Search

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that can lead to irreversible loss of vision. Intravenous thrombolysis (IVT) has been used experimentally for its treatment. Our study aimed to evaluate the effect of emergency IVT on CRAO and its impact on visual acuity outcomes. We conducted a retrospective observational study of patients with CRAO. A total of 46 patients with CRAO were analysed; 16 patients received IVT treatment (IVT group) while 30 did not (no-IVT group). Seven patients from the IVT group received IVT early, within 4.5 hours (h) after the onset of symptoms (early-IVT), and 9 patients received it beyond this timeframe (late-IVT). The median time-to-hospital was 8.5 h: 3 h for the IVT group and 24 h for the no-IVT group. The median time-to-treatment was 5 h. The median outcome of visual acuity was 0.05 in the early-IVT, 0.025 in the late-IVT, and 0.01 in the no-IVT group. Among patients who received IVT early, 86% exhibited significant visual improvement. This improvement was four-fold greater compared to all other groups (p = 0.040), including the late-IVT (p = 0.011) and no-IVT groups (p = 0.023). No complications of the treatment were reported. Our study confirms that the administration of IVT treatment for CRAO within the 4.5-h time window is both safe and effective., (© 2023. The Author(s).)

Natural pyrrolobenzodiazepines (PBDs) form a large and structurally diverse group of antitumour microbial metabolites produced through complex pathways, which are encoded within biosynthetic gene clusters. We sequenced the gene cluster of limazepines and proposed their biosynthetic pathway based on comparison with five available gene clusters for the biosynthesis of other PBDs. Furthermore, we tested two recombinant proteins from limazepine biosynthesis, Lim5 and Lim6, with the expected substrates in vitro. The reactions monitored by LC-MS revealed that limazepine biosynthesis involves a new way of 3-hydroxyanthranilic acid formation, which we refer to as the chorismate/DHHA pathway and which represents an alternative to the kynurenine pathway employed for the formation of the same precursor in the biosynthesis of other PBDs. The chorismate/DHHA pathway is presumably also involved in the biosynthesis of PBD tilivalline, several natural products unrelated to PBDs, and its part is shared also with phenazine biosynthesis. The similarities between limazepine and phenazine biosynthesis indicate tight evolutionary links between these groups of compounds.