Harrison C. Daly, Gonzalo Sampedro, Corentin Bon, Dan Wu, Ghazi Cahill, Roman A. Cahill, Donal F. O’Shea
The use of near-infrared fluorescence for in vivo research and intraoperative clinical imaging is rapidly expanding, with new applications being proposed and developed. While imaging hardware and software have significantly progressed in recent times, the molecular fluorescent agents remain a limiting factor. In this report, the design, synthesis, photophysical characterization and bio-medical imaging assessment of two new NIR-fluorophores based on the BF2-azadipyrromethene fluorophore class are described. Inclusion of dimethylamino substituents on these BF2-azadipyrromethene probes results in very large bathochromic shifts with photophysical measurements showing absorption and emission maxima between 757 and 818 nm within the desired NIR spectra region. Testing of the probes shows that they are suitable for fluorescence imaging with both research and clinical instrumentation. Preclinical imaging assessment shows their suitability as fluorescent markers (tattoos) of lesions for intraoperative identification and lymphatic mapping in ex vivo human colonic tissue. These new clinical wavelength-compatible fluorophores may contribute towards the on-going expansion of medical uses for NIR-fluorescence.
The LC/MS analysis was carried out using Advion Expression® CMS.
Additi Roy Chowdhury, Biswajit Gopal Roy, Saibal Jana, Thomas Weyhermuller, Priyata Banerjee
Novel colorimetric hydrazine-functionalized Schiff base chemoreceptor [N1N3bis(perfluorobenzylidene)isophthalahydrazide] NBPBIH has been prepared for selective detection of F−. In this receptor more NH and CN units are incorporated for better colorimetric responses as compared to systems having lesser number of such units. NBPBIH turns from colorless to dark yellow on exposure to F−. The detection event is well supported by UV–vis, fluorescence, 1H and 19F-NMR like spectrophotometric and cyclic voltammetric studies in DMSO because of enhanced fluorescence responses, higher Stokes shift value and for its less toxic nature compared to other solvents. Quenching of fluorescence is explained with photoinduced electron transfer mechanism (PET). The binding constant of NBPBIH with F− is around 0.84 × 105 M−1 and limit of detection of F− is found 1.42 × 10−5 M. Our concern is also to address fluorosis: an issue related to global health problem, affecting millions of common people. It is noteworthy that the existing diagnostic and treatment options are of huge expenses. As an artefact, chemoreceptor assisted simple prototype for detecting excessive fluoride in sample solution has been designed and developed which has potential and good prospect to be applied as a low cost affordable diagnostic kit for fluorosis in largely affected countries like China, India and several others.
The MS analysis was carried out using Advion Expression® CMS ESI.
M.R. Chae, S.J. Kang, K.P. Lee, B.R. Choi, H.K. Kim, J.K. Park, C.Y. Kim, S.W. Lee
Onion (Allium cepa L.) and quercetin protect against oxidative damage and have positive effects on multiple functional parameters of spermatozoa, including viability and motility. However, the associated underlying mechanisms of action have not yet been identified. The aim of this study was to investigate the effect of onion peel extract (OPE) on voltage-gated proton (Hv1) channels, which play a critical role in rapid proton extrusion. This process underlies a wide range of physiological processes, particularly male fertility. The whole-cell patch-clamp technique was used to record the changes in Hv1 currents in HEK293 cells transiently transfected with human Hv1 (HVCN1). The effects of OPE on human sperm motility were also analyzed. OPE significantly activated the outward-rectifying proton currents in a concentration-dependent manner, with an EC50 value of 30 μg/mL. This effect was largely reversible upon washout. Moreover, OPE induced an increase in the proton current amplitude and decreased the time constant of activation at 0 mV from 4.9 ± 1.7 to 0.6 ± 0.1 sec (n = 6). In the presence of OPE, the half-activation voltage (V1/2 ) shifted in the negative direction, from 20.1 ± 5.8 to 5.2 ± 8.7 mV (n = 6), but the slope was not significantly altered. The OPE-induced current was profoundly inhibited by 10 μm Zn2+ , the most potent Hv1 channel inhibitor, and was also inhibited by treatment with GF109203X, a specific protein kinase C (PKC) inhibitor. Furthermore, sperm motility was significantly increased in the OPE-treated groups. OPE exhibits protective effects on sperm motility, at least partially via regulation of the proton channel. Moreover, similar effects were exerted by quercetin, the major flavonoid in OPE. These results suggest OPE, which is rich in the potent Hv1 channel activator quercetin, as a possible new candidate treatment for human infertility.
The LC/MS analysis was carried out using Advion Expression® CMS.
Aaron L. Smith, Hasse Walum, Fawn Connor-Stroud, Sara M. Freeman, Kiyoshi Inoue, Lisa A. Parr, Mark M. Goodman, Larry J. Young
The physiology of the oxytocin receptor has increasingly become a focus of scientific investigation due to its connection with social behavior and psychiatric disorders with impairments in social funciton. Experimental utilization of small molecule and peptide antagonists for the oxytocin receptor has played a role in deciphering these biological and social behavior connections in rodents. Described herein is the evaluation of a potent and selective oxytocin receptor antagonist, ALS-I-41, and details to consider for its use in nonhuman primate behavioral pharmacology experiments utilizing intranasal or intramuscular administration. The central nervous system penetration and rate of metabolism of ALS-I-41 was investigated via mass spectroscopy analysis of cerebrospinal fluid and plasma in the rhesus macaque after intranasal and intramuscular administration. Positron emission tomography was also utilized with [18F] ALS-I-41 in a macaque to verify observed central nervous system (CNS) penetration and to further evaluate the effects of administration rate on CNS penetration of Sprague-Dawley rats in comparison to previous studies.
The LC/MS analysis was carried out using Advion Expression® CMS.
Advion Interchim Scientific’s range of AVANT®, high performance, liquid chromatography systems can be used standalone with UV and UV/Vis detector options, or with the expression® compact mass spectrometer to provide seamlessly integrated LC/CMS under the full control of Advion Interchim Scientific’s simple, intuitive Mass Express software suite.
Modular, stackable design, with many options, provides custom solutions for both HPLC and UHPLC needs. From the simplest manual injection HPLC to a fully automated, streamlined UHPLC system and everything in-between, the AVANT® series can be configured to fit your analytical requirements and your budget.
The data collected from the analysis on the portable Advion CMS were treated in exactly the same way as the data collected from the Waters LCT and although the mass resolution and sensitivity of the two instruments is different the same clustering patterns were seen in the PCA scores plots. The PCA loadings plots also showed the same patterns with the same major 385.4 mass bin responsible for the separation of the classes seen in the scores plots.
The findings are important because they suggest that metabolite profiling could offer an accurate, and time-effective tool for identifying women at increased risk of HPV persistence. Current screening for cervical cancer risk relies, as a first step, on a cytological assessment which can be difficult to classify at the low-grade end of cervical cell abnormality and currently there is no screening tool for predicting HPV persistence. Metabolite profiling therefore has the potential to improve existing screening methods for cell abnormality and to supplement information about HPV positivity; the critically important risk factor for cervical cancer.
ABSTRACT: Large-scale metabolic profiling requires the development of novel economical high-throughput analytical methods to facilitate characterization of systemic metabolic variation in population phenotypes. We report a fit-forpurpose direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) method with time-of-flight detection for rapid targeted parallel analysis of over 40 urinary metabolites. The newly developed 2 min infusion method requires <10 μL of urine sample and generates high-resolution MS profiles in both positive and negative polarities, enabling further data mining and relative quantification of hundreds of metabolites. Here we present optimization of the DI-nESI-HRMS method in a detailed step-by-step guide and provide a workflow with rigorous quality assessment for large-scale studies.
From the Journal of Proteome Research, Published February 2017
The early stages of nonalcoholic fatty liver disease (NAFLD) are characterized by the accumulation of fat in the liver (steatosis). This can lead to cell injury and inflammation resulting in nonalcoholic steatohepatitis (NASH). To determine whether lipid profiling of liver tissue can identify metabolic signatures associated with disease presence and severity, we explored liquid extraction surface analysis mass spectrometry (LESA−MS, Advion TriVersa NanoMate with LESA PLUS) as a novel sampling tool. Using LESA−MS, lipids were extracted directly from the surface of ultrathin slices of liver tissue prior to detection by high-resolution mass spectrometry (MS).
We compared the data obtained by LESA− MS to that from liquid chromatography (LC)− MS and matrix-assisted laser desorption ionization MS. Advantages of LESA− MS include rapid analysis, minimal sample preparation, and high lipid coverage.
Furthermore, since tissue slices are routinely used for diagnostics in clinical settings, LESA− MS is ideally placed to complement traditional histology. Overall LESA− MS is found to be a robust, fast, and discriminating approach for determining NAFLD presence and severity in clinical samples.
N units are incorporated for better colorimetric responses as compared to systems having lesser number of such units. NBPBIH turns from colorless to dark yellow on exposure to F−. The detection event is well supported by UV–vis, fluorescence, 1H and 19F-NMR like spectrophotometric and cyclic voltammetric studies in DMSO because of enhanced fluorescence responses, higher Stokes shift value and for its less toxic nature compared to other solvents. Quenching of fluorescence is explained with photoinduced electron transfer mechanism (PET). The binding constant of NBPBIH with F− is around 0.84 × 105 M−1 and limit of detection of F− is found 1.42 × 10−5 M. Our concern is also to address fluorosis: an issue related to global health problem, affecting millions of common people. It is noteworthy that the existing diagnostic and treatment options are of huge expenses. As an artefact, chemoreceptor assisted simple prototype for detecting excessive fluoride in sample solution has been designed and developed which has potential and good prospect to be applied as a low cost affordable diagnostic kit for fluorosis in largely affected countries like China, India and several others.
