Impact of Substituents in Tumor Uptake and Fluorescence Imaging Ability of Near‐Infrared Cyanine‐like Dyes

This report presents a simple strategy to introduce various functionalities in a cyanine dye (bis‐indole‐N‐butylsulfonate‐polymethine bearing a fused cyclic chloro‐cyclohexene ring structure), and assess the impact of these substitutions in tumor uptake, retention and imaging. The results obtained from the structural activity relationship (SAR) study demonstrate that certain structural features introduced in the cyanine dye moiety make a remarkable difference in tumor avidity. Among the compounds investigated, the symmetrical CDs containing an amino‐phenyl thioether group attached to a cyclohexene ring system and the two N‐butyl linkers with terminal sulfonate groups in benzoindole moieties exhibited excellent tumor imaging ability in BALB/c mice bearing Colon26 tumors. Compared to indocyanine green (ICG), approved by FDA as a blood pooling agent, which has also been investigated for the use in tumor imaging, the modified CD selected on the basis of SAR study produced enhanced uptake and longer retention in tumor(s). A facile approach reported herein for introducing a variety of functionalities in tumor‐avid CD provides an opportunity to create multi‐imaging modality agent(s). Using a combination of mass spectrometry and absorbance techniques, the photobleaching of one of the CDs was analyzed and significant regioselective photooxidation was observed.     

False EX1 signatures caused by sample carryover during HX MS analyses

Discovery of EX1 kinetics in hydrogen exchange (HX) mass spectrometry (MS) experiments is rare. Proteins follow the EX1 kinetic regime when cooperative unfolding events simultaneously expose multiple residues to solvent such that they all become deuterated together before the region is able to refold. A number of factors can contribute to what we call "false EX1" in which it appears as though EX1 occurs in a protein when it probably does not. One of the contributors to false EX1 is peptide carryover between chromatographic runs. In this work, we explore the origins of peptide carryover in HX MS, describe how carryover causes mass spectra to indicate false EX1 kinetics and then describe an optimized washing protocol that can be used to eliminate peptide carryover. A series of solvent injections was developed and found to efficiently eliminate carryover signatures such that analysis of deuterium incorporation could be reliably followed for two proteins prone to high carryover.     

Subglottic Jet Ventilation for Suspension Microlaryngoscopy

High-frequency subglottic jet ventilation was used in 142 consecutive adults with grade I airways treated with suspension microlaryngoscopy. All cases were managed by the senior anesthesiologist (AP) and the large majority by the senior surgeon (JR), between 2000 and 2002. The laser was used in 30% of cases. There were few complications, none serious, associated with this technique in this series. The subglottic catheter never proved impossible to insert and only needed to be replaced by the supraglottic catheter in two patients because of limitation of visualization of the posterior glottis. The technique was used in a wide variety of surgical pathology from benign hyperfunction-related laryngeal pathology through paralytic vocal fold conditions through papilloma. Advantages and disadvantages over traditional intubation techniques and supraglottic jet ventilation are reviewed, including such issues as ease of intubation/ventilation, surgical exposure/control, maintenance of O2 and CO2 levels, and use in the limited/borderline airway.     

T2* measurements in human brain at 1.5, 3 and 7 T

Measurements have been carried out in six subjects at magnetic fields of 1.5, 3 and 7 T, with the aim of characterizing the variation of T2* with field strength in human brain. Accurate measurement of T2* in the presence of macroscopic magnetic field inhomogeneity is problematic due to signal decay resulting from through-slice dephasing. The approach employed here allowed the signal decay due to through-slice dephasing to be characterized and removed from data, thus facilitating an accurate measurement of T2* even at ultrahigh field. Using double inversion recovery turbo spin-echo images for tissue classification, an analysis of T2* relaxation times in cortical grey matter and white matter was carried out, along with an evaluation of the variation of T2* with field strength in the caudate nucleus and putamen. The results show an approximately linear increase in relaxation rate R2* with field strength for all tissues, leading to a greater range of relaxation times across tissue types at 7 T that can be exploited in high-resolution T2*-weighted imaging.     

Taming the Carboxyl Group for Directed Carbometalation: Observations on the Use of Anions,Dianions and Ester Enolates

Carboxylate anions, dianions and ester enolates provide simultaneous protection and activation for directed carbometalation reactions. Advantage can be taken of the bis‐carbanionic character of the intermediate for further controlled C?C bond forming reactions.     

Aromatische Substanzen

Ohne Zusammenfassung     

Correlation of macromolecular permeability to network characteristics of multivinyl poly(vinyl alcohol) hydrogels

Modulation of the structural parameters of multivinyl hydrogels allows optimization of their permeability, which is a prerequisite for different biomedical applications. However, only a few studies to date have been reported regarding macromolecular diffusion within divinyl and multivinyl systems, and even less provide information about the correlation of diffusion to the network characteristics. Therefore, this study aimed to understand the permeability performance of tailored poly(vinyl alcohol) (PVA) multivinyl hydrogels and correlating it to the network characteristics using two common theories: rubber elasticity and equilibrium swelling. A systematic increase in the number of functional groups per PVA backbone successfully modulated the PVA physicomechanical properties. These modifications resulted in varying the hydrogel permeability performance to solutes of different sizes and shapes. Correlating the network characteristics to macromolecular permeability of hydrogels proved the reliability of applying the equilibrium swelling theory for hydrogel mesh size estimation over the rubber elasticity theory. © 2013 Wiley Periodicals, Inc. J. Polym. Sci. Part B: Polym. Phys. 2014 , 52, 63–72     

Conductive Hydrogels: Mechanically Robust Hybrids for Use as Biomaterials

A hybrid system for producing conducting polymers within a doping hydrogel mesh is presented. These conductive hydrogels demonstrate comparable electroactivity to conventional conducting polymers without requiring the need for mobile doping ions which are typically used in literature. These hybrids have superior mechanical stability and a modulus significantly closer to neural tissue than materials which are commonly used for medical electrodes. Additionally they are shown to support the attachment and differentiation of neural like cells, with improved interaction when compared to homogeneous hydrogels. The system provides flexibility such that biologic incorporation can be tailored for application.