Lancet
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Up to 40% of patients with rheumatoid arthritis treated with anti-tumour necrosis factor (TNF) drugs do not respond because of primary inefficacy or loss of response. Although one explanation is that immunogenicity leads to the development of anti-drug antibodies and low drug concentrations, the clinical usefulness of pharmacological monitoring is debated. Our aim was to assess whether the presence of anti-drug antibodies and non-trough drug concentrations could predict treatment response in patients with rheumatoid arthritis treated with anti-TNF drugs. ⋯ MJ is a MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the UK Medical Research Council (grant number G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca, and the Medical Evaluation Unit. Arthritis Research UK (grant ref 20385).
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Worldwide, obesity has doubled since 1980. WHO declares obesity as preventable and attributes the increase in prevalence to high consumption of energy-rich foods and decreased physical activity. Epidemiological and experimental studies suggest that parents' and grandparents' diet could also have a role. We established a model of grandparents' high-fat diet (HFD) to explore potential mechanisms. ⋯ UK Medical Research Council.
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Patients with loss-of-function mutation in neurokinin B (NKB) and its receptor show hypogonadotropic hypogonadism characterised by failure to progress through puberty, indicating the involvement of this newly described hypothalamic peptide in human reproduction. However the role of NKB in regulating ovarian function in adult women is unknown. We tested the hypothesis that a NKB antagonist would decrease gonadotropin secretion and inhibit folliculogenesis in healthy women. ⋯ Wellcome Trust through the Scottish Translational and Therapeutics Initiative.
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Epilepsy is characterised by disturbed neuronal activity in the brain rendering it more susceptible to seizures. An understanding of the molecular mechanisms by which the balance between excitability and inhibition in neuronal networks is controlled will help to devise better treatment options. Hyperpolarising synaptic inhibition through GABAA (γ aminobutyric acid type A) and glycine receptors depends on the presence of the neuronal cation-chloride-cotransporter protein, KCC2. Several transcriptional and post-transcriptional mechanisms have been shown to regulate KCC2 and thereby affect the polarity and efficacy of inhibitory synaptic transmission. However, it is unknown whether regulation of KCC2 enables the transporter to attain different levels of activity, thus allowing a neuron to modulate the strength of inhibitory synaptic transmission to its changing requirements. We therefore investigated whether phosphorylation can allow KCC2 to achieve distinct levels of intracellular chloride ion concentrations in neurons. ⋯ Royal Society.
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The benefit of statins in the prevention of cardiovascular disease is well founded, derived from their lipid lowering and pleiotropic effects. The concept of lipoproteins as lipid transporters has evolved to encompass functions in coagulation, inflammation, and redox reactions due to their unique protein cargo. The aim of this study was to determine the effect of statin therapy on lipoproteins and their protein cargo by use of an unbiased bottom-up proteomics approach in people with hypercholesterolaemia. ⋯ British Heart Foundation.