Metastin-like immunoreactivity in the rat medulla oblongata and spinal cord.

Metastin, the product of metastasis suppressor gene KiSS-1, is proposed to be the natural ligand for the G-protein-coupled receptor GPR54, known also as AXOR12. This immunohistochemical study, using a rabbit polyclonal antiserum against the human metastin fragment (45-54)-NH(2), showed that in rats metastin-like immunoreactivity (MTS-LI) was present in neurons of the nucleus of the solitary tract and caudoventrolateral reticular nucleus, and in cell processes of the spinal trigeminal tract and lateral reticular nucleus. MTS-LI was confined mainly to neurons and fibers at or caudal to the area postrema.

Quantitative neuropathological analysis of sudden infant death syndrome.

Detailed stereological analyses of specific regions of brains of children who had died from Sudden Infant Death Syndrome (SIDS) was undertaken to determine whether global evidence of an underlying pathology exists, contributing to an increased susceptibility to SIDS. A significant reduction in the total number of neocortical neurones and neurone volume was observed in SIDS normal birth weight (NBW) infants in comparison to controls. A significant reduction in both volume and total neurone number were also noted in the dorsal motor nucleus of the vagus in SIDS NBW group when compared with controls.

Eletriptan Pfizer.

Pfizer has developed and launched eletriptan, a 5-HT1B/1D agonist, for the potential treatment of migraine with and without aura. Eletriptan has 6-fold greater affinity for the 5-HT1D receptor than sumatriptan, and a 3-fold greater affinity for the 5-HT1B receptor [249570]. Eletriptan pharmacology has also been evaluated in vitro in comparison with zolmitriptan (AstraZeneca plc) and naratriptan (GlaxoSmithKline plc) [290116].

Cortical spreading depression in the feline brain following sustained and transient stimuli studied using diffusion-weighted imaging.

Cortical spreading depression (CSD) was induced by transient (10 min) applications of KCl in agar upon the cortical surface of alpha-chloralose anaesthetised cats. Its features were compared with CSD resulting from sustained applications of crystalline KCl through a mapping of the apparent diffusion coefficient (ADC) using diffusion-weighted echo planar imaging (DWI) over a poststimulus period of 60-100 min. Individual CSD events were computationally detected with the aid of Savitzky-Golay smoothing applied to critically sampled data derived from regions of interest (ROIs) made up of 2 x 2 pixel matrices.

Effects of oral raloxifene on serum estradiol levels and other markers of estrogenicity.

Objective: To determine the effects of raloxifene hydrochloride, 60 mg/d, on serum levels of E(2), estrone, sex steroid-binding globulin, thyroxine-binding globulin, and follicle-stimulating hormone (FSH) in postmenopausal women.

Design: Randomized placebo-controlled study at 16 centers in the United States.

Patient(s): Ninety three women 42 to 80 years of age who were at least 2 years postmenopausal.

The selective p38 inhibitor SB-239063 protects primary neurons from mild to moderate excitotoxic injury.

Inhibition of the p38 mitogen-activated protein kinase (MAP Kinase) pathway reduces acute ischemic injury in vivo, suggesting a direct role for this signaling pathway in a number of neurodegenerative processes. The present study was designed to evaluate further the role of p38 MAP Kinase in acute excitotoxic neuronal injury using the selective p38 inhibitor SB-239063 (trans-1-(4hydroxycyclohexyl)-4-(fluorophenyl)-5-(2-methoxy-pyrimidin-4-yl) imidazole). Unlike the widely used p38 inhibitor, SB-203580 (4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole), this second generation p38 inhibitor more selectively inhibits p38 MAP Kinase without affecting the activity of other MAP Kinase signaling pathways and provides a more accurate means to selectively assess the role of p38 in excitotoxicity that has not been previously possible.

Novel intercellular communication system in Escherichia coli that confers antibiotic resistance between physically separated populations.

Aims: To determine whether intercellular signalling can occur between physically separated populations of Escherichia coli.

Methods And Results: Intercellular signalling between physically discrete populations of E. coli BL21 was analysed in bi-partite Petri dishes.

Increased cortical expression of the orexin-1 receptor following permanent middle cerebral artery occlusion in the rat.

The orexins (hypocretins) have recently been implicated in neurodegeneration associated with narcolepsy. Therefore, the current study was designed to investigate changes in the expression of prepro-orexin and the orexin receptors, OX1R and OX2R following permanent middle cerebral artery occlusion (MCAO) in the rat. Six and twenty-four hours following MCAO, increased OX1R mRNA and protein expression (as assessed by Western blotting and immunohistochemistry) was detected in the ischaemic cortex compared with control tissue.

Expression of the complement C3a and C5a receptors after permanent focal ischemia: An alternative interpretation.

The receptors for the complement anaphylatoxins C3a and C5a are expressed by glial cells and neurons in normal and inflamed brain. Previous studies demonstrated modest elevations in mRNA expression of these receptors in a model of focal cerebral ischemia. Using a similar model system for both mice and rats, we report markedly different patterns of anaphylatoxin receptor mRNA expression in cerebral ischemia.

The behavioural effect of middle cerebral artery occlusion on apolipoprotein-E deficient mice.

The behavioural effects of middle cerebral artery occlusion (MCAO) in apolipoprotein-E deficient (Apo-E KO) mice were investigated using a modified SHIRPA protocol and compared with effects in wild type littermate controls. The MCA was permanently occluded by insertion of an intraluminal filament to its origin on the Circle of Willis and behavioural responses were observed 24 h later. MCAO treatment caused a range of changes in the wild type mice whereas, few differences were observed in the Apo-E KO mice in the behavioural observation.

Inhibition of factor IX(a) is protective in a rat model of thromboembolic stroke.

Background And Purpose: Although used clinically to prevent stroke, there are few examples of anticoagulant investigations in the treatment of acute thromboembolic stroke in animal models. The treatment of thromboembolic stroke in experimental models has been investigated almost exclusively around the use of tissue plasminogen activator (tPA). In this study, using a rat thromboembolic stroke model, we investigated the use of an inhibitory anti-factor IX(a) monoclonal antibody (SB 249417) for the treatment of thromboembolic stroke and compared its efficacy to that of tPA.

Antarctic climate cooling and terrestrial ecosystem response.

The average air temperature at the Earth's surface has increased by 0.06 degrees C per decade during the 20th century, and by 0.19 degrees C per decade from 1979 to 1998.

Programmable microchip monitoring of post-stroke pyrexia: effects of aspirin and paracetamol on temperature and infarct size in the rat.

Background: Recent studies have demonstrated spontaneous and prolonged hyperthermia following stroke in both humans and rodents. However, a full characterization of these pyretic changes and the effects of anti-pyretic drugs on outcome is not available.

Methods: The aims of this study were to monitor conscious body temperature (n=10 per group) using programmable microchips for up to 24 h in rats following either permanent (p) or 90 min transient (t) middle cerebral artery occlusion (MCAO) or sham surgery, and to evaluate the relationship to hypothalamic damage.

Assessment of white matter injury following prolonged focal cerebral ischaemia in the rat.

The ability of putative neuroprotective compounds to protect against white matter injury remains poorly investigated due to the lack of suitable methods for assessing white matter injury. This study was therefore designed to investigate the utility of Tau 1 (oligodendrocytes/axons), myelin basic protein (MBP; myelin) and amyloid precursor protein (APP; axons) immunohistochemistry in assessing white matter injury at various times following middle cerebral artery occlusion (MCAO) in the rat. Focal cerebral, ischaemia was induced in halothane-anaesthetised rats using an intraluminal thread model.

Intracellular drug delivery using low-frequency ultrasound: quantification of molecular uptake and cell viability.

Purpose: To determine the dependence on acoustic parameters of molecular uptake and viability of cells exposed to low-frequency ultrasound.

Methods: DU145 prostate cancer cells bathed in a solution of calcein were exposed to ultrasound at 24 kHz over a range of different acoustic pressures. exposure times, pulse lengths, and duty cycles.

Systematic genetic analysis with ordered arrays of yeast deletion mutants.

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes.

Diffusion-weighted MRI used to detect in vivo modulation of cortical spreading depression: comparison of sumatriptan and tonabersat.

Spreading cortical depolarization and depression of electroencephalographic activity (SD) may underlie the aura and spreading neurovascular events of migraine. Cortical depolarization may also precipitate the progressive development of cerebral pathology following ischemia. However, data on SD in the human brain are sparse, most likely reflecting the technical difficulties involved in performing such clinical studies.

Development of a neuronal pressure sensor.

Neuronal sensory systems are capable of performing very complex signal processing functions. Reconstruction of such sensory systems in vitro should enable whole-cell biological sensors to be generated that possess inherent signal processing capabilities. In this paper, the results of preliminary investigations to produce a mechanosensory neuronal network are presented.

Selective increases in cytokine expression in the rat brain in response to striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1.

A number of cytokines contribute to acute experimental neurodegeneration. The cytokine response can have detrimental or beneficial effects depending on the temporal profile and balance between pro- and anti-inflammatory molecules. Our recent data suggest that the pro-inflammatory cytokine interleukin-1beta (IL-1beta) acts at specific sites (e.

Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement.

Objectives: A panel of 14 physicians practicing medicine in the United States with expertise in radiology, obstetrics and gynecology, gynecologic oncology, hysteroscopy, epidemiology, and pathology was convened by the Society of Radiologists in Ultrasound to discuss the role of sonography in women with postmenopausal bleeding. Broad objectives of this conference were (1) to advance understanding of the utility of different diagnostic techniques for evaluating the endometrium in women with postmenopausal bleeding; (2) to formulate useful and practical guidelines for evaluation of women with postmenopausal bleeding, specifically as it relates to the use of sonography; and (3) to offer suggestions for future research projects.

Setting: October 24 and 25, 2000, Washington, DC, preceding the annual Society of Radiologists in Ultrasound Advances in Sonography conference.

Characterisation of gene expression changes following permanent MCAO in the rat using subtractive hybridisation.

Failure of several putative neuroprotectants in large multicentred clinical trials has re-focussed attention on the predictability of pre-clinical animal models of stroke. Model characterisation and relationship to heterogeneous patient sub-groups remains of paramount importance. Information gained from magnetic resonance imaging (MRI) signatures indicates that the Zea Longa model of rat middle cerebral artery occlusion may be more representative of slowly evolving infarcts.

Nitric oxide potentiates response of trigeminal neurones to dural or facial stimulation in the rat.

Infusing glyceryl trinitrate as a donor molecule, we have used electrophysiological and c-fos immunostaining techniques to study the effects of nitric oxide on neurones in the nucleus trigeminalis caudalis. Following infusion of glyceryl trinitrate, responses of neurones to electrical stimulation of periorbital cutaneous afferents were potentiated and threshold for activation of neurones by stimulation of dural afferents was reduced. Expression of c-fos was unchanged by glyceryl trinitrate compared to saline controls.