When calculating derivatives of structure factors, there is one particular term (the derivatives of the atomic form factors) that will always be zero in the case of tabulated spherical atomic form factors. What happens if the form factors are non-spherical? The assumption that this particular term is very close to zero is generally made in non-spherical refinements (for example, implementations of Hirshfeld atom refinement or transferable aspherical atom models), unless the form factors are refinable parameters (for example multipole modelling). To evaluate this general approximation for one specific method, a numerical differentiation was implemented within the NoSpherA2 framework to calculate the derivatives of the structure factors in a Hirshfeld atom refinement directly as accurately as possible, thus bypassing the approximation altogether.
View Article and Find Full Text PDFThe relationship between the structure and the properties of a drug or material is a key concept of chemistry. Knowledge of the three-dimensional structure is considered to be of such importance that almost every report of a new chemical compound is accompanied by an X-ray crystal structure - at least since the 1970s when diffraction equipment became widely available. Crystallographic software of that time was restricted to very limited computing power, and therefore drastic simplifications had to be made.
View Article and Find Full Text PDFObjectives: To examine whether young peoples' risk of cannabis, mephedrone and novel psychoactive substances (NPS) use is associated with school substance-misuse policy.
Design: A cross-sectional survey of secondary school students combined with a School Environment Questionnaire and independently coded school substance-misuse policies (2015/6).
Setting: 66 secondary schools in Wales.
Background: Existing guidance for developing public health interventions does not provide information for researchers about how to work with intervention providers to co-produce and prototype the content and delivery of new interventions prior to evaluation. The ASSIST + Frank study aimed to adapt an existing effective peer-led smoking prevention intervention (ASSIST), integrating new content from the UK drug education resource Talk to Frank ( www.talktofrank.
View Article and Find Full Text PDFBackground: Most patients with chest pain have nothing wrong with their cardiac function. Psychological forms of treatment for this condition are more likely to be successful than others.
Methods/design: A two-arm parallel controlled randomized trial of standard care versus a modified form of cognitive behaviour therapy for chest pain (CBT-CP) in patients who have attended emergency hospital services.
Safety and efficacy of alemtuzumab in the treatment of AR in children after renal transplantation is unknown. Five episodes of refractory late AR in three children (three episodes in patient 1 and a single episode in patients 2 and 3 occurring after 7-23 months of transplantation) were treated with one dose of alemtuzumab as a rescue therapy. Four episodes (Banff IA-IB) in patients 1 and 2 reversed fully or partially with alemtuzumab, whereas patient 3 with Banff IB-IIA AR failed to respond.
View Article and Find Full Text PDFSerum uric acid (UA) is positively associated with hypertension (HTN). HTN is common in pediatric patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We assessed the relationship between UA and BP in 63 pediatric dialysis patients by measuring pre-treatment UA levels and BP in HD patients and in-center UA levels and blood pressure (BP) in PD patients.
View Article and Find Full Text PDFStatins (HMG-CoA reductase inhibitors) exhibit beneficial effects on the vasculature independently of their cholesterol-lowering properties. These pleiotropic effects underlie the ability of statins to reduce intimal hyperplasia in saphenous vein (SV) bypass grafts by attenuating smooth muscle cell (SMC) invasion and proliferation. Although all statins can effectively lower cholesterol, the pleiotropic effects of individual statins may well differ.
View Article and Find Full Text PDFStatins can reduce adverse myocardial remodeling independently of their cholesterol-lowering ability. We have previously reported that simvastatin inhibits tumor necrosis factor-alpha (TNFalpha)-induced cardiac myofibroblast invasion and MMP-9 secretion, key events in this remodeling process. The aim of the present study was to investigate the mechanisms underlying this effect.
View Article and Find Full Text PDFAntisense Nucleic Acid Drug Dev
October 1997
The subchronic toxicity of ISIS 2302 and ISIS 3082, phosphorothioate oligonucleotides with antisense activity against human and murine ICAM-1 mRNA, respectively, was investigated in CD-1 mice. ISIS 2302 is currently in clinical trials as an anti-inflammatory agent. Because of the differences in mRNA sequence targets between humans and mice, ISIS 2302 has no pharmacologic activity in mice.
View Article and Find Full Text PDFAlthough phencyclidine (PCP) has several neurochemical effects, the most pharmacologically relevant are thought to be its ability to antagonize the activity of N-methyl-D-aspartate (NMDA)-type glutamate receptors and to increase extracellular dopamine concentrations. In order to elucidate the nature and consequence of PCP actions on glutamatergic and dopaminergic pathways, this study examined the response of extrapyramidal and limbic neurotensin systems to this drug. Multiple, but not single, doses of PCP caused increases in striatal neurotensin-like immunoreactivity content of 150-200% of control.
View Article and Find Full Text PDFIn this study we evaluated the effects of multiple administrations of selective dopamine D1 and D2 receptor agonists and antagonists on striatal, nigral, accumbens, pallidal and cortical neuropeptide Y systems. Treatment with the D1 receptor agonist, SKF 38393, decreased, while that with the D1 receptor antagonist, SCH 23390, increased neuropeptide Y-like immunoreactivity in the globus pallidus and several regions within the caudate-putamen. SCH 23390 did not change accumbens neuropeptide Y-like immunoreactivity levels but SKF 38393 increased neuropeptide Y-like immunoreactivity levels in anterior and decreased neuropeptide Y-like immunoreactivity levels in the posterior nucleus accumbens.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
November 1993
Neuropeptide Y-like immunoreactivity (NPYLI) in the frontal cortex and nucleus accumbens was significantly decreased after acute and multiple administrations of phencyclidine-HCl (PCP). The role of dopamine, serotonin and sigma receptors in these PCP-induced effects was evaluated. Neither the dopamine D1 antagonist SCH 23390 nor the D2 antagonist sulpiride by itself altered cortical neuropeptide systems, but in combination they totally blocked the PCP-induced changes.
View Article and Find Full Text PDFMultiple administrations of the psychotomimetic drug, phencyclidine-HCI (PCP), decreased striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels in a dose-dependent manner. Single or multiple PCP administrations decreased striatal NPY levels after 10-12 h; levels returned to control 24 h after a single dose or 58 h after multiple doses. In contrast, no significant changes were seen in nigral NPY levels with either acute or multiple-dose PCP treatments.
View Article and Find Full Text PDFThe N-methyl-D-aspartate (NMDA)-type glutamate receptor was shown to mediate dopamine-induced dynorphin A (Dyn) changes in extrapyramidal and limbic structures. MK801, a potent noncompetitive antagonist of the NMDA receptor, blocked increases in striatal and nigral Dyn content following single and multiple administrations of methamphetamine (METH). Significant attenuation of the METH-induced increases occurred with MK801 doses of 0.
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