Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic Border Collies

BACKGROUND: Variation in the ABCB1 gene is believed to play a role in drug resistance in epilepsy. HYPOTHESIS/OBJECTIVES: Variation in the ABCB1 gene encoding the permeability-glycoprotein could have an influence on phenobarbital (PB) resistance, which occurs with high frequency in idiopathic epileptic Border Collies (BCs). Animals: Two hundred and thirty-six client-owned BCs from Switzerland and Germany including 25 with idiopathic epilepsy, of which 13 were resistant to PB treatment. METHODS: Prospective and retrospective case-control study. Data were collected retrospectively regarding disease status, antiepileptic drug (AED) therapy, and drug responsiveness. The frequency of a known mutation in the ABCB1 gene (4 base-pair deletion in the ABCB1 gene [c.296_299del]) was determined in all BCs. Additionally, the ABCB1 coding exons and flanking sequences were completely sequenced to search for additional variation in 41 BCs. Association analyses were performed in 2 case-control studies: idiopathic epileptic and control BCs and PB-responsive and resistant idiopathic epileptic BCs. RESULTS: One of 236 BCs (0.4%) was heterozygous for the mutation in the ABCB1 gene (c.296_299del). A total of 23 variations were identified in the ABCB1 gene: 4 in exons and 19 in introns. The G-allele of the c.-6-180T > G variation in intron 1 was significantly more frequent in epileptic BCs resistant to PB treatment than in epileptic BCs responsive to PB treatment (P(raw) = .0025). CONCLUSIONS AND CLINICAL IMPORTANCE: A variation in intron 1 of the ABCB1 gene is associated with drug responsiveness in BCs. This might indicate that regulatory mutations affecting the expression level of ABCB1 could exist, which may influence the reaction of a dog to AEDs.

Writing the Unspeakable: an Ethical Approach to a Traumatized Narrative

This project uses the works of contemporary author Tim O’Brien, whose fiction often performs the trauma of the Vietnam War, to explore new ways of encountering the traumatized text. Informed by Emmanuel Levinas’s ethics of the face, and Sigmund Freud’s and Dominick LaCapra’s work on the narratology of the melancholic and the mourner, I consider the different ways we respond to the suffering Other and explore the paradox that through reading a traumatized narrative empathically we may come face-toface, as it were, with the suffering Other. If this is indeed the case, I reason, then the obligations that are due to the Other are also due to the text itself.