British Journal of Pharmacology

BACKGROUND AND PURPOSE: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic β cells activates the CRF2 receptor (CRF2 R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. EXPERIMENTAL APPROACH: Here, we used Arrb1-/- , Arrb2-/- , Gsfl/fl and Gqfl/fl knockout mice, the G11 -shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs , G11 and β-arrestin1 to CRF2 R contributed to UCN3-induced SST secretion in pancreatic δ cells...

AIMS: While diagnostic codes from administrative health data might be a valuable source to identify adverse drug events (ADEs), their ability to identify unintended harms remains unclear. We validated claims-based diagnosis codes for ADEs based on events identified in a prospective cohort study and assessed whether key attributes predicted their documentation in administrative data. METHODS: This was a retrospective analysis of 3 prospective cohorts in British Columbia, from 2008 to 2015 (n = 13 969)...

BACKGROUND AND PURPOSE: An estimated 40% of patients with erectile dysfunction have a poor prognosis for improvement with currently available treatments. The present study investigated whether a newly developed monoamine transport inhibitor, IP2015, improves erectile function. EXPERIMENTAL APPROACH: We investigated the effects of IP2015 on monoamine uptake and binding, erectile function in rats and diabetic mice and the effect on corpus cavernosum contractility...

BACKGROUND AND PURPOSE: At present, the inhibition of staphyloxanthin biosynthesis has emerged as a prominent strategy in combating methicillin-resistant Staphylococcus aureus (MRSA) infection. Nonetheless, there remains a limited understanding regarding the bio-structural characteristics of staphyloxanthin biosynthetic enzymes, as well as the molecular mechanisms underlying the interaction between inhibitors and proteins. Furthermore, the functional scope of these inhibitors is relatively narrow...

AIMS: We aimed to investigate antibacterial-induced thrombocytopenia using the China Hospital Pharmacovigilance System (CHPS) in conjunction with Visual Basic for Applications (VBA). METHODS: Between September 2011 and December 2022, a 2-phase workflow was employed to identify antibacterial-induced thrombocytopenia, including preliminary screening in phase (I) conducted by CHPS algorithms and causality assessment by trained pharmacists in phase (II) using VBA. The incidence of thrombocytopenia in each antibacterial was calculated, and comparisons were performed between paediatric and adult patients...

BACKGROUND AND PURPOSE: The discovery of new bromo- and extra-terminal inhibitors presents new drugs to treat osteoarthritis (OA). EXPERIMENTAL APPROACH: The new drug, BBC0403, was identified in the DNA-encoded library screening system by searching for compounds that target BRD (bromodomain-containing) proteins. The binding force with BRD proteins was evaluated using time-resolved fluorescence energy transfer (TR-FRET) and binding kinetics assays. Subsequently, in vitro and ex vivo analyses demonstrated the effects of the BRD2 inhibitor, BBC0403, on OA...

We here present a case providing valuable insights for clinicians who deliver care to patients identifying as transgender or nonbinary. A 30-year-old trans woman presented to sexual health services requesting a routine sexual health screen and was subsequently diagnosed with HIV and syphilis. She started antiretrovirals for HIV (bictegravir/tenoforvir alafenamide/emtricitabine) 12 days later and was treated with benzathine penicillin G. The patient also had a positive tuberculosis (TB) ELIspot blood test result and further investigations proved the presence of active TB in the chest with mediastinal involvement...

AIMS: Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS). METHODS: Children (age 2-16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone...

BACKGROUND AND PURPOSE: Bardoxolone methyl (2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester, CDDO-Me) is a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which induces the expression of antioxidative-associated genes. CDDO-Me exerts protective effects against chronic inflammatory diseases in the kidneys and lungs. However, its pharmacological effects on metabolic dysfunction-associated steatohepatitis (MASH) caused by fat accumulation remain unknown...

OBJECTIVES: To determine the intention to use physical restraint (PR) and the relationship with sociodemographic and professional variables of the Paediatric Intensive Care Unit (PICU) nurses. RESEARCH METHODOLOGY/DESIGN AND SETTING: A multicentre and correlational study was carried out from October 2021 to December 2023 in five paediatric intensive care units from five maternal and child hospitals in Spain. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire was provided...

PURPOSE: Dysgeusia is a common side effect in oncology patients, significantly impacting their quality of life. This systematic review aims to evaluate the effectiveness of non-pharmacological strategies in treating dysgeusia in patients undergoing chemotherapy or radiotherapy. METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search across five databases: PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database...

AIMS: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. METHODS: A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022...

BACKGROUND AND PURPOSE: It is well acknowledged that tobacco-derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco-derived carcinogen nicotine-derived nitrosamine ketone (NNK)-treated A/J mice. EXPERIMENTAL APPROACH: RNA sequencing was used to detect the level of long non-coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR-328-3p in vitro, and NNK-treated A/J mice were used to test their function in vivo...

BACKGROUND AND PURPOSE: Excessive fibrogenesis is associated with adverse cardiac remodelling and heart failure. The myofibroblast, primarily derived from resident fibroblast, is the effector cell type in cardiac fibrosis. Megakaryocytic leukaemia 1 (MKL1) is considered the master regulator of fibroblast-myofibroblast transition (FMyT). The underlying transcriptional mechanism is not completely understood. Our goal was to identify novel transcriptional targets of MKL1 that might regulate FMyT and contribute to cardiac fibrosis...

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BACKGROUND AND PURPOSE: Acute graft-versus-host disease (GVHD) remains a major barrier to successful transplantation outcomes. Recent studies have shown that pharmacotherapy for GVHD should target both the innate and adaptive inflammatory immune responses. Juglone, a redox-active phytochemical found in walnuts, has shown potent anti-inflammatory effects in models of colitis and inflammatory bowel disease. However, its effects on T-cell-mediated immune responses remain largely unknown...

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP) is a potent vasodilator. While its signalling is assumed to be mediated via increases in cAMP, this study focused on elucidating the actual intracellular signalling pathways involved in CGRP-induced relaxation of human isolated coronary arteries (HCA). EXPERIMENTAL APPROACH: HCA were obtained from heart valve donors (27 M, 25 F, age 54 ± 2 years). Concentration-response curves to human α-CGRP or forskolin were constructed in HCA segments, incubated with different inhibitors of intracellular signalling pathways, and intracellular cAMP levels were measured with and without stimulation...

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021...

BACKGROUND AND PURPOSE: Neurotransmission and neuroinflammation are controlled by local increases in both extracellular ATP and the endocannabinoid 2-arachidonoyl glycerol (2-AG). While it is known that extracellular ATP stimulates 2-AG production in cells in culture, the dynamics and molecular mechanisms that underlie this response remain poorly understood. Detection of real-time changes in eCB levels with the genetically encoded sensor, GRABeCB2.0 , can address this shortfall. EXPERIMENTAL APPROACH: 2-AG and arachidonoylethanolamide (AEA) levels in Neuro2a (N2a) cells were measured by LC-MS, and GRABeCB2...

Hospital-associated venous thromboembolism (VTE) is defined as any case of VTE occurring during hospital admission and for up to 90 days post discharge. It accounts for over 50% of all cases of VTE internationally; indeed, there are an estimated 10 million cases of hospital-associated VTE annually. Over the last decade, there has been increasing interest in improving VTE risk assessment and thromboprophylaxis. This review summarises all the recent and ongoing major research studies and future challenges in the different areas, including medical, surgical and obstetric patients, as well as special areas such as lower limb immobilisation...