Universities as Partners in Primary Health Care Innovation.

Universities have a unique role in the health ecosystem as providers of trained staff and discoverers of health innovations. However, often they sit in silos waiting for their rare blockbuster discoveries to change clinical care or seeing health services simply as future employers of their graduates or clinical trial sites. It is a transactional and targetted relationship.

[Exceptional pacemaker complication in Still's disease].

Case Report: A 49-year-old man with Still's disease presented with a rash above his pacemaker scar. In 2012, there was a replacement of the generator in which the position was changed from subpectoral to subcutaneous. A revision operation was performed after the local finding became worse, turning from a granuloma to a macula.

Elevated plasma prostaglandins and acetylated histone in monocytes in Type 1 diabetes patients.

Aims/hypothesis: Inflammation is implicated in diabetes and cyclooxygenase (COX) is involved in vascular inflammatory processes, participating in both atherosclerosis and thrombosis. The aims were to determine whether levels of monocyte COX and plasma COX metabolites are increased in Type 1 diabetic patients and to determine whether these could be linked to histone hyperacetylation.

Materials And Methods: Monocytes from 19 Type 1 diabetic and 39 non-diabetic control subjects were probed for COX and acetylated histone H4 proteins by immunoblotting.

Endothelial nitric oxide attenuates Na+/Ca2+ exchanger-mediated vasoconstriction in rat aorta.

Background And Purpose: The Na+/Ca2+ exchanger (NCX) may be an important modulator of Ca2+ entry and exit. The present study investigated whether NCX was affected by prostacyclin and nitric oxide (NO) released from the vascular endothelium, as NCX contains phosphorylation sites for PKA and PKG.

Experimental Approach: Rat aortic rings were set up in organ baths.

The time course of plausibility effects on eye movements in reading: evidence from noun-noun compounds.

Readers' eye movements were monitored as they read sentences containing noun-noun compounds that varied in frequency (e.g., elevator mechanic, mountain lion).

A role for cyclooxygenase in aging-related changes of beta-adrenoceptor-mediated relaxation in rat aortas.

beta-Adrenoceptor-mediated vasorelaxation decreases with age in various vascular beds. The present study investigated the roles of cyclooxygenase (COX) on beta-adrenoceptor vasorelaxation by isoprenaline in 8- and 54-week-old rat aortas. The vasorelaxation responses by isoprenaline (0.

Endogenous nitric oxide attenuates beta-adrenoceptor-mediated relaxation in rat aorta.

1. Divergent evidence suggests that the intracellular signalling pathways for beta-adrenoceptor-mediated vascular relaxation involves either cAMP/protein kinase (PK) A or endothelial nitric oxide (NO) release and subsequent activation of cGMP/PKG. The present study identifies the relative roles of NO and cAMP, as well as dependence on the endothelium for beta-adrenoceptor-mediated relaxation of rat isolated aortas.

Age-related changes in monocyte and platelet cyclooxygenase expression in healthy male humans and rats.

Cyclooxygenase (COX) catalyses the formation of prostanoids that are crucial in maintaining hemostasis and important in inflammation. Animal studies reveal that COX-1 and COX-2 expression increase in some cell types during aging. This study determined age-related changes in COX expression in platelets and monocytes.

Semantic evaluation of syntactic structure: evidence from eye movements.

An eye movement study of temporarily ambiguous closure sentences confirmed that the early closure penalty in a sentence like While John hunted the frightened deer escaped is larger for a simple past verb (hunted) than for a past progressive verb (was hunting). The results can be explained by the observation that simple past tense verbs convey an external viewpoint on an event, which presumably fits best when the event described has an endpoint. A definite description object supplies an endpoint.

Phorbol ester-induced contractility and Ca2+ influx in human cultured prostatic stromal cells.

In this study, we investigated the effects of protein kinase C (PKC)-activating phorbol esters upon Ca(2+) influx and contractility in human cultured prostatic stromal cells. Tissue obtained from patients undergoing transurethral resection of the prostate was used to generate explant cultures of prostatic stromal cells. These cells expressed detectable levels of PKCalpha, delta, gamma, lambda, and zeta, but not epsilon, iota, mu, or theta; isoforms and responded to both phorbol 12,13-diacetate (PDA) and 12-deoxyphorbol 13-tetradecanoate (DPT) with concentration-dependent contractions (pEC50+/-SEM 7.

Testosterone- and phorbol ester-stimulated proliferation in human cultured prostatic stromal cells.

Prostatic stromal proliferation may be commonly associated with the development of benign prostatic hyperplasia. In this study, we investigate the role of testosterone and protein kinase C in stimulating cultured stromal cell proliferation. Testosterone increased the uptake of [(3)H]-thymidine into the human cultured prostatic stromal cells, this was reduced by the protein kinase C inhibitors, bisindolylymaleimide (10 nM) and myristoylated protein kinase C inhibitor (mPKCi, 20 microM), but not by Gö 6983 (1 microM) or Gö 6976 (1 microM).

Gender differences in protein kinase G-mediated vasorelaxation of rat aorta.

Although gender and oestrogen treatment influence production of the vasorelaxant, NO, their influence on factors downstream in the NO signal-transduction pathway, specifically protein kinase G (PKG), remains unknown. We aimed to study the influence of sex hormones on PKG, along with the endothelial modulation of these effects, in rat thoracic aortic rings in two separate groups, control male and female rats and ovariectomized female rats after treatment with oestrogen or vehicle. Vessel preparations were preconstricted with phenylephrine (0.

The role of cyclic nucleotides and calcium in the relaxation produced by amrinone in rat aorta.

(1) The vasorelaxation produced by the phosphodiesterase 3 (PDE3) inhibitor, amrinone was investigated in isolated rat aorta denuded of endothelium. In the presence of extracellular Ca(2+), amrinone, milrinone and 3-isobutyl-1-methylxanthine (IBMX), relaxed endothelium-denuded rat aortic rings constricted with phenylephrine. While the actions of milrinone and IBMX were inhibited by the protein kinase G (PKG) inhibitor, Rp-8-Bromo guanosine-3',5' monophosphothioate (Rp-8-Br-cGMPS; 0.

Effects of oral combined hormone replacement therapy on platelet aggregation in postmenopausal women.

The effects of combined oestrogen/progestin hormone replacement therapy (HRT) on platelet aggregation were studied using women on HRT or placebo. The study involved 32 postmenopausal women (aged 50-75 years) who were enrolled in a double-blind randomized controlled trial, and who received either oral continuous combined HRT (Kliogest(R); 2 mg of oestradiol+1 mg of norethisterone) or placebo for a minimum of 6 months. Platelet aggregation was measured by whole-blood impedance aggregometry in response to the agonists collagen, arachidonic acid and ADP.

Differential abilities of phorbol esters in inducing protein kinase C (PKC) down-regulation in noradrenergic neurones.

1. The ability of several phorbol ester protein kinase C (PKC) activators (phorbol 12, 13-dibutyrate, PDB; phorbol 12, 13-diacetate, PDA; and 12-deoxyphorbol 13-acetate, dPA) to down-regulate PKC was studied by assessing their effects on electrical stimulation-induced (S-I) noradrenaline release from rat brain cortical slices and phosphorylation of the PKC neural substrate B-50 in rat cortical synaptosomal membranes. 2.

Amrinone reduces ischaemia-reperfusion injury in rat heart.

We investigated the effects of amrinone on ischaemia-induced changes in myocardial function in isolated rat hearts. Isolated hearts from male Sprague-Dawley rats (150-275 g) were perfused with physiological salt solution at a constant flow rate. The effects of amrinone (30 microM) on left ventricular end diastolic pressure, positive and negative dP/dt, heart rate and coronary perfusion pressure were observed following global ischaemia and reperfusion.

No involvement of nicotinic receptors in the facilitation of acetylcholine outflow in mouse cortex in the presence of neostigmine and atropine.

The role of nicotinic and muscarinic receptors in the modulation of acetylcholine release was studied using field stimulated mouse cortex slices incubated with [(3)H]-choline. Both acetylcholine (100 microM) and the cholinesterase inhibitor neostigmine (100 microM) inhibited the stimulation-induced (S-I) outflow of radioactivity but in the presence of atropine (0.3 microM) an enhancement was seen, which may be indicative of facilitatory nicotinic receptors.

Modulation of acetylcholine release from mouse cortex by protein kinase C: dependence on stimulation intensity.

Activation of protein kinase C (PKC) results in enhanced action-potential evoked release of a variety of transmitters. However, previous studies have suggested that acetylcholine release is poorly modulated by PKC compared to other transmitter types. We investigated the effect of stimulation conditions on PKC modulation of electrical stimulation-induced acetylcholine release in mouse cortex, which were incubated with [3H]choline.

M(2)/M(4)-muscarinic receptors mediate automodulation of acetylcholine outflow from mouse cortex.

Acetylcholine outflow can be modulated through inhibitory presynaptic muscarinic autoreceptors. This study was to identify which subtype is involved in mouse cortex. Five muscarinic antagonists and their ability to elevate stimulation-induced (S-I) acetylcholine outflow were tested in the presence of neostigmine, which decreased S-I outflow.

Age-related involvement of the endothelium in beta-adrenoceptor-mediated relaxation of rat aorta.

The signalling pathway involved in beta-adrenoceptor relaxation was studied in aortas from rats either 8 or 54 weeks of age. The vasorelaxation produced by isoprenaline was almost completely abolished by endothelium removal in 54-week aortas, whereas in 8-week aortas, the effect was much smaller. The nitric oxide synthase inhibitor N-methyl-1-arginine acetate (L-NMMA) partially attenuated the isoprenaline induced relaxation to a similar extent in both age groups when the endothelium was intact, suggesting that although nitric oxide was involved, it could not explain the age-related difference.

Structural determinants of phorbol ester binding in synaptosomes: pharmacokinetics and pharmacodynamics.

The present study used structurally distinct phorbol esters to investigate the relationship between their pharmacokinetics of binding to protein kinase C (PKC) in rat brain cortex synaptosomes, their affinity for PKC in synaptosomes and ability to enhance noradrenaline release from rat brain cortex. Affinity binding studies using [3deoxyphorbol 13-tetradecanoate (dPT)=PDB&z. Gt;12-deoxyphorbol 13-acetate (dPA)=phorbol 12,13-diacetate (PDA).

The structural requirements for phorbol esters to enhance serotonin and acetylcholine release from rat brain cortex.

The effects of various phorbol-based protein kinase C (PKC) activators on the electrical stimulation-induced (S-I) release of serotonin and acetylcholine was studied in rat brain cortical slices pre-incubated with [3H]-serotonin or [3H]-choline to investigate possible structure-activity relationships. 4beta-phorbol 12,13-dibutyrate (4betaPDB, 0.1-3.

Endothelium removal induces iNOS in rat aorta in organ culture, leading to tissue damage.

After endothelial damage in vivo, there is an induction of nitric oxide synthase (NOS) in the underlying smooth muscle cells. We hypothesized that intrinsic factors could induce NOS independently of blood elements. This was tested using an in vitro organ culture technique.

Protein kinase C: a physiological mediator of enhanced transmitter output.

Protein kinase C (PKC), activated by either diacylglycerol and/or arachidonic acid, through the activation of presynaptic receptors or nerve or nerve depolarization is involved is involved in the enhancement of transmitter release from many neural types. This facilities is most likely mediated by the phosphorylation of proteins involved in vesicle dynamics although a role for ion channels cannot be ruled out. PKC is not fundamental to the release process but rather has a modulatory role of PKC is to help maintain transmitter output during prolonged or elevated levels of activation and this seems to parallel suggestions that PKC is involved in the movement of reserve pools of vesicles into release-study sites.