Ramping Position to Aid Non-invasive Ventilation (NIV) in Obese Patients in the ICU.

Introduction: The ramping position is recommended to facilitate pre-oxygenation and mask ventilation of obese patients in anaesthetics via improving the airway alignment.

Presentation Of Case Series: Two cases of obese patients admitted to the intensive care unit (ICU) with type 2 respiratory failure. Both cases showed obstructive breathing patterns on non-invasive ventilation (NIV) and failed resolution of hypercapnia.

Application of the common base method to regression and analysis of covariance (ANCOVA) in qPCR experiments and subsequent relative expression calculation.

Background: Quantitative polymerase chain reaction (qPCR) is the technique of choice for quantifying gene expression. While the technique itself is well established, approaches for the analysis of qPCR data continue to improve.

Results: Here we expand on the common base method to develop procedures for testing linear relationships between gene expression and either a measured dependent variable, independent variable, or expression of another gene.

Evaluation of usage of virtual microscopy for the study of histology in the medical, dental, and veterinary undergraduate programs of a UK University.

This article describes the introduction of a virtual microscope (VM) that has allowed preclinical histology teaching to be fashioned to better suit the needs of approximately 900 undergraduate students per year studying medicine, dentistry, or veterinary science at the University of Bristol, United Kingdom. Features of the VM implementation include: (1) the facility for students and teachers to make annotations on the digital slides; (2) in-house development of VM-based quizzes that are used for both formative and summative assessments; (3) archiving of teaching materials generated each year, enabling students to access their personalized learning resources throughout their programs; and (4) retention of light microscopy capability alongside the VM. Student feedback on the VM is particularly positive about its ease of use, the value of the annotation tool, the quizzes, and the accessibility of all components off-campus.

Evidence for a common mechanism for spontaneous rhythmic contraction and myogenic contraction induced by quick stretch in detrusor smooth muscle.

Detrusor smooth muscle exhibits myogenic contraction in response to a quick stretch (QS) as well as spontaneous rhythmic contraction (SRC); however, whether the same population of actomyosin crossbridges with a common regulatory mechanism is responsible for these two types of contraction has not been determined. Detrusor strips from New Zealand white rabbit bladders were allowed to develop SRC at a reference muscle length (L ref), or rhythmic contraction (RC) was induced with tetraethylammonium (TEA). Multiple 10-msec stretches of 15% L ref were then imposed at L ref randomly during the rhythm cycle, and the nadir-to-peak (NTP) tension amplitude of the resulting myogenic contraction was measured.

IFPA Meeting 2010 Workshops Report II: Placental pathology; trophoblast invasion; fetal sex; parasites and the placenta; decidua and embryonic or fetal loss; trophoblast differentiation and syncytialisation.

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1.

Chronic secondary hypersensitivity of dorsal horn neurones following inflammation of the knee joint.

Intra-articular injection of Freund's complete adjuvant (FCA) into the rat knee joint produces a swelling of the joint and long lasting hypersensitivity. In this study we have used this model and in vivo electrophysiology to investigate the time course of spinal changes underlying chronic secondary hypersensitivity, by stimulating the ankle joint (an area outside the site of primary hypersensitivity), and have compared the results with behavioural data from the same population of animals at 4-8, 13-17 and 55-59 days following FCA injection. The magnitude of responses and the proportion of dorsal horn neurones receiving inputs from A beta- A delta- and C-fibre afferents were monitored.

NMDA antagonists and neuropathic pain--multiple drug targets and multiple uses.

NMDA (N-methyl-D-aspartate) receptors are one class of ionotropic receptor for the ubiquitous excitatory neurotransmitter L-glutamate. The receptor is made up of four protein subunits combined from a larger library of proteins, which gives this receptor a great deal of variability. This explains the large number of modulatory sites, a variety of sites at which antagonists can interact, and therefore a number of potential drug targets.

Investigation of systemic bupivacaine toxicity using the in situ perfused working heart-brainstem preparation of the rat.

Background: The inadvertent systemic administration of bupivacaine has been associated with fatal cardiovascular collapse. Systemic bupivacaine may affect neural control of the cardiovascular system in addition to having toxic actions on the heart. The study tested the hypothesis that systemic bupivacaine has toxic effects on brainstem cardiorespiratory control.

Systemic pre-treatment with a group II mGlu agonist, LY379268, reduces hyperalgesia in vivo.

1. Previous studies investigating the role of metabotropic glutamate (mGlu) receptors in nociceptive processing have been hampered by the lack of systemically active, selective, ligands. This study investigates the possible analgesic and/or anti-hyperalgesic properties of the most potent compound to date that has systemic agonist activity at group II mGlu receptors, LY379268.

NMDA receptor antagonists as analgesics: focus on the NR2B subtype.

Ifenprodil and a group of related compounds are selective antagonists of NR2B-containing NMDA receptors. These compounds are antinociceptive in a variety of preclinical pain models and have a much lower side-effect profile compared with other NMDA receptor antagonists. It remains unclear whether the improved safety of these compounds is due to their subtype selectivity or to a unique mode of inhibition of the receptor.

The in vivo relevance of the varied channel-blocking properties of uncompetitive NMDA antagonists: tests on spinal neurones.

The voltage dependence and channel-blocking kinetics of uncompetitive NMDA receptor antagonists have been well-described using in vitro techniques, but there is little evidence concerning the functional significance of these properties in vivo. We have now compared the effects of NMDA antagonists that display varied profiles of voltage-dependent block in vitro, on responses of spinal neurones in anaesthetised rats. The compounds examined were the uncompetitive channel blockers memantine, ketamine and MK-801 and, for comparison, an antagonist that acts at the strychnine-insensitive glycine binding site (MRZ 2/502).

Effects of NMDA receptor antagonists on nociceptive responses in vivo: comparison of antagonists acting at the glycine site with uncompetitive antagonists.

We have shown that members of a new series of tricyclic pyridophthalazine diones, defined as glycineB site NMDA antagonists in vitro, are selective and systemically active NMDA antagonists in vivo. In electrophysiological tests in alpha-chloralose anaesthetised rats, these compounds reduced nociceptive reflex responses. In conscious rats they displayed analgesic properties.

Actions of kainate and AMPA selective glutamate receptor ligands on nociceptive processing in the spinal cord.

Kainate receptors expressing the GluR5 subunit of glutamate receptor are present at high levels on small diameter primary afferent neurones that are considered to mediate nociceptive inputs. This suggests that GluR5 selective ligands could be novel analgesic agents. The role of kainate receptors on C fibre primary afferents has therefore been probed using three compounds that are selective for homomeric GluR5 receptors.

Coupling of sympathetic and somatic motor outflows from the spinal cord in a perfused preparation of adult mouse in vitro.

1. The relationship between sympathetic and somatic motor outflows from thoraco-lumbar spinal cord was investigated in a novel arterially perfused trunk-hindquarters preparation of adult mouse. 2.

Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization.

A series of novel tricyclic pyrido-phthalazine-dione derivatives was tested for antagonistic effects at the strychnine-insensitive modulatory site of the N-methyl-D-aspartate (NMDA) receptor (glycineB). All compounds displaced [3H]MDL-105,519 binding to rat cortical membranes with IC50 values of between 90 nM and 3.6 microM.

An arterially-perfused trunk-hindquarters preparation of adult mouse in vitro.

We describe a preparation of arterially-perfused spinal cord with attached hindquarters, taken from adult mouse. This is the first preparation of adult mammalian spinal cord tissue to have the advantages of an in vitro approach whilst retaining intact intraspinal circuitry, sensory inputs, and somatic and sympathetic segmental outputs. The functional integrity of the preparation has been demonstrated by the motor and sympathetic reflexes that can readily be evoked by peripheral noxious thermal, mechanical and electrical stimuli, and also by bladder distension.

Stimulus intensity, cell excitation and the N-methyl-D-aspartate receptor component of sensory responses in the rat spinal cord in vivo.

The importance of receptors for N-methyl-D-aspartate in synaptic plasticity and in triggering long-term pronociceptive changes is explained by their voltage-dependence. This suggests that their contribution to acute nociceptive responses would be determined both by the magnitude of synaptic input and by the level of background excitation. We have now examined the role of N-methyl-D-aspartate receptors in acute nociceptive transmission in the spinal cord.

Effect of agmatine on spinal nociceptive reflexes: lack of interaction with alpha2-adrenoceptor or mu-opioid receptor mechanisms.

Agmatine has been tested i.v. in alpha-chloralose anaesthetised rats for its effects on spinal nociceptive reflexes evoked by mechanical and electrical stimuli.

Metabotropic glutamate receptor antagonists, like GABA(B) antagonists, potentiate dorsal root-evoked excitatory synaptic transmission at neonatal rat spinal motoneurons in vitro.

Recordings of whole-cell synaptic current responses elicited by electrical stimulation of dorsal roots were made from motoneurons, identified by antidromic invasion, in isolated spinal cord preparations from five- to eight-day-old Wistar rats. Supramaximal electrical stimulation of the dorsal root evoked complex excitatory postsynaptic currents with mean latencies (+/- S.E.

Antagonism of mGlu receptors and potentiation of EPSCs at rat spinal motoneurones in vitro.

The patch-clamp technique has been used to record synaptic responses, elicited by electrical stimulation of dorsal roots, in 28 single motoneurones of in vitro spinal cord preparations from neonate (P5 to P8) rats. The effects of (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (200 microM), a potent antagonist at L-2-amino-4-phosphonobutanoate (AP4)-sensitive receptors, and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (500 microM), which is a less selective antagonist of mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression of EPSCs. The EC50 for depression of EPSCs by AP4 (1.

Reversal by naloxone of the spinal antinociceptive actions of a systemically-administered NSAID.

1. Possible interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and endogenous opioids were examined in electrophysiological experiments in alpha-chloralose anaesthetized spinalized rats without or with carrageenan-induced acute inflammation of one hindpaw. Spinal reflex responses, monitored as single motor unit discharges, were elicited by noxious pinch and electrical stimuli.

Thyrotropin-releasing hormone facilitates spinal nociceptive responses by potentiating NMDA receptor-mediated transmission.

The interaction of thyrotropin-releasing hormone (TRH) with NMDA receptor-mediated responses has been investigated in alpha-chloralose-anaesthetized spinalized rats with respect to its relevance to spinal nociceptive transmission. The effects of TRH and of the uncompetitive NMDA antagonist ketamine were tested on responses of dorsal horn wide dynamic range neurones to noxious pinch, heat and electrical stimuli in parallel with those to iontophoretically applied N-methyl-D-aspartate (NMDA) and AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid). Tests with NMDA blocking doses of ketamine (4 mg/kg i.

Studies of synaptic transmission in vivo: indirect versus direct effects of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid/kainate antagonists on rat spinal sensory responses.

The (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline (NBQX) and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) were examined by microiontophoretic administration in electrophysiological tests on spinal neurones in alpha-chloralose anaesthetized rats. The antagonists significantly reduced extracellularly recorded nociceptive and non-nociceptive responses, as expected; concurrently they reduced background discharge. When the background discharge rate was held constant, the antagonists no longer significantly reduced the evoked responses.

NMDA-receptor contribution to spinal nociceptive reflexes: influence of stimulus parameters and of preparatory surgery.

The contribution of NMDA receptors to nociceptive reflexes has been assessed both in awake rats and in electrophysiological tests on alpha-chloralose anaesthetized spinalized rats prepared with different degrees of surgery. Single motor unit activity was recorded in response to alternating noxious mechanical and electrical stimuli applied to one hindpaw, and the results compared with paw pressure withdrawal reflexes in awake rats. There was little contribution by NMDA receptors to nociceptive paw pinch responses either in awake rats or in rats prepared with minimal surgery, but following extensive lumbar surgery the contribution increased significantly to a level similar to that seen in the wind-up component of responses elicited by electrical stimulation.

Cutaneous responsiveness of lumbar spinal neurons in awake and halothane-anesthetized sheep.

1. To compare the responsiveness of lumbar spinal neurons to peripheral sensory stimuli under normal physiological conditions and under halothane anesthesia, we performed a study in sheep that were prepared chronically. This permitted recordings to be made in the same animals either when they were awake and free from recent surgery, drugs, and training and only partially restrained or when they were anesthetized with halothane.