Paul Carter

Activation of glycoprotein VI (GPVI) and C-type lectin-like receptor-2 (CLEC-2) underlies platelet activation by diesel exhaust particles and other charged/hydrophobic ligands

Platelets are activated by a range of stimuli that share little or no resemblance in structure to each other or to recognized ligands, including diesel exhaust particles (DEP), small peptides [4N1-1, Champs (computed helical anti-membrane proteins), LSARLAF (Leu-Ser-Ala-Arg-Leu-Ala-Phe)], proteins (histones) and large polysaccharides (fucoidan, dextran sulfate). This miscellaneous group stimulate aggregation of human and mouse platelets through the glycoprotein VI (GPVI)-FcR γ-chain complex and/or C-type lectin-like receptor-2 (CLEC-2) as shown using platelets from mice deficient in either or both of these receptors. In addition, all of these ligands stimulate tyrosine phosphorylation in GPVI/CLEC-2-double-deficient platelets, indicating that they bind to additional surface receptors, although only in the case of dextran sulfate does this lead to activation. DEP, fucoidan and dextran sulfate, but not the other agonists, activate GPVI and CLEC-2xa0in transfected cell lines as shown using a sensitive reporter assay confirming a direct interaction with the two receptors. We conclude that this miscellaneous group of ligands bind to multiple proteins on the cell surface including GPVI and/or CLEC-2, inducing activation. These results have pathophysiological significance in a variety of conditions that involve exposure to activating charged/hydrophobic agents.

Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation

The carotid body has been proposed to be an acute sensor of hypoglycaemia, although conflicting data exist regarding the ability of hypoglycaemia to stimulate the carotid body directly. The reason for these discrepancies is not known. In an in vitro, freshly isolated, intact rat carotid body preparation, chemoafferent function was unaffected and protected against metabolic injury for 30 min exposure to glucose deprivation. Glycogen granules and glycogen conversion enzymes were identified in type I cells and targeting of glycogenolysis or functional glycogen depletion both caused a more rapid run‐down of glycolysis during glucose deprivation. This shows that glycogen maintains carotid body sensory neuronal output in periods of restricted glucose delivery to protect the metabolic integrity of the organ during hypoglycaemia. The preservation of energetic status may account for the variation in the reported capacity of the carotid body to sense physiological glucose concentrations.

Fluorocyclohexanes. Part XVI. The six H-trifluoromethyldecafluoro- and two of the 2H,4H-trifluoromethylnonafluoro-cyclohexanes

Abstract Fluorination of benzotrifluoride by cobaltic fluoride at 260–280° gave, besides the fluorocarbon, the six possible tridecafluoromethylcyclohexane isomers, and two 2H,4H-dodecafluorides. Of the C 7 HF 13 compounds, only the cis−2H-, and the cis- and trans-4H-isomers could be isolated pure. The two 3H-isomers were made by pyrolysis of perfluoro(1-methyl-3-isopropylcyclohexane) in the presence of toluene. The trans-2H-isomer was made by further fluorination of one of the 2H,4H-dodecafluorides. Aqueous potash and the cis-2H-tridecafluoride gave 1-trifluoromethylnonafluorocyclohex-1-ene, which with stronger alkali hydrolysed to 1-carboxynonafluorocyclohex-1-ene. The cis- and trans- 2H and 4H-tridecafluorides were dehydrofluorinated by sodium fluoride at 320–380° (the cis-isomer of each pair reacted faster than the trans- : axial versus equatorial hydrogen) to give, respectively, the 1-trifluoromethylnonafluoro-ene and the 4-trifluoromethyl-isomer. The latter was isomerised to the former by sodium fluoride at 500–600°. The 1−CF 3 -ene gave hexafluoroglutaric acid on oxidation with alkaline potassium permanganate.

Length of hospital stay is shorter in South Asian patients with ischaemic stroke.

Publisher Rights Statement: NOTICE: this is the author’s version of a work that was accepted for publication in International Journal of Cardiology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in International Journal of Cardiology, Vol 187, May 2015, DOI: 10.1016/j.ijcard.2015.03.290

The impact of psychiatric comorbidities on the length of hospital stay in patients with heart failure.

BACKGROUNDnHeart failure (HF) is a major healthcare problem contributing significantly to hospital admission stays and National Health Service (NHS) spending. Reducing length of hospital stay (LoS) in HF is paramount in reducing this burden and is influenced by factors relating to the condition, sociodemographics and comorbidities. Psychiatric comorbidities are being increasingly identified amongst HF patients but their impact on LoS has not been studied in the UK.nnnMETHODSnWe investigated the impact of psychiatric comorbidities on LoS amongst 31,760 HF patients admitted to hospitals in North England between 1st January 2000 and 31st March 2013 from the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) study. The ACALM protocol uses ICD-10 and OPCS-4 coding to trace HF patients, psychiatric comorbidities and demographics including LoS.nnnRESULTSnAmongst 31,760 HF patients mean LoS in the absence of psychiatric comorbidities was 11.2days. The presence of a psychiatric comorbidity increased LoS by 3.3days. Logistic regression accounting for age, gender and ethnicity showed that LoS was significantly longer in patients suffering from depression (3.4days, p<0.001), bipolar disorder (8.8days, p<0.001) and all types of dementia (4.2days, p<0.001).nnnCONCLUSIONSnOur results demonstrate that psychiatric comorbidities have a significant and clinically important impact on LoS in HF patients in the UK. Clinicians should be actively aware of psychiatric conditions amongst HF patients and manage them to reduce LoS and ultimately the risk for patients and financial burden for the NHS.

Polyfluorocycloalkenes. Part XVI [1]. Some addition reactions of 1-trifluoromethylnonafluorocyclohex-1-ene

Abstract Reactions with alcohols and base replaced the vinylic fluorine of 1-trifluoromethylnonafluorocyclohex-1-ene(I) by methoxy and ethoxy groups. Fluorination with cobaltic fluoride gave, from the former, a number of saturated polyfluoro-ethers. Oxidation of the alkoxy-cycloalkenes gave hexafluoroglutaric acid. Cycloalkene I gave which ammonia an imino-enamine, which was hydrolysed by dilute acid to a keto-enamine. I was defluorinated by heated iron to octafluorotoluene.

The role of angioplasty in octogenarian patients with Acute Coronary Syndrome.

a ACALM Study Unit in collaboration with Aston Medical School, School of Medical Sciences, Aston University, Birmingham, UK b Birmingham Medical School, Birmingham, UK c Royal Free London NHS Trust, London, UK d Department of Cardiology, Manchester Royal Infirmary, Manchester, UK e Division of Cardiology, University of Birmingham, Birmingham, UK f School of Medicine, Cardiff University, Cardiff, UK g Division of Cardiovascular and Diabetes Research, University of Leeds, Leeds, UK h Department of Acute Medicine, North Western Deanery, Manchester, UK

93 Married patients with modifiable cardiovascular risk factors have lower mortality rates

Background Ischaemic heart disease (IHD) is the leading cause of mortality worldwide. Although modifiable cardiovascular risk factors, such as hypertension, diabetes and hyperlipidaemia, account for a large proportion of IHD the extent to which they are controlled is variable. The reasons for this undermanagement of risk factors is multifactorial and sociodemographic factors, such as marital status, could play an important role. This is especially important in light of recent evidence of higher mortality rates in single patients following acute coronary syndrome. However, more research is required into the impact of marital status on mortality in patients with cardiovascular risk factors. Objectives We aimed to investigate the impact of marital status on mortality of a large database of patients admitted with hypertension, hyperlipidaemia and type 2 diabetes. Methods Anonymous information on patients with hypertension, hyperlipidaemia and type 2 diabetes was obtained from hospitals in North England between 1stJanuary 2000 and 31stMarch 2013. This data was analysed according to the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) study protocol. ICD-10 and OPCS-4 codes were used to trace patients and demographics including marital status, comorbidities and mortality data. Mortality of patients of different marital statuses were compared by cox regression adjusted for age, gender, ethnicity and the top 10 contributors to mortality in the UK. P values<0.05u2009were taken as statistically significant. Results Amongst 9u200929u2009552 adult patients admitted during the study period there were 1u200968u2009431 patients with hypertension, 53u2009055 with hyperlipidaemia and 68u2009098 patients with type 2 diabetes. Crude mortality was highest among widowed patients in all 3 conditions. Logistic regression accounting for age, gender, ethnicity and the top contributors to mortality in the UK showed that married people, as compared to single people, with hypertension (OR 0.900), hyperlipidaemia (OR 0.836) and type 2 diabetes (OR 0.860) had significantly lower mortality rates. Adjusted mortality rates were also lower in widowed patients with hypertension (OR 0.973) and in both widowed and separated patients with type 2 diabetes (OR 0.965 and 0.974, respectively). Conversely, unmarried patients had significantly raised adjusted mortality rates in type diabetes (OR 1.046) and in hypertension (1.034). Conclusion Single patients with modifiable risk factors have significantly higher mortality rates compared to married patients which could help to explain the raised mortality rates documented in single patients following an acute coronary syndrome. Protective effects of marriage likely result from increased social support leading to healthier lifestyles and increased medication compliance. Our findings suggest a need for increased social support for single patients with modifiable cardiovascular risk factors.Abstract 93 Table 1