Muscarinic Modulation of Morphologically Identified Glycinergic Neurons in the Mouse PreBötzinger Complex

The cholinergic system plays an essential role in central respiratory control, but the underlying mechanisms remain elusive. We used whole-cell recordings in brainstem slices from juvenile mice expressing enhanced green fluorescent protein (EGFP) under the control of the glycine transporter type 2 (GlyT2) promoter, to examine muscarinic modulation of morphologically identified glycinergic neurons in the preBötzinger complex (preBötC), an area critical for central inspiratory rhythm generation. Biocytin-filled reconstruction of glycinergic neurons revealed that the majority of them had few primary dendrites and had axons arborized within their own dendritic field. Few glycinergic neurons had axon collaterals extended towards the premotor/motor areas or ran towards the contralateral preBötC, and had more primary dendrites and more compact dendritic trees. Spontaneously active glycinergic neurons fired regular spikes, or less frequently in a “burst-like” pattern at physiological potassium concentration. Muscarine suppressed firing in the majority of regular spiking neurons via M2 receptor activation while enhancing the remaining neurons through M1 receptors. Interestingly, rhythmic bursting was augmented by muscarine in a small group of glycinergic neurons. In contrast to its heterogeneous modulation of glycinergic neuronal excitability, muscarine generally depressed inhibitory and excitatory synaptic inputs onto both glycinergic and non-glycinergic preBötC neurons, with a stronger effect on inhibitory input. Notably, presynaptic muscarinic attenuation of excitatory synaptic input was dependent on M1 receptors in glycinergic neurons and on M2 receptors in non-glycinergic neurons. Additional field potential recordings of excitatory synaptic potentials in the M2 receptor knockout mice indicate that glycinergic and non-glycinergic neurons contribute equally to the general suppression by muscarine of excitatory activity in preBötC circuits. In conclusion, our data show that preBötC glycinergic neurons are morphologically heterogeneous, and differ in the properties of synaptic transmission and muscarinic modulation in comparison to non-glycinergic neurons. The dominant and cell-type-specific muscarinic inhibition of synaptic neurotransmission and spiking may contribute to central respiratory disturbances in high cholinergic states

A selected ion flow tube study of the ion-molecule reactions of monochloroethene, trichloroethene and tetrachloroethene

Data for the rate coefficients and product cations of the reactions of a large number of atomic and small molecular cations with monochloroethene, trichloroethene and tetrachloroethene in a selected ion flow tube at 298 K are reported. The recombination energy of the ions range from 6.27 eV (H$_3$O$^+$) through to 21.56 eV (Ne$^+$). Collisional rate coefficients are calculated by modified average dipole orientation theory and compared with experimental values. Thermochemistry and mass balance predict the most feasible neutral products. Together with previously reported results for the three isomers of dichloroethene (J. Phys. Chem. A., 2006, 110, 5760), the fragment ion branching ratios have been compared with those from threshold photoelectron photoion coincidence spectroscopy over the photon energy range 9-22 eV to determine the importance or otherwise of long-range charge transfer. For ions with recombination energy in excess of the ionisation energy of the chloroethene, charge transfer is energetically allowed. The similarity of the branching ratios from the two experiments suggest that long-range charge transfer is dominant. For ions with recombination energy less than the ionisation energy, charge transfer is not allowed; chemical reaction can only occur following formation of an ion-molecule complex, where steric effects are more significant. The products that are now formed and their percentage yield is a complex interplay between the number and position of the chlorine atoms with respect to the C=C bond, where inductive and conjugation effects can be important

Excitatory Effects of Calcitonin Gene-Related Peptide (CGRP) on Superficial Sp5C Neurons in Mouse Medullary Slices

The neuromodulator calcitonin gene-related peptide (CGRP) is known to facilitate nociceptive transmission in the superficial laminae of the spinal trigeminal nucleus caudalis (Sp5C). The central effects of CGRP in the Sp5C are very likely to contribute to the activation of central nociceptive pathways leading to attacks of severe headaches like migraine. To examine the potential impacts of CGRP on laminae I/II neurons at cellular and synaptic levels, we performed whole-cell patch-clamp recordings in juvenile mouse brainstem slices. First, we tested the effect of CGRP on cell excitability, focusing on neurons with tonically firing action potentials upon depolarizing current injection. CGRP (100 nM) enhanced tonic discharges together with membrane depolarization, an excitatory effect that was significantly reduced when the fast synaptic transmissions were pharmacologically blocked. However, CGRP at 500 nM was capable of exciting the functionally isolated cells, in a nifedipine-sensitive manner, indicating its direct effect on membrane intrinsic properties. In voltage-clamped cells, 100 nM CGRP effectively increased the frequency of excitatory synaptic inputs, suggesting its preferential presynaptic effect. Both CGRP-induced changes in cell excitability and synaptic drives were prevented by the CGRP receptor inhibitor BIBN 4096BS. Our data provide evidence that CGRP increases neuronal activity in Sp5C superficial laminae by dose-dependently promoting excitatory synaptic drive and directly enhancing cell intrinsic properties. We propose that the combination of such pre- and postsynaptic actions of CGRP might underlie its facilitation in nociceptive transmission in situations like migraine with elevated CGRP levels

Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dyslipidemic subjects.

One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance.Nome correto do segundo autor: MANDARINO, J. M. G

Self-management programmes in temporomandibular disorders: results from an international Delphi process

Self-management (SM) programmes are commonly used for initial treatment of patients with temporomandibular disorders (TMD). The programmes described in the literature, however, vary widely with no consistency in terminology used, components of care or their definitions. The aims of this study were therefore to construct an operationalised definition of self-management appropriate for the treatment of patients with TMD, identify the components of that self-management currently being used and create sufficiently clear and non-overlapping standardised definitions for each of those components. A four-round Delphi process with eleven international experts in the field of TMD was conducted to achieve these aims. In the first round, the participants agreed upon six principal concepts of self-management. In the remaining three rounds, consensus was achieved upon the definition and the six components of self-management. The main components identified and agreed upon by the participants to constitute the core of a SM programme for TMD were as follows: education; jaw exercises; massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. This Delphi process has established the principal concepts of self-management, and a standardised definition has been agreed with the following components for use in clinical practice: education; self-exercise; self-massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. The consensus-derived concepts, definitions and components of SM offer a starting point for further research to advance the evidence base for, and clinical utility of, TMD SM

Fuzzy modelling of acid mine drainage environments using geochemical, ecological and mineralogical indicators

Fuzzy logic was applied to model acid mine drainage (AMD) and to obtain a classification index of the environmental impact in a contaminated riverine system. The data set used to develop this fuzzy model (a fuzzy classifier) concerns an abandoned mine in Northern Portugal— Valdarcas mining site. Here, distinctive drainage environments (spatial patterns) can be observed based on the AMD formed in the sulphide-rich waste-dumps. Such environments were established, as the effluent flows through the mining area, using several kinds of indicators. These are physical–chemical, ecological and mineralogical parameters, being expressed in a quantitative or qualitative basis. The fuzzy classifier proposed in this paper is a min– max fuzzy inference system, representing the spatial behaviour of those indicators, using the AMD environments as patterns. As they represent different levels (classes) of contamination, the fuzzy classifier can be used as a tool, allowing a more reasonable approach, compared with classical models, to characterize the environmental impact caused by AMD. In a general way it can be applied to other sites where sulphide-rich waste-dumps are promoting the pollution of superficial water through the generation of AMD

Database computing in HEP. Progress report

The major SSC experiments are expected to produce up to 1 Petabyte of data per year each. Once the primary reconstruction is completed by farms of inexpensive processors. I/O becomes a major factor in further analysis of the data. We believe that the application of database techniques can significantly reduce the I/O performed in these analyses. We present examples of such I/O reductions in prototype based on relational and object-oriented databases of CDF data samples

Electric toothbrush application is a reliable and valid test for differentiating temporomandibular disorders pain patients from controls

<p>Abstract</p> <p>Background</p> <p>Current methods for identifying patients with pain hypersensitivity are sufficiently complex to limit their widespread application in clinical settings. We assessed the reliability and validity of a simple multi-modal vibrotactile stimulus, applied using an electric toothbrush, to evaluate its potential as a screening tool for central sensitization.</p> <p>Methods</p> <p>Fourteen female temporomandibular disorders (TMD) subjects with myofascial pain (RDC/TMD Ia or Ib) and arthralgia (RDC/TMD IIIa) were compared to 13 pain-free controls of matched age and gender. Vibrotactile stimulus was performed with an electric toothbrush, applied with 1 pound pressure for 30 seconds in four locations: over the lateral pole of the temporomandibular joint, masseter, temporalis, and mid-ventral surface of forearm. Pain intensity (0–10) was recorded following the stimulus at 0, 15, 30, and 60 seconds. Test-retest reliability was assessed with measurements from 8 participants, taken 2–12 hours apart. Case versus control differentiation involved comparison of area under the curve (AUC). A receiver operating characteristic (ROC) curve was used to determine cutoff AUC scores for maximum sensitivity and specificity for this multi-modal vibrotactile stimulus.</p> <p>Results</p> <p>Test-retest reliability resulted in an ICC of 0.87 for all 4 pooled sites. ROC-determined AUC cutoff scores resulted in a sensitivity of 57% and specificity of 92% for all 4 pooled sites.</p> <p>Conclusion</p> <p>The electric toothbrush stimulus had excellent test-retest reliability. Validity of the scores was demonstrated with modest sensitivity and good specificity for differentiating TMD pain patients from controls, which are acceptable properties for a screening test.</p