Developmental effects (a, b) and changes in heart beat rate (c–f) after exposition to metandienone. a Regular heart development of medaka embryo after 8 days of development in frontal view (top); after exposition to 50 µM MD, the heart has a tube-like morphology and contractile structures are nearly absent (bottom). b Lateral views as in a. Dotted lines either mark the ventricle or the tube-like heart. Scale bar: 200 µM. (c) Increased heart frequency after exposition to 10 µM MD for 8 days. d–f Increased heart frequency after exposition to 10 µM MD for 2 days in three repeated experiments. Significance code of two-tailed Student’s t test (unpaired): *p value < 0.05; **p value < 0.01; ***p value < 0.001
In anti-doping science, the knowledge of drug metabolism is a prerequisite to identify analytical targets for the detection of misused prohibited substances. As the most obvious way to study xenobiotic metabolism, the administration to human volunteers, faces ethical concerns, there is a need for model systems. In the present study, we investigated...
... This study also demonstrated the importance of mass spectrometry. MS is the current technology of choice for detecting and quantifying proteins and metabolites, as it is adaptable to virtually any type of sample, ranging from cells and neurons to subcellular organelles, tissues, and even whole embryos . Mass spectrometers can directly detect intact proteins, peptides, post-translational modifications, and metabolites with high specificity, usually sub-mDa (sub-ppm) mass accuracy, and the capability for both discovery (untargeted) and targeted studies. ...
Given the non-labile, terminal differentiation of inner-ear sensory cells, preserving their function is critical since sensory cell damage results in irreversible hearing loss. Gentamicin-induced cytotoxicity is one of the major causes of sensory cell damage and consequent sensorineural hearing loss. However, the precise molecular mechanisms and target proteins involved in ototoxicity are still unknown. The objective of the present study was to identify target proteins involved in gentamicin-induced cytotoxicity to better characterize the molecular pathways involved in sensory cell damage following ototoxic drug administration using House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). We identified several unique proteins involved in gentamicin-induced cytotoxicity, expression of which were further confirmed using confocal microscopy. Further investigation of these pathways can inform the design and discovery of novel treatment modalities to prevent sensory cell damage and preserve their function.
Also in 2021/2022, considerable efforts were invested into advancing human sports drug testing programs, recognizing and taking into account existing as well as emerging challenges in anti‐doping, especially with regards to substances and methods of doping specified in the World Anti‐Doping Agency’s 2022 Prohibited List. In this edition of the annual banned‐substance review, literature on recent developments published between October 2021 and September 2022 is summarized and discussed. Focus is put particularly on enhanced analytical approaches and complementary testing options in human doping controls, appreciating the exigence and mission in anti‐doping and, equally, the contemporary ‘new normal’ considering e.g. the athlete’s exposome vs. analytical sensitivity and applicable anti‐doping regulations for result interpretation and management.