Potential of measured relative shifts in collision cross section values for biotransformation studies.

Ion mobility spectrometry-mass spectrometry (IMS-MS) separates gas phase ions due to differences in drift time from which reproducible and analyte-specific collision cross section (CCS) values can be derived. Internally conducted in vitro and in vivo metabolism (biotransformation) studies indicated repetitive shifts in measured CCS values (CCS) between parent drugs and their metabolites. Hence, the purpose of the present article was (i) to investigate if such relative shifts in CCS were biotransformation-specific and (ii) to highlight their potential benefits for biotransformation studies.

Double Trap Interface: A novel gas interface for high throughput analysis of biomedical samples by AMS.

Although Accelerator Mass Spectrometry (AMS) offers unparalleled sensitivity by investigating the fate of C-labeled compounds within the organism, its widespread use in ADME (absorption, distribution, metabolism, excretion) studies is limited. Conventional approaches based on Liquid Scintillation Counting (LSC) are still preferred, in particular because of complexity and costs associated with AMS measurements. Progress made over the last decade towards more compact AMS systems increased the interest in a combustion-based AMS approach allowing the analysis of samples in gaseous form.

Evaluation of cAMS for C microtracer ADME studies: opportunities to change the current drug development paradigm.

Aim: Although regulatory guidances require human metabolism information of drug candidates early in the development process, the human mass balance study (or hADME study), is performed relatively late. hADME studies typically involve the administration of a C-radiolabelled drug where biological samples are measured by conventional scintillation counting analysis. Another approach is the administration of therapeutic doses containing a C-microtracer followed by accelerator mass spectrometry (AMS) analysis, enabling hADME studies completion much earlier.

The emerging microduplication 3q13.31: Expanding the genotype-phenotype correlations of the reciprocal microdeletion 3q13.31 syndrome.

Microdeletion and microduplication syndromes are well-known causes of developmental delay and/or malformations of differing severity. It was recently reported that a microdeletion at the 3q13.31 locus is associated with a new syndrome combining developmental delay, postnatal overgrowth and dysmorphic features.

The impact of early human data on clinical development: there is time to win.

Modern accelerator mass spectrometry (AMS) methods enable the routine application of this technology in drug development. By the administration of a (14)C-labelled microdose or microtrace, pharmacokinetic (PK) data, such as mass balance, metabolite profiling, and absolute bioavailability (AB) data, can be generated easier, faster, and at lower costs. Here, we emphasize the advances and impact of this technology for pharmaceutical companies.

ADME studies of [5-(3)H]-2'-O-methyluridine nucleoside in mice: a building block in siRNA therapeutics.

The chemical modification 2'-O-methyl of nucleosides is often used to increase siRNA stability towards nuclease activities. However, the metabolic fate of modified nucleosides remains unclear. Therefore, the aim of this study was to determine the mass balance, pharmacokinetic, and absorption, distribution, metabolism, and excretion (ADME)-properties of tritium-labeled 2'-O-methyluridine, following a single intravenous dose to male CD-1 mice.

Mosaicplasty for femoral osteochondritis dissecans.

The authors describe a surgical mosaicplasty technique, with an anterior surgical dislocation approach without trochanterotomy, for osteochondritis dissecans of the hip. A graft was taken from the lateral condyle of the knee. Two adolescents underwent this procedure with good results.

Absorption, distribution, metabolism, and excretion (ADME) of ¹⁴C-sonidegib (LDE225) in healthy volunteers.

Purpose: The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects.

Methods: Six subjects received a single oral dose of 800 mg ¹⁴C-sonidegib (74 kBq, 2.0 µCi) under fasting conditions.

Metabolism of patupilone in patients with advanced solid tumor malignancies.

A phase 1, open-label, non-randomized, single center study was conducted to determine the pharmacokinetics, distribution, metabolism, elimination, and mass balance of patupilone in patients with advanced solid tumors. Five patients with advanced solid tumors received 10 mg/m(2) (1.1 MBq) of (14) C-radiolabeled patupilone at cycle 1 as a 20-minute intravenous infusion every 3 weeks until disease progression.

Diagnostic, staging, and grading of urothelial carcinomas from urine: performance of BCA-1, a mini-array comparative genomic hybridisation-based test.

Background: Cytogenetic abnormalities occur at an early stage of bladder urothelial carcinomas (BUC), and their frequency increases as the cancer becomes more advanced.

Objective: To assess the diagnostic performance of a test based on cytogenetic abnormalities to diagnose, stage, and grade BUC from the urine.

Design, Setting, And Participants: We used a 341 bacterial artificial chromosome (BAC) comparative genomic hybridisation (CGH)-array chip (BCA-1) designed to include loci affected in BUC.

[Misleading diagnosis of a migratory epigastric pain in mobile emergency units: spontaneous rupture of the oesophagus].

The local mobile emergency unit took charge of a patient who suffered from a sudden migratory epigastric pain in the back. The clinical picture led to an initial diagnosis of an aorta dissection. Admitted to Grenoble UH's emergency unit, the radiological examination ruled out a cardiovascular pathology.

Maximum capacities for adsorption of phenanthrene in the slowly and very slowly desorbing domains in nineteen soils and sediments.

The maximum amounts of phenanthrene that can be taken up in both the slowly desorbing domain and the very slowly desorbing domain of 19 soils and sediments were determined by measuring the desorption of phenanthrene added at high loadings associated with equilibrium concentrations in water close to the aqueous solubility of phenanthrene. For two soils and one sediment, literature values for Langmuir phenanthrene adsorption capacities were available. These values were almost equal to the sum of the maximum amounts taken up in the slowly and in the very slowly desorbing domain.

Complex translocation (8;12;21): a new variant of t(8;21) in acute myeloid leukemia.

Variants of the t(8;21)(q22;q22) involving chromosomes 8, 21, and other chromosomes account for approximately 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. In this paper, we report a case of AML-M2 with a t(8;12;21)(q22;p12 approximately p13;q22) associated with chromosomal abnormalities, including loss of the Y chromosome and trisomy 8q22 approximately qter. Using a dual-color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrated an ETO/AML1 fusion signal on the derivative chromosome 8.

Alternative pathways of MYCN gene copy number increase in primary neuroblastoma tumors.

Neuroblastomas, tumors of the sympathetic nervous system, account for 7-10% of the cancers of childhood. Genetic studies have shown, and this study has confirmed, that neuroblastomas are very heterogeneous; no single genetic change common to all neuroblastomas has yet been identified. One genetic aberration found frequently in this pediatric tumor is MYCN gene amplification.