Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats.

Here, we demonstrate detection by mass spectrometry of an intact protein-drug complex directly from liver tissue from rats that had been orally dosed with the drug. The protein-drug complex comprised fatty acid binding protein 1, FABP1, non-covalently bound to the small molecule therapeutic bezafibrate. Moreover, we demonstrate spatial mapping of the [FABP1+bezafibrate] complex across a thin section of liver by targeted mass spectrometry imaging. This work is the first demonstration of in situ mass spectrometry analysis of a non-covalent protein-drug complex formed in vivo and has implications for early stage drug discovery by providing a route to target-drug characterization directly from the physiological environment.

Persistent Atrial Fibrillation Ablation using the Tip-Versatile Ablation Catheter.

BACKGROUND: The mechanisms by which persistent atrial fibrillation (PsAF) develops are incompletely understood. Consequently, the optimal strategy for the ablative management of PsAF remains debated. Current methods are often time consuming, complex and non-reproducible. We assessed the Tip-Versatile Ablation Catheter (T-VAC) technique, a rapidly delivered, empirical technique based on the box-set concept using duty-cycled linear catheter ablation technology. METHODS: Forty-four procedures in 40 patients undergoing PsAF ablation with the novel technique were prospectively entered onto a database: 27 de novo. Primary endpoint was freedom from arrhythmia at over two-year follow-up. Secondary endpoints were time to first arrhythmia recurrence, freedom from atrial fibrillation (AF) on and off antiarrhythmic drugs (AAD), procedural and fluoroscopy duration and complication rate. RESULTS: At mean follow-up of 33 months, absolute freedom from arrhythmia recurrence was 45% in the de novo group. Overall, at 33 (IQR 24-63) months, 60% of de novo patients were in sustained normal sinus rhythm and a further 15% reported only occasional paroxysms of AF at long-term follow-up. Procedure time was 192±25 mins, total energy delivered 2239±883s and fluoroscopy time was 60±10mins. CONCLUSION: In selected patients with persistent AF, a long-term rate of 60% arrhythmia free survival off AAD can be achieved using this novel T-VAC technique.

Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats.

Here, we demonstrate detection by mass spectrometry of an intact protein-drug complex directly from liver tissue from rats that had been orally dosed with the drug. The protein-drug complex comprised fatty acid binding protein 1, FABP1, non-covalently bound to the small molecule therapeutic bezafibrate. Moreover, we demonstrate spatial mapping of the [FABP1+bezafibrate] complex across a thin section of liver by targeted mass spectrometry imaging. This work is the first demonstration of in situ mass spectrometry analysis of a non-covalent protein-drug complex formed in vivo and has implications for early stage drug discovery by providing a route to target-drug characterization directly from the physiological environment.