multiplex-therapeutic-drug-monitoring-isotope-dilution-hplc-msms

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

There is an ever-increasing demand for the therapeutic drug monitoring of antibiotics in many clinical facilities, particularly with regard to the ...

LMU Munich

Long noncoding RNA-MicroRNA pathway controlling nuclear factor IA, a novel atherosclerosis modifier gene.

The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of CXCL12/CXCR4 has only been implied through pharmacological intervention, in particular, because the somatic deletion of the  gene in mice is embryonically lethal. Moreover, cell-specific effects of CXCR4 in the arterial wall and underlying mechanisms remain elusive, prompting us to investigate the relevance of CXCR4 in vascular cell types for atheroprotection.

Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity: Evidence From Mouse and Human Studies.

The ingredients of Actovegin were analyzed and its effects on the muscle cell proliferation were investigated. C2C12 myoblasts were cultured in medium. Actovegin was added in five different concentrations (1, 5, 25, 125, and 250 µg) to the differentiation medium. The formations of proliferation factor Ki67 and myosin heavy chains were measured by immunofluorescence. The first primary antibody was anti-Ki67 and anti-Mf20. Cells were washed and treated with the second fluorochrome. Thirty-one Actovegin ingredients were found to contain significantly higher concentrations and twenty-nine ingredients were found to contain significantly lower concentrations, compared to the mean ranges as described in the literature for the normal physiological concentrations in human adult serum/plasma. A significant increase in the formation of Ki67 was observed in Actovegin groups, compared to controls. The mean area of myotubes was significantly increased in Actovegin groups. A significant decrease in the number of myotubes was observed. An increased myotube size (fusion) was observed. The intensity of Mf20 was significantly increased in Actovegin groups. It could be demonstrated that Actovegin contains many physiological substances in significantly higher and some in lower concentrations compared to human adult serum. Furthermore, it could be shown that Actovegin improves muscle cell proliferation.

Comprehensive Analytics of Actovegin® and Its Effect on Muscle Cells.

Clinical analysis of blood is the most widespread diagnostic procedure in medicine, and blood biomarkers are used to categorize patients and to support treatment decisions. However, existing biomarkers are far from comprehensive and often lack specificity and new ones are being developed at a very slow rate. As described in this review, mass spectrometry (MS)-based proteomics has become a powerful technology in biological research and it is now poised to allow the characterization of the plasma proteome in great depth. Previous "triangular strategies" aimed at discovering single biomarker candidates in small cohorts, followed by classical immunoassays in much larger validation cohorts. We propose a "rectangular" plasma proteome profiling strategy, in which the proteome patterns of large cohorts are correlated with their phenotypes in health and disease. Translating such concepts into clinical practice will require restructuring several aspects of diagnostic decision-making, and we discuss some first steps in this direction.

Revisiting biomarker discovery by plasma proteomics.

Protein-coding and noncoding genes in eukaryotes are typically expressed as linear messenger RNAs, with exons arranged colinearly to their genomic order. Recent advances in sequencing and in mapping RNA reads to reference genomes have revealed that thousands of genes express also covalently closed circular RNAs. Many of these circRNAs are stable and contain exons, but are not translated into proteins. Here, we review the emerging understanding that both, circRNAs produced by co- and posttranscriptional head-to-tail "backsplicing" of a downstream splice donor to a more upstream splice acceptor, as well as circRNAs generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions in eukaryotes. We describe how circRNAs impact gene expression of their host gene locus by affecting transcriptional initiation and elongation or splicing, and how they partake in controlling the function of other molecules, for example by interacting with microRNAs and proteins. We conclude with an outlook how circRNA dysregulation affects disease, and how the stability of circRNAs might be exploited in biomedical applications.

Daniel Teupser

Institute of Laboratory Medicine,
University Hospital,
Institute of Laboratory Medicine, University Hospital

LMU Munich

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Daniel Teupser

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Institute of Laboratory Medicine,University Hospital,Institute of Laboratory Medicine, University Hospital

LMU Munich

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Institute of Laboratory Medicine,
University Hospital,
Institute of Laboratory Medicine, University Hospital