Promoting C–C Bond Coupling of Benzyne and Methyl Ligands in Electron-Deficient (triphos)Pt–CH 3 + Complexes

In situ generated benzyne reacts at room temperature with (triphos)Pt-CH3 (+) to form a five-coordinate π-complex (2) that is isolable and stable in solution. Thermolysis of 2 at 60 °C generates (triphos)Pt(o-tolyl)(+) (3), which is the product of formal migratory insertion of CH3 (-) onto the coordinated benzyne. The reaction of 2 with the acid Ph2NH2 (+) yields toluene at room temperature over the course of 8 h, while the same reaction with 3 only proceeds to 40% conversion over 2 days. These data indicate that the protonolysis of 2 does not proceed by CH3 migration onto benzyne to form 3 followed by protodemetalation. Instead, the data suggest either that protonation of 2 is first and is followed by H migration to yield a Pt(IV)Ph(Me) dication or that this latter species is generated by direct protonolysis of coordinated benzyne prior to reductive elimination of toluene

Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation

Rationale. Pharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation. Objectives. Here, we aimed to determine the functional involvement of dopamine D1 receptors in cued fear memory destabilisation, using systemic drug administration. Results. We observed that direct D1 receptor agonism was not sufficient to stimulate tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Instead, administration of the nootropic nefiracetam did facilitate mifepristone-induced amnesia, in a manner that was dependent upon dopamine D1 receptor activation, although. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters. Conclusions. The use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

A review of the positive and negative effects of cardiovascular drugs on sexual function: a proposed table for use in clinical practice

Several antihypertensive drugs, such as diuretics and β-blockers, can negatively affect sexual function, leading to diminished quality of life and often to noncompliance with the therapy. Other drug classes, however, such as angiotensin II receptor blockers (ARBs) are able to improve patients’ sexual function. Sufficient knowledge about the effects of these widely used antihypertensive drugs will make it possible for cardiologists and general practitioners to spare and even improve patients’ sexual health by switching to different classes of cardiac medication. Nevertheless, previous data (part I) indicate that most cardiologists lack knowledge about the effects cardiovascular agents can have on sexual function and will thus not be able to provide the necessary holistic patient care with regard to prescribing these drugs. To be able to improve healthcare on this point, we aimed to provide a practical overview, for use by cardiologists as well as other healthcare professionals, dealing with sexual dysfunction in their clinical practices. Therefore, a systematic review of the literature was performed. The eight most widely used classes of antihypertensive drugs have been categorised in a clear table, marking whether they have a positive, negative or no effect on sexual function

Promoting C–C Bond Coupling of Benzyne and Methyl Ligands in Electron-Deficient (triphos)Pt–CH₃⁺ Complexes

In situ generated benzyne reacts at room temperature with (triphos)­Pt–CH₃⁺ to form a five-coordinate π-complex (<b>2</b>) that is isolable and stable in solution. Thermolysis of <b>2</b> at 60 °C generates (triphos)­Pt­(o-tolyl)⁺ (<b>3</b>), which is the product of formal migratory insertion of CH₃^– onto the coordinated benzyne. The reaction of <b>2</b> with the acid Ph₂NH₂⁺ yields toluene at room temperature over the course of 8 h, while the same reaction with <b>3</b> only proceeds to 40% conversion over 2 days. These data indicate that the protonolysis of <b>2</b> does not proceed by CH₃ migration onto benzyne to form <b>3</b> followed by protodemetalation. Instead, the data suggest either that protonation of <b>2</b> is first and is followed by H migration to yield a Pt^IVPh­(Me) dication or that this latter species is generated by direct protonolysis of coordinated benzyne prior to reductive elimination of toluene

Experimental investigation of turbine stator well rim seal, reingestion and interstage seal flows using gas concentration techniques and displacement measurements

Gas turbine engine performance requires effective and reliable internal cooling over the duty cycle of the engine. Life predictions for rotating components subject to the main gas path temperatures are vital. This demands increased precision in the specification of the internal air system flows which provide turbine stator well cooling and sealing. This in turn requires detailed knowledge of the flow rates through rim seals and interstage labyrinth seals. Knowledge of seal movement and clearances at operating temperatures is of great importance when prescribing these flows. A test facility has been developed at the University of Sussex, incorporating a two stage turbine rated at 400 kW with an individual stage pressure ratio of 1.7:1. The mechanical design of the test facility allows internal cooling geometry to be rapidly re-configured, while cooling flow rates of between 0.71 CW, ENT and 1.46 CW, ENT, may be set to allow ingress or egress dominated cavity flows. The main annulus and cavity conditions correspond to in cavity rotational Reynolds numbers of 1.71 × 106 < Reϕ <1.93 × 106. Displacement sensors have been used to establish hot running seal clearances over a range of stator well flow conditions, allowing realistic flow rates to be calculated. Additionally, gas seeding techniques have been developed, where stator well and main annulus flow interactions are evaluated by measuring changes in gas concentration. Experiments have been performed which allow rim seal and re-ingestion flows to be quantified. It will be shown that this work develops the measurement of stator well cooling flows and provides data suitable for the validation of improved thermo-mechanical and CFD codes, beneficial to the engine design process