0000000000880588
AUTHOR
Markus Schmid
Liver failure under valproic acid
Valproic acid (VPA, 2-propylvaleric acid) is originally an antiepileptic drug, which has been in use for more than 30 years in over 100 countries. The clinical application of VPA has expanded in the last years. Approval has been granted by the FDA for treatment of migraine and cluster headache in 1996, and for treatment of mania and long-term prophylaxis of bipolar affective disorder in 1995. In ongoing studies, VPA has been reported to inhibit growth of several types of cancer cells; in addition, effects on neurodegeneration, and on virus replication in HIV infection have been demonstrated potentially expanding the application of VPA in the future. Despite a good tolerability of the drug, …
Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation
Epitope density and organization have been shown to be important factors for B cell activation in many animal model systems. However, it has been difficult to separate the role of antigen organization from the role of local antigen concentrations because highly organized antigens are usually particulate whereas non-organized antigens are more soluble. Hence, highly organized and non-organized antigens may interact with different cell types and in different locations within lymphoid organs. In order to assess the role of antigen organization in regulating B cell responses, we immunized mice with highly repetitive virus-like particles, which exhibit different epitope densities covalently atta…
Non-fatal and fatal liver failure associated with valproic acid.
Little is known about hepatotoxicity associated with valproic acid (VPA), a widely used substance in neuropsychiatry.All reported cases to the German Federal Institute for Drugs and Medical Devices between 1993 and 2009 of VPA-induced serious hepatic side effects were evaluated.A total of 132 cases of serious VPA-associated liver failure were identified. Approximately one third (34.8%) occurred under VPA monotherapy, while the majority was seen with VPA plus co-medication, most frequently antiepileptics (34.8%) and benzodiazepines (16.7%). A subgroup of 34 cases (25.8%) had a fatal outcome, the largest number reported to date. Of these, 32.4% were under VPA monotherapy and 67.6% under VPA p…