Reclassification of Pregabalin in the UK: Has It Made a Difference in Deaths?
The effect of TRV027 on coagulation in COVID 19: A pilot randomized, placebo-controlled controlled trial
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COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear, one hypothesis is that loss of Angiotensin Converting Enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin II accumulation, loss of angiotensin-1-7 and...
Radiolabelling Pt-based quadruplex DNA binders via click chemistry.
Guanine-rich sequences of DNA and RNA can fold into intramolecular tetra-helical assemblies known as G-quadruplexes (G4). Their formation in vivo has been associated to a range of biological functions and therefore they have been identified as potential drug targets. Consequently, a broad range of small molecules have been developed to target G4s. ...
The endocannabinoid analgesic entourage effect: investigations in cultured DRG neurons
Background: The endocannabinoid 2-Arachidonyl glycerol (2-AG) exerts dose-related anti-nociceptive effects, which are potentiated by the related but inactive 2-palmitoyl glycerol (2-PG) and 2-linoleoyl glycerol (2-LG). This potentiation of analgesia and other in vivo measures was described as the “entourage effect”. We investigated this effect on T...
Identification of inhibitors of the Schistosoma mansoni VKR2 kinase domain
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Schistosomiasis is a neglected tropical disease caused by parasitic flatworms. Current treatment relies on just one partially effective drug, praziquantel (PZQ). Schistosoma mansoni Venus Kinase Receptors 1 and 2 (SmVKR1 and SmVKR2) are important for parasite growth and egg production, and are potential targets for combating schistosomiasis. VKRs c...
Assessing the clinical value of faecal bile acid profiling to predict recurrence in primary Clostridioides difficile inf...
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Background: Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis. Aims: To define stool BA dynamics in patients with primary CDI and ...
No new ‘mabs’ in medicine – New nomenclature for monoclonal antibodies
Conundrum of clinical QTc monitoring
Generalised weibull model-based approaches to detect non-constant hazard to signal adverse drug reactions in longitudina...
Pharmacovigilance is the process of monitoring the emergence of harm from a medicine once it has been licensed and is in use. The aim is to identify new adverse drug reactions (ADRs) or changes in frequency of known ADRs. The last decade has seen increased interest for the use of electronic health records (EHRs) in pharmacovigilance. The causal mec...
Understanding the stabilizing effect of histidine on mAb aggregation: a molecular dynamics study.
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Histidine, a widely used buffer in monoclonal antibody (mAb) formulations, is known to reduce antibody aggregation. While experimental studies suggest a nonelectrostatic, nonstructural (relating to secondary structure preservation) origin of the phenomenon, the underlying microscopic mechanism behind the histidine action is still unknown. Understan...
