Utility of a whole blood single platelet counting assay to monitor the effects of tirofiban in patients with acute coronary syndromes scheduled for coronary intervention.

This study aimed to establish the utility of a whole-blood single-platelet counting (WBSPC) assay, a measure of microaggregation, in monitoring the effects of tirofiban, comparing this with optical aggregometry (OA) and the Ultegra TRAP cartridge system (UTC), measures of macroaggregation. Fifty-nine patients with acute coronary syndrome scheduled for coronary angiography +/- angioplasty were studied. WBSPC assay (ADP 0.

Biology and pharmacology of the platelet P2Y12 receptor.

Platelets possess two receptors for ADP, P2Y(1) and P2Y(12). ADP is released from platelet dense granules upon platelet activation by numerous agonists and thereby amplifies platelet responses regardless of the initial stimulus. The P2Y(1) receptor is one of many platelet receptors coupled to Gq and initiates ADP-induced activation.

Magnetic resonance imaging of myocardial infarction using a manganese-based contrast agent (EVP 1001-1): preliminary results in a dog model.

Purpose: To investigate the MRI characteristics of an intracellular manganese-based contrast agent, EVP 1001-1 (Eagle Vision Pharmaceutical Corp.), in a canine model of myocardial infarction.

Materials And Methods: Three dogs were imaged 14-37 days following permanent ligation of the left anterior descending coronary artery (LAD).

Catalase inhibition by amino triazole induces oxidative stress in goldfish brain.

The effects of in vivo inhibition of catalase by 3-amino 1,2,4-triazole (AMT) on the levels of damage products resulting from reactive oxygen species attack on proteins and lipids as well as on the activities of five antioxidant and associated enzymes were studied in the brain of goldfish, Carassius auratus. Intraperitoneal injection of AMT at a concentration of 0.1 mg/g wet weight caused a gradual decrease in brain catalase activity over 72 h, whereas higher AMT concentrations (0.

Spectrum of effects detected in the rat functional observational battery following oral administration of non-CNS targeted compounds.

Introduction: The Functional Observational Battery (FOB) is a systematic evaluation of nervous system function in the rat, comprising more than 30 parameters across autonomic, neuromuscular, sensorimotor and behavioural domains. We have collated FOB outcomes from 50 compounds that were not targeted at CNS disorders, and would therefore be anticipated to have relatively few CNS side-effects, for evaluation of the FOB as part of the safety pharmacology 'core battery'.

Methods: Male Han Wistar rats (200-300 g) were used, with n=6 per treatment group.

Supporting young people who repeatedly self-harm.

This paper explores the views and experiences of a group of 74 young people aged 16-22 who were interviewed following presentation in accident and emergency (A&E) departments after intentionally harming themselves. It focuses on a sub-group of 38 young people with a history of self-harm behaviour that extended from when they were under the age of 16, one-third of whom had been or were currently in care. Whilst some had kept their self-harming hidden and had not received any professional intervention until they reached adulthood, others had been in touch with services, although their treatment had not prevented them from continuing to self-harm.

Effect of free radical scavenger (tempol) on intrarenal oxygenation in hypertensive rats as evaluated by BOLD MRI.

Purpose: To demonstrate a differential response following administration of a free radical scavenger, tempol, in kidneys of hypertensive compared to normotensive rats.

Material And Methods: Data were obtained in spontaneously hypertensive rats (SHR, N = 5). Wistar-Kyoto rats (WKY, N = 6) were used as normotensive controls.

Potentiation of platelet aggregation by heparin in human whole blood is attenuated by P2Y12 and P2Y1 antagonists but not aspirin.

Introduction: Unfractionated heparin (UFH) potentiates platelet aggregation induced by some agonists. P2Y12 and P2Y1 receptors play a major role in amplifying platelet aggregation. We assessed the ability of cangrelor, a selective P2Y12 antagonist, A2P5P, a selective P2Y1 antagonist, and aspirin to block the potentiating effects of heparin.

Detection, integration and persistence of aeromonads in water distribution pipe biofilms.

The occurrence of Aeromonas spp. within biofilms formed on stainless steel (SS), unplasticized polyvinyl chloride (uPVC) and glass (GL) substrata was investigated in modified Robbins Devices (MRD) in potable (MRD-p) and recycled (MRD-r) water systems, a Biofilm Reactor (BR) and a laboratory-scale pipe loop (PL) receiving simulated recycled wastewater. No aeromonads were isolated from the MRD-p whereas 3-10% of SS and uPVC coupons (mean 3.

Effect of pregnancy and 5alpha-pregnan-3alpha-ol-20-one on atrial receptor afferent discharge in rats.

The atrial volume reflex is attenuated in pregnancy. This may be mimicked by chronic administration of 5alpha-pregnan-3alpha-ol-20-one (pregnan). We investigated whether afferent output from sensory receptors may be suppressed at this time.

Biofilms, thermophilic amoebae and Legionella pneumophila--a quantitative risk assessment for distributed water.

A simplistic quantitative microbial risk assessment (QMRA) based on the maximum risk curve (r = 1) was developed for Legionella within a water distribution system. Both biofilms and a thermophilic isolate of acanthamoebae were shown to increase the resistance of Legionella to conventional thermal disinfection by between one and two logs respectively. The level of risk presented to consumers was shown to exceed the USEPA 10(-4) benchmark in many cases tested.

Opposing FGF and retinoid pathways: a signalling switch that controls differentiation and patterning onset in the extending vertebrate body axis.

Construction of the trunk/caudal region of the vertebrate embryo involves a set of distinct molecules and processes whose relationships are just coming into focus. In addition to the subdivision of the embryo into head and trunk domains, this "caudalisation" process requires the establishment and maintenance of a stem zone. This sequentially generates caudal tissues over a long period which then undergo differentiation and patterning in the extending body axis.

1-Bromo-2,6-dihydroxybenzene containing R(4)(4)(8) rings and C(2) helices.

Molecules of the title compound (also known as 2-bromoresorcinol), C(6)H(5)BrO(2), are essentially planar and possess normal geometrical parameters. The crystal packing is influenced by O-H..

De novo gene expression and antisense inhibition in cultured cells of BmTRN-1, cloned from the midgut of the silkworm, Bombyx mori, which is homologous with mammalian TIA-1/R.

A cDNA encoding a 388 amino acid TIA-1-type RNA-binding protein (BmTRN-1) was isolated from midgut cDNAs of the silkworm, Bombyx mori, via homologous cloning, in order to characterize its function. The deduced amino acid sequence, most likely encoded by a single copy gene, has significant homology with human TIA-1 and TIAR known as apoptotic regulators and recently reported to function as important factors for either splicing or translation. RT-PCR analysis showed that the BmTRN-1 gene was vigorously transcribed in the midgut at the gut purge stage, indicating a possible relation to the tissue-decomposing process in larval-pupal metamorphosis.

Evaluation of Chromocult coliform agar for the detection and enumeration of Enterobacteriaceae from faecal samples from healthy subjects.

The purpose of this study was to examine the use of Chromocult agar medium for isolation and enumeration of Enterobacteriaceae from human faecal samples, to compare it to MacConkey agar and to evaluate its usefulness as a possible alternative selective medium in human faecal studies. The medium was shown to be effective in identifying Escherichia coli and coliforms in faeces without the need for extensive accompanying biochemical tests for confirmation of identity. A positive correlation (r=0.

Kidneys in hypertensive rats show reduced response to nitric oxide synthase inhibition as evaluated by BOLD MRI.

Purpose: To examine whether the noninvasive technique of blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) can detect changes in renal medullary oxygenation following administration of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). Hypertension is associated with endothelial dysfunction and is characterized by a lack of response to endothelial-dependent vasoactive substances, including nitric oxide synthase inhibitors. We hypothesized that the magnitude of the change would be reduced in the kidneys of hypertensive subjects relative to normal controls.

Correlation of characteristics of gel extrusion module (GEM) tablet formulation and drug dissolution rate.

The purpose of the study was to characterize the swelling properties of controlled release tablet formulations with compositional and processing differences. A correlation was also established between the drug dissolution rate from the controlled release gel extrusion module (GEM) tablet and the swelling properties of the core tablet. The GEM tablet consisted of a core tablet of water swellable Carbopol polymer, a neutralizing agent, drug, and excipients.

Freeze-induced expression of a novel gene, fr47, in the liver of the freeze-tolerant wood frog, Rana sylvatica.

The ability to endure the freezing of body fluids is well developed as an adaptation for winter survival in several species of woodland frogs. Recently, the mechanisms supporting natural freeze tolerance have been shown to include the expression of novel genes. One such novel gene, fr47, codes for a 390-amino acid protein present in the livers of freeze-tolerant anurans (Rana sylvatica, Pseudacris crucifer, Hyla versicolor) but not in freeze-intolerant species (Rana pipiens, Scaphiopus couchii).

Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease.

We compared the antiplatelet effects of clopidogrel and the intravenous platelet P2Y(12) receptor antagonist AR-C69931MX, which acts on the same receptor as clopidogrel by a different and reversible mechanism and, unlike clopidogrel, is active in vitro. Thirteen patients with acute coronary syndromes entered into a phase II study of intravenous AR-C69931MX (Group 1) and eight patients undergoing intracoronary stent implantation and treated with clopidogrel (Group 2) were studied using a whole blood single-platelet counting aggregation assay. Group 2 patients were also studied using turbidimetry with ADP and TRAP as agonists and whole blood [(14)C]5HT release to study dense granule secretion in response to ADP, collagen and TRAP.

Application of slurry bridging experiments at controlled water activities to predict the solid-state conversion between anhydrous and hydrated forms using theophylline as a model drug.

The role of water activity (a(w)), relative humidity (RH) and temperature on the hydration state of theophylline has been investigated. Slurry bridging experiments at controlled water activities, using powder X-ray diffraction (PXRD) and thermogravimetric analysis (TGA) to characterise the solid phase, established that the hydrate is the thermodynamically stable form of theophylline at a(w) > or = 0.5 at 4 degrees C, a(w) > or = 0.

Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin.

Platelet-leukocyte interactions are recognised to have pro-inflammatory effects, which may be important in the pathophysiology of ischaemic heart disease. Clopidogrel and the novel intravenous antithrombotic agent AR-C69931MX act at the level of the platelet P2Y12 receptor, which is known to amplify platelet activation, aggregation and other responses induced by numerous platelet agonists. We studied the effects of clopidogrel and aspirin on ADP-induced platelet-leukocyte conjugate formation and P-selectin expression in healthy volunteers.

Patterns of cognitive impairment in Alzheimer's disease: assessment and differential diagnosis.

In routine clinical practice, the diagnosis of Alzheimer's disease (AD) is commonly made according to NINCDS-ADRDA criteria. As pathological verification is typically not available, such a diagnosis remains probable rather than definite. A diagnosis of probable AD is nevertheless fairly accurate (0.

Modulation of sodium channels in primary afferent neurons.

Electrophysiological studies have revealed that the properties of voltage-gated Na+ channels can be modified by phosphorylation. Na+ channels have multiple sites for phosphorylation by protein kinases A and C (PKA and PKC). A change in the phosphorylation state of Na+ channels is an important mechanism of neuromodulation for both central and peripheral neurons.

Natural progression of Oesophagostomum bifurcum pathology and infection in a rural community of northern Ghana.

An estimated 250,000 people in northern Ghana and Togo are infected with the intestinal helminth parasite Oesophagostomum bifurcum, as detected by stool cultures. Clinical disease caused by O. bifurcum is responsible for about 50 cases per year at the region's central hospital, and presents as painful abdominal masses: inflammatory colonic nodules containing live juvenile stages of the helminth.

Regulation of oxygen sensing in peripheral arterial chemoreceptors.

The carotid bodies are a small pair of highly vascularized and well perfused organs located at each carotid artery bifurcation, strategically situated to sense oxygen in arterial blood as it leaves the heart. Carotid body glomus cells are identified as the primary oxygen sensors, which respond to changes in blood P(O(2)) within milliseconds. Acute hypoxia causes a rapid increase in carotid sinus nerve (CSN) activity, providing afferent signals to the respiratory center in the brainstem.