Trends in tricyclic antidepressant prescribing and poisoning in England and Wales 2016-2020.

Aims: Tricyclic antidepressants (TCAs) are commonly prescribed despite no longer being a NICE-recommended first-line treatment for depression and their recognized toxicity in overdose. This study examined prescribing, mortality, hospital admissions and clinical TCA data to quantify the use and impact of TCAs in England and Wales.

Methods: Primary care prescription data for the eight TCAs currently licensed in England and Wales were analysed alongside hospital admission and mortality data relating to TCAs over the study period (January 2016-December 2020 inclusive).

A case series of ibogaine toxicity reported to the United Kingdom National Poisons Information Service (NPIS) over a 10-year period.

Introduction: Ibogaine is a psychoactive alkaloid derived from the root bark of the West African shrub . It is not licensed in the United Kingdom but is used by individuals to alleviate drug or alcohol use.

Methods: A retrospective analysis of telephone enquiries involving ibogaine between 1 January 2012 and 31 December 2022 to the United Kingdom National Poisons Information Service was performed.

Phosphodiesterase inhibition restoreshypoxia-induced cerebrovascular dysfunction subsequent to improved systemic redox homeostasis: A randomized, double-blind, placebo-controlled crossover study.

To what extent sildenafil, a selective inhibitor of the type-5 phosphodiesterase modulates systemic redox status and cerebrovascular function during acute exposure to hypoxia remains unknown. To address this, 12 healthy males (aged 24 ± 3 y) participated in a randomized, placebo-controlled crossover study involving exposure to both normoxia and acute (60 min) hypoxia (Fi = 0.14), followed by oral administration of 50 mg sildenafil and placebo (double-blinded).

OTUD6B regulates KIFC1-dependent centrosome clustering and breast cancer cell survival.

Cancer cells often display centrosome amplification, requiring the kinesin KIFC1/HSET for centrosome clustering to prevent multipolar spindles and cell death. In parallel siRNA screens of deubiquitinase enzymes, we identify OTUD6B as a positive regulator of KIFC1 expression that is required for centrosome clustering in triple-negative breast cancer (TNBC) cells. OTUD6B can localise to centrosomes and the mitotic spindle and interacts with KIFC1.

Macrophage Therapy for Acute Liver Injury (MAIL): a study protocol for a phase 1 randomised, open-label, dose-escalation study to evaluate safety, tolerability and activity of allogeneic alternatively activated macrophages in patients with paracetamol-induced acute liver injury in the UK.

Introduction: Acute liver failure (ALF) has no effective treatment other than liver transplantation and is commonly caused by paracetamol overdose. New treatments are needed to treat and prevent ALF. Alternatively-activated macrophages (AAMs) can promote resolution of liver necrosis and stimulate hepatocyte proliferation.