Biomarkers and Clinical Toxicology - Research Groups
Group in Basel
Drs. M. Haschke, MD & A. Scholer, PhD |
Lab-based clinical toxicology I (Manuel Haschke, Michael Bodmer, André Scholer, co-applicants)
During the last years, we have developed a library containing the fragmentation patterns of the most often observed toxins in patients attending the emergency unit of the University Hospital of Basel. This library contains, among others, the fragmentation patterns of most antidepressives, neuroleptics, benzodiazepines and opiates. The library is suitable for rapid detection and quantification of unknown toxins in intoxicated patients. This library needs completion and maintenance to fulfill its duties. We have developed an expert system for the localization of renal tubular damage using the protein excretion pattern in urine (24a). A similar system will be developed for the rapid diagnosis of intoxications in patients.
Groups in Geneva
Prof. Denis Hochstrasser, MD, Vice Dean |  |
Lab based clinical toxicology II (Denis Hochstrasser, main applicant; Marc Fathi; Jean-Luc Veuthey, co-applicants)
Adverse drug reactions (ADR) present an important clinical issue, as illustrated by some studies conducted in the United States of America: per year and for this country only, ADRs are responsible of more than 2 million hospitalizations, cause the death of more than 100 thousands people and generate 1.5 to 4 billion dollars of costs to the society. Careful drug monitoring has been reported to reduce some of these ADRs (59-61). The Remedi® system is an automated HPLC-UV screening instrument, including sample preparation, with a data base, that we have extended, of about now thousand compounds. It is a major tool in clinical toxicology to screen for compounds involved in ADRs and intoxication. The system allows identification of a wide range of compounds, short turn-around-time (about 20 minutes) and operate 24 hours a day. We are currently adapting the system to LC-MS-MS separation and detection. However, some drugs irreversibly bind to blood proteins and may thus be present in blood but undetectable under their free form. In addition, ADRs could be identified by or even due to drug-induced post-translational modifications (PTMs) on several blood proteins. Therefore, monitoring these drug-protein bindings and particularly PTMs of blood proteins may also be essential to diagnose and to prevent some ADRs and intoxication (62-64).
Prof. Pierre Dayer, MD, Medical Director |
Advanced Clinical Toxicology (Pierre Dayer, Jules Desmeules, Michel Rossier, co-applicants)
An important part of the interindividual variability in the response to pharmacological treatments is due to the presence of polymorphisms in genes coding for proteins involved in the metabolism, the transport or the action of therapeutic drugs. The Laboratory of Toxicogenetics at the Service of Laboratory Medicine currently performs genotyping analysis of several genes known to directly influence drug pharmacokinetics, transportation or action (CYP450 2D6, 2C9, 2C19, 2E1, NAT2, MDR1, VKORC1). Various methods based on PCR, from restriction fragment length polymorphism (RFLP) to real-time PCR analysis, have been introduced in the laboratory for analyzing separately multiple polymorphisms. Since 4-5 years, a great effort has been made for employing a more global approach based on DNA microarrays. The introduction of an Affymetrix platform in the lab has allowed determining simultaneously 33 different alleles of the CYP450 2D6 gene instead of the five previously assessed individually (65-68).
Last Updated on Thursday, 25 March 2010 15:36 Created: Tuesday, 07 April 2009 12:57
