzyme

10–23 DNAzyme has been extensively explored as a therapeutic and biotechnological tool, as well as in DNA computing. Faster cleavage or transformation is always needed. The present research displays a rational modification approach for a more efficient DNAzyme. In the catalytic core, amino, guanidinium and imidazolyl groups were introduced for its chemical activation through the adenine base. Among the six adenine residues, A9 is the unique residue that realizes all the positive effects; the 6-amino and 8-position of adenine and the 7-position of 8-aza-7-deaza-adenine could be used for the introduction of the functional groups. A12 is a new choice for catalytic improvement with an 8-substituent. Therefore, more active DNAzymes could be expected by this nucleobase-modified activation approach.

Chemical activation of 10–23 DNAzyme was realized at A9 modified with active functional groups amino, guanidinium, and imidazolyl groups.