Identification of fungal trehalose for the diagnosis of invasive candidiasis by mass spectrometry

Fungal infections are a worldwide health problem, especially in immunocompromised patients and patients with chronic disorders. Invasive candidiasis, caused mainly by C. albicans , is among the most common fungal diseases.

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Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02268-19 ◽

2019 ◽

Vol 64 (3) ◽

Cited By ~ 3

Author(s):

Annie Lee ◽

Brendan Prideaux ◽

Matthew Zimmerman ◽

Claire Carter ◽

Stephen Barat ◽

...

Keyword(s):

Mass Spectrometry ◽

Mouse Model ◽

Invasive Candidiasis ◽

Drug Exposure ◽

Fungal Infections ◽

Therapeutic Option ◽

Repeated Treatment ◽

Ionization Mass ◽

Drug Concentrations ◽

Abdominal Candidiasis

ABSTRACT Ibrexafungerp (IBX), formerly SCY-078, is a novel, oral and intravenous, semisynthetic triterpenoid glucan synthase inhibitor in clinical development for treating multiple fungal infections, including invasive candidiasis. Intra-abdominal candidiasis (IAC) is one of the most common types of invasive candidiasis associated with high mortality largely due to poor drug exposure in infected lesions. To better understand the potential of IBX to treat such infections, we investigated its penetration at the site of infection. Using matrix-assisted laser desorption ionization–mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed high-pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we investigated tissue distribution and lesion-specific drug exposure of IBX in a clinically relevant IAC mouse model. After a single-dose treatment, IBX quickly distributed into tissues and efficiently accumulated within lesions. Drug concentrations of IBX within the liver abscesses were almost 100-fold higher than the serum concentration. In addition, drug penetration after repeated treatment of IBX was compared with micafungin. IBX exhibited robust and long-lasting lesion penetration after repeated treatment. These data indicate that IBX penetrates into intra-abdominal abscesses highly efficiently and holds promise as a potential therapeutic option for IAC patients.

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How SIMS microscopy can be used in medicine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100132649 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1602-1603

Author(s):

Philippe Fragu

Keyword(s):

Mass Spectrometry ◽

Biomedical Applications ◽

Secondary Ion Mass Spectrometry ◽

Chemical Elements ◽

Biological Applications ◽

The Past ◽

Potential Source ◽

Secondary Ion ◽

Chemical Integrity ◽

Scientific Endeavour

The identification, localization and quantification of intracellular chemical elements is an area of scientific endeavour which has not ceased to develop over the past 30 years. Secondary Ion Mass Spectrometry (SIMS) microscopy is widely used for elemental localization problems in geochemistry, metallurgy and electronics. Although the first commercial instruments were available in 1968, biological applications have been gradual as investigators have systematically examined the potential source of artefacts inherent in the method and sought to develop strategies for the analysis of soft biological material with a lateral resolution equivalent to that of the light microscope. In 1992, the prospects offered by this technique are even more encouraging as prototypes of new ion probes appear capable of achieving the ultimate goal, namely the quantitative analysis of micron and submicron regions. The purpose of this review is to underline the requirements for biomedical applications of SIMS microscopy.Sample preparation methodology should preserve both the structural and the chemical integrity of the tissue.

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Imaging of Al-Li-Cu alloys with a Scanning Ion Microprobe

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100135174 ◽

1990 ◽

Vol 48 (2) ◽

pp. 314-315

Author(s):

K.K. Soni ◽

D.B. Williams ◽

J.M. Chabala ◽

R. Levi-Setti ◽

D.E. Newbury

Keyword(s):

Mass Spectrometry ◽

Secondary Ion Mass Spectrometry ◽

Equilibrium Phase ◽

Icosahedral Symmetry ◽

Ion Microprobe ◽

X Ray ◽

Cu Alloys ◽

Two Phases ◽

The University ◽

Secondary Ion

In contrast to the inability of x-ray microanalysis to detect Li, secondary ion mass spectrometry (SIMS) generates a very strong Li+ signal. The latter’s potential was recently exploited by Williams et al. in the study of binary Al-Li alloys. The present study of Al-Li-Cu was done using the high resolution scanning ion microprobe (SIM) at the University of Chicago (UC). The UC SIM employs a 40 keV, ∼70 nm diameter Ga+ probe extracted from a liquid Ga source, which is scanned over areas smaller than 160×160 μm2 using a 512×512 raster. During this experiment, the sample was held at 2 × 10-8 torr.In the Al-Li-Cu system, two phases of major importance are T1 and T2, with nominal compositions of Al2LiCu and Al6Li3Cu respectively. In commercial alloys, T1 develops a plate-like structure with a thickness <∼2 nm and is therefore inaccessible to conventional microanalytical techniques. T2 is the equilibrium phase with apparent icosahedral symmetry and its presence is undesirable in industrial alloys.

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Applications of Time-OF-Flight Secondary Ion Mass Spectrometry (TOF-SIMS)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100135149 ◽

1990 ◽

Vol 48 (2) ◽

pp. 308-309

Author(s):

Bruno Schueler ◽

Robert W. Odom

Keyword(s):

Mass Spectrometry ◽

Secondary Ion Mass Spectrometry ◽

Structural Information ◽

Time Of Flight ◽

Biological Tissues ◽

Polymer Surfaces ◽

Tof Sims ◽

Secondary Ions ◽

Ion Mass Spectrometry ◽

Secondary Ion

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) provides unique capabilities for elemental and molecular compositional analysis of a wide variety of surfaces. This relatively new technique is finding increasing applications in analyses concerned with determining the chemical composition of various polymer surfaces, identifying the composition of organic and inorganic residues on surfaces and the localization of molecular or structurally significant secondary ions signals from biological tissues. TOF-SIMS analyses are typically performed under low primary ion dose (static SIMS) conditions and hence the secondary ions formed often contain significant structural information.This paper will present an overview of current TOF-SIMS instrumentation with particular emphasis on the stigmatic imaging ion microscope developed in the authors’ laboratory. This discussion will be followed by a presentation of several useful applications of the technique for the characterization of polymer surfaces and biological tissues specimens. Particular attention in these applications will focus on how the analytical problem impacts the performance requirements of the mass spectrometer and vice-versa.

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