Determination of erythrocyte deformability and its correlation to cellular ATP release using microbore tubing with diameters that approximate resistance vessels in vivo

A novel method is described for measuring the deformability of red blood cells (RBCs) in tubing whose diameters approximate forces encountered in vivo. Here, RBCs from rabbits are loaded into a 50 cm section of 75 microm id microbore tubing and connected to a syringe pump. This section of tubing is then connected to a 15 cm section of 25 microm id tubing. As buffer is pumped through the flow system, the RBCs are evacuated from both sections of tubing. However, the inability of the RBCs to move freely through the 25 mirom id section of tubing results in a buildup of cells at the inlet of this portion of tubing. The continued force output by the syringe pump results in a deformation of the RBCs until all of the cells are eventually evacuated from the flow system. It was found that a measurement of the time required to reach half of the maximum pressure (1/2 P(max)) may be used as an indicator of the RBC deformability. For a given sample, a simple buffer results in less time to reach 1/2 P(max) (6.9 +/- 0.2 s) than deformable RBCs (21.6 +/- 0.8 s). To verify that the increased amount of time to reach 1/2 P(max) is indeed due to the RBCs, various hematocrits of an RBC sample were investigated and, as expected, it was found that a 12% RBC hematocrit had a higher 1/2 P(max) value (26.0 s +/- 2.2 s) when compared to a 7% hematocrit (19.1 +/- 0.3 s). In addition, RBCs chemically stiffened with glutaraldehyde were shown to be 25% less deformable than normal RBCs. Finally, a study was performed to examine the relationship between RBC deformability and ATP release and it was found that ATP release increased as a function of RBC deformability. This method greatly simplifies deformability measurements, employing only a syringe pump and microbore tubing, and may lead to a more complete understanding of the physiological significance of erythrocyte deformability.     

Synergistic effect between TiO2 sol–gel and Degussa P25 in dye photodegradation

The TiO₂ powders were synthesized by versatile and low cost sol–gel process using HNO₃ and titanium tetra-isopropoxide (volumetric ratio of 4:1) following by the hydrolysis reaction. The powders show the two polymorphs of TiO₂: 96 % anatase and 4 % brookite, due to acidic condition (pH = 3). Thin films of titanium oxide were obtained by dip-coating, using the sol–gel of titanium oxide mixed with commercial Degussa P25 into a weight ratio 1:1 or 1:1.5, to enhance the synergistic effect of anatase/rutile ratio aiming at increasing the efficiency of the TiO₂ photocatalyst in dyes degradation. The thin film surface (charge and morphology) was controlled by polymer (poly-ethylene glycol) and surfactant (Sodium dodecyl sulphate, Triton X100) addition. The titanium oxide was characterized by particle size analyzer, contact angle measurements, X-ray diffraction, scanning electron microscopy, and atomic force microscopy. The photocatalytic properties of powders and coatings were evaluated based on the degradation efficiency of two reference dyes (methyl orange and methylene blue). The results outline that poly(ethylene glycol) and films morphologies are the most influential factors that affecting the photocatalytic activity.     

Investigation of thermal stability, spectral, magnetic, and antimicrobial behavior for new complexes of Ni(II), Cu(II), and Zn(II) with a bismacrocyclic ligand

Novel complexes of type M₂LCl₄·nH₂O (M: Ni, n = 4; M: Cu, n = 2.5 and M: Zn, n = 1.5; L: ligand resulted from 1,3-phenylenediamine, 3,6-diazaoctane-1,8-diamine, and formaldehyde one-pot condensation) were synthesized and characterized. The ligand was also isolated and characterized. The complexes features have been assigned from microanalytical, electrospray ionization tandem mass spectrometry, IR, UV–vis, ¹H NMR, and EPR spectra as well as magnetic data at room temperature. Simultaneous thermogravimetric/dynamic scanning calorimetry/evolved gas analysis measurements were performed to evidence the nature of the gaseous products formed in each step. Processes as water elimination, fragmentation, and oxidative degradation of the organic ligand as well as chloride elimination were observed during the thermal decomposition. The final product of decomposition was metal(II) oxide except for copper complex where CuCl remained also in the oxide network. The complexes exhibited an improved antibacterial activity in comparison with the ligand concerning both planktonic as well as biofilm-embedded cells.     

Using hydrogen bonds to direct the assembly of crowded aromatics

This Minireview details the design, synthesis, and self-assembly of a new class of crowded aromatics that form columnar superstructures. The assembly of these subunits produces helical and polar stacks, whose assembly can be directed with electric fields. In concentrated solutions, these self-assembled helical rods exhibit superhelical arrangements that reflect circularly polarized light at visible wavelengths. Depending on the side chains employed, spin-cast films yield either polar monolayers or isolated strands of molecules that can be visualized with scanning probe microscopy. Also detailed herein are methods to link these mesogens together to produce monodisperse oligomers that fold into defined secondary conformations.     

Design and synthesis of a bivalent ligand to explore the putative heterodimerization of the mu opioid receptor and the chemokine receptor CCR5

The bivalent ligand approach has been utilized not only to study the underlying mechanism of G protein-coupled receptors dimerization and/or oligomerization, but also to enhance ligand affinity and/or selectivity for potential treatment of a variety of diseases by targeting this process. Substance abuse and addiction have made both the prevention and the treatment of human immunodeficiency virus (HIV) infection more difficult to tackle. Morphine, a mu opioid receptor (MOR) agonist, can accelerate HIV infection through up-regulating the expression of the chemokine receptor CCR5, a well-known co-receptor for HIV invasion to the host cells and this has been extensively studied. Meanwhile, two research groups have described the putative MOR-CCR5 heterodimers in their independent studies. The purpose of this paper is to report the design and synthesis of a bivalent ligand to explore the biological and pharmacological process of the putative MOR-CCR5 dimerization phenomenon. The developed bivalent ligand thus contains two distinct pharmacophores linked through a spacer; ideally one of which will interact with the MOR and the other with the CCR5. Naltrexone and Maraviroc were selected as the pharmacophores to generate such a bivalent probe. The overall reaction route to prepare this bivalent ligand was convergent and efficient, and involved sixteen steps with moderate to good yields. The preliminary biological characterization showed that the bivalent compound 1 retained the pharmacological characteristics of both pharmacophores towards the MOR and the CCR5 respectively with relatively lower binding affinity, which tentatively validated our original molecular design.     

Photoinduced superoxide radical anion and singlet oxygen generation in the presence of novel selenadiazoloquinolones (an EPR Study)

Novel 7‐substituted 6‐oxo‐6,9‐dihydro[1,2,5]selenadiazolo[3,4‐h]quinoline ( SeQ(1–6) ) and 8‐substituted 9‐oxo‐6,9‐dihydro[1,2,5]selenadiazolo[3,4‐f ]quinoline derivatives ( SeQN(1–5) ) with R₇, R₈ = H, COOC₂H₅, COOCH₃, COOH, COCH₃ or CN were synthesized and their spectral characteristics were obtained by UV/Vis spectroscopy. Ultraviolet A photoexcitation of the selenadiazoloquinolones in dimethylsulfoxide or acetonitrile resulted in the formation of paramagnetic species coupled with molecular oxygen activation generating the superoxide radical anion or singlet oxygen, evidenced by electron paramagnetic resonance spectroscopy. The cytotoxic/photocytotoxic impact of selenadiazoloquinolones on murine and human cancer cell lines was demonstrated using the derivative SeQ5 (with R₇ = COCH₃).     

Further investigation of the mechanism of Doxorubicin release from P105 micelles using kinetic models

The kinetics of the release of Doxorubicin from Pluronic P105 micelles during ultrasonication and its subsequent re-encapsulation upon cessation of insonation were investigated. Four mechanisms are proposed to explain the acoustically-triggered Doxorubicin (Dox) release and re-encapsulation from Pluronic P105 micelles. The four mechanisms are: micelle destruction; destruction of cavitating nuclei; reassembly of micelles, and the re-encapsulation of Dox. The first mechanism, the destruction of micelles during insonation, causes the release of Dox into solution. The micelles are destroyed because of cavitation events produced by collapsing nuclei, or bubbles in the insonated solution. The second mechanism, the slow destruction of cavitating nuclei, results in a slow partial recovery phase, when a small amount of Dox is re-encapsulated. The third and fourth mechanisms, the reassembly of micelles and the re-encapsulatin of Dox, are independent of ultrasound. These two mechanism are responsible for maintaining the drug release at a partial level, and for recovery after insonation ceases. A normal distribution was used to describe micellar size. Parameters for the model were determined based upon the best observed fit to experimental data. The resulting model provides a good approximation to experimental data for the release of Dox from Pluronic P105 micelles.     

Fast‐Track,One‐Step E. coli Detection: A Miniaturized Hydrogel Array Permits Specific Direct PCR and DNA Hybridization while Amplification

A timesaving and convenient method for bacterial detection based on one‐step, one‐tube deoxyribonucleic acid (DNA) hybridization on hydrogel array while target gene amplification is described. The hydrogel array is generated by a fast one‐pot synthesis, where N,N′‐dimethylacrylamide/polyethyleneglycol(PEG₁₉₀₀)‐bisacrylamide mixture polymerizes via radical photoinitiation by visible light within 20 min concomitant with in situ capture probe immobilization. These DNA‐functionalized hydrogel droplets arrayed on a planar glass surface are placed in the polymerase chain reaction (PCR) mixture during the thermal amplification cycles. The bacterial cells can be implemented in a direct PCR reaction, omitting the need for prior template DNA extraction. The resulting fluorescence signal is immediately detectable after the end of the PCR (1 h) following one short washing step by microscopy. Therefore a valid signal can be reached within 1.5 h including 10 min for pipetting and placement of the tubes and chips. The performance of this novel hydrogel DNA array was successfully proven with varying cell numbers down to a limit of 10¹Escherichia coli cells.