Albrecht, Jessica; Kopietz, Rainer; Frasnelli, Johannes; Wiesmann, Martin; Hummel, Thomas; Lundström, Johan N.
2009-01-01
Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO2), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices – a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO2 stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing. PMID:19913573
Song, Zhi-Xiu; Qian, Wei; Wu, Yu-Quan; Sun, Fang-Jie; Fei, Jun; Huang, Run-Sheng; Fang, Jing-Yu; Wu, Cai-Zhen; An, You-Ming; Wang, Daxin; Yang, Jun
2014-01-01
To understand the mechanism of the gamma knife treating the trigeminal neuralgia. Using the MASEP-SRRS type gamma knife treatment system, 140 Chinese patients with trigeminal neuralgia (NT) were treated in our hospital from 2002 to 2010, in which the pain relief rate reached 95% and recurrence rate was 3% only. We investigated the effect of the gamma knife treatment on the trigeminal nerve root in 20 Chinese patients with primary trigeminal neuralgia by the magnetic resonance imager (MRI) observation. 1) The cross-sectional area of trigeminal nerve root became smaller and MRI signals were lower in the treatment side than those in the non-treatment side after the gamma knife treatment of primary trigeminal neuralgia; 2) in the treatment side, the cross-sectional area of the trigeminal nerve root decreased significantly after the gamma knife treatment; 3) there was good correlation between the clinical improvement and the MRI findings; and 4) the straight distance between the trigeminal nerve root and the brainstem did not change after the gamma knife treatment. The pain relief induced the gamma knife radiosurgery might be related with the atrophy of the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.
Overview of atomic layer etching in the semiconductor industry
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kanarik, Keren J., E-mail: keren.kanarik@lamresearch.com; Lill, Thorsten; Hudson, Eric A.
2015-03-15
Atomic layer etching (ALE) is a technique for removing thin layers of material using sequential reaction steps that are self-limiting. ALE has been studied in the laboratory for more than 25 years. Today, it is being driven by the semiconductor industry as an alternative to continuous etching and is viewed as an essential counterpart to atomic layer deposition. As we enter the era of atomic-scale dimensions, there is need to unify the ALE field through increased effectiveness of collaboration between academia and industry, and to help enable the transition from lab to fab. With this in mind, this article providesmore » defining criteria for ALE, along with clarification of some of the terminology and assumptions of this field. To increase understanding of the process, the mechanistic understanding is described for the silicon ALE case study, including the advantages of plasma-assisted processing. A historical overview spanning more than 25 years is provided for silicon, as well as ALE studies on oxides, III–V compounds, and other materials. Together, these processes encompass a variety of implementations, all following the same ALE principles. While the focus is on directional etching, isotropic ALE is also included. As part of this review, the authors also address the role of power pulsing as a predecessor to ALE and examine the outlook of ALE in the manufacturing of advanced semiconductor devices.« less
Cellular Localization of Aquaporin-1 in the Human and Mouse Trigeminal Systems
Gu, Minxia; Marshall, Charles; Ding, Jiong; Hu, Gang; Xiao, Ming
2012-01-01
Previous studies reported that a subpopulation of mouse and rat trigeminal neurons express water channel aquaporin-1 (AQP1). In this study we make a comparative investigation of AQP1 localization in the human and mouse trigeminal systems. Immunohistochemistry and immunofluorescence results showed that AQP1 was localized to the cytoplasm and cell membrane of some medium and small-sized trigeminal neurons. Additionally, AQP1 was found in numerous peripheral trigeminal axons of humans and mice. In the central trigeminal root and brain stem, AQP1 was specifically expressed in astrocytes of humans, but was restricted to nerve fibers within the central trigeminal root and spinal trigeminal tract and nucleus in mice. Furthermore, AQP1 positive nerve fibers were present in the mucosal and submucosal layers of human and mouse oral tissues, but not in the muscular and subcutaneous layers. Fluorogold retrograde tracing demonstrated that AQP1 positive trigeminal neurons innervate the mucosa but not skin of cheek. These results reveal there are similarities and differences in the cellular localization of AQP1 between the human and mouse trigeminal systems. Selective expression of AQP1 in the trigeminal neurons innervating the oral mucosa indicates an involvement of AQP1 in oral sensory transduction. PMID:23029502
Trigeminal nerve anatomy in neuropathic and non-neuropathic orofacial pain patients.
Wilcox, Sophie L; Gustin, Sylvia M; Eykman, Elizabeth N; Fowler, Gordon; Peck, Christopher C; Murray, Greg M; Henderson, Luke A
2013-08-01
Trigeminal neuralgia, painful trigeminal neuropathy, and painful temporomandibular disorders (TMDs) are chronic orofacial pain conditions that are thought to have fundamentally different etiologies. Trigeminal neuralgia and neuropathy are thought to arise from damage to or pressure on the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. This study sought to assess the volume and microstructure of the trigeminal nerve in these 3 conditions. In 9 neuralgia, 18 neuropathy, 20 TMD, and 26 healthy controls, the trigeminal root entry zone was selected on high-resolution T1-weighted magnetic resonance images and the volume (mm(3)) calculated. Additionally, using diffusion-tensor images (DTIs), the mean diffusivity and fractional anisotropy values of the trigeminal nerve root were calculated. Trigeminal neuralgia patients displayed a significant (47%) decrease in nerve volume but no change in DTI values. Conversely, trigeminal neuropathy subjects displayed a significant (40%) increase in nerve volume but again no change in DTI values. In contrast, TMD subjects displayed no change in volume or DTI values. The data suggest that the changes occurring within the trigeminal nerve are not uniform in all orofacial pain conditions. These structural and volume changes may have implications in diagnosis and management of different forms of chronic orofacial pain. This study reveals that neuropathic orofacial pain conditions are associated with changes in trigeminal nerve volume, whereas non-neuropathic orofacial pain is not associated with any change in nerve volume. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.
Amey-Özel, Monique; von der Emde, Gerhard; Engelmann, Jacob; Grant, Kirsty
2015-04-01
The weakly electric fish Gnathonemus petersii uses its electric sense to actively probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is rich in electroreceptors. Physical measurements have demonstrated the importance of the position of the Schnauzenorgan in funneling the fish's self-generated electric field. The present study focuses on the trigeminal motor pathway that controls Schnauzenorgan movement and on its trigeminal sensory innervation and central representation. The nerves entering the Schnauzenorgan are very large and contain both motor and sensory trigeminal components as well as an electrosensory pathway. With the use of neurotracer techniques, labeled Schnauzenorgan motoneurons were found throughout the ventral main body of the trigeminal motor nucleus but not among the population of larger motoneurons in its rostrodorsal region. The Schnauzenorgan receives no motor or sensory innervation from the facial nerve. There are many anastomoses between the peripheral electrosensory and trigeminal nerves, but these senses remain separate in the sensory ganglia and in their first central relays. Schnauzenorgan trigeminal primary afferent projections extend throughout the descending trigeminal sensory nuclei, and a few fibers enter the facial lobe. Although no labeled neurons could be identified in the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic, possibly proprioceptive, pathway. In this first step toward understanding multimodal central representation of the Schnauzenorgan, no direct interconnections were found between the trigeminal sensory and electromotor command system, or the electrosensory and trigeminal motor command. The pathways linking perception to action remain to be studied. © 2014 Wiley Periodicals, Inc.
Vistoli, G; De Maddis, D; Cipak, A; Zarkovic, N; Carini, M; Aldini, G
2013-08-01
Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions; (2) to elucidate the molecular basis of their biological effects; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.
Henry, M A; Johnson, L R; Nousek-Goebl, N; Westrum, L E
1996-02-19
Calcitonin gene-related peptide (CGRP) is a neuropeptide that has been implicated in the transmission and modulation of primary afferent nociceptive stimuli. In this study, we describe the light microscopic distribution of CGRP immunoreactivity (IR) within the feline trigeminal ganglion and trigeminal nucleus of normal adult subjects and in subjects 10 and 30 days following complete retrogasserian rhizotomy. Within the trigeminal ganglion of normal subjects, cell bodies and fibers showed CGRP-IR, whereas immunoreactive fibers were rare in the central root region. Within the normal spinal trigeminal and main sensory nuclei, CGRP-IR was seen to form a reproducible pattern that varied between the different nuclei. Following rhizotomy, most, but not all, of the CGRP-IR was lost from the spinal trigeminal and main sensory nuclei, except in regions where the upper cervical roots and cranial nerves VII, IX and X project into the trigeminal nucleus. The pattern seen at 10 days contained more CGRP-IR than that seen at 30 days and suggests that degenerating fibers still show CGRP-IR. In contrast to the decrease seen in the nuclei after rhizotomy, examination of the central root that was still attached to the trigeminal ganglion showed an increase in CGRP-IR within fibers, some of which ended in growth conelike enlargements. Rhizotomy induced a dramatic increase in CGRP-IR within trigeminal motoneurons and their fibers, which was strongest 10 days after rhizotomy and weaker at 30 days, which was still stronger than normal. These results indicate that the majority of CGRP-IR found in the trigeminal nucleus originates from trigeminal primary afferents and that an upregulation of CGRP-IR occurs in trigeminal motoneurons and in regenerating fibers in the part of the central root that was still attached to the ganglion. In addition, the persistence of CGRP-IR fibers in the trigeminal nucleus provides one possible explanation for the preservation of pain in humans following trigeminal rhizotomy.
Cornelison, Lauren E.; Hawkins, Jordan L.; Durham, Paul L.
2016-01-01
Orofacial pain conditions including temporomandibular joint disorder and migraine are characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Although calcitonin gene-related peptide (CGRP) is implicated in the development of central sensitization, the pathway by which elevated spinal cord CGRP levels promote peripheral sensitization of primary trigeminal nociceptive neurons is not well understood. The goal of this study was to investigate the role of CGRP in promoting bidirectional signaling within the trigeminal system to mediate sensitization of primary trigeminal ganglion nociceptive neurons. Adult male Sprague Dawley rats were injected in the upper spinal cord with CGRP or co-injected with the receptor antagonist CGRP8-37 or KT 5720, an inhibitor of protein kinase A (PKA). Nocifensive head withdrawal response to mechanical stimulation of trigeminal nerves was investigated using von Frey filaments. Expression of PKA, GFAP, and Iba1 in the spinal cord and P-ERK in the trigeminal ganglion was studied using immunohistochemistry. Some animals were co-injected intracisternally with CGRP and Fast Blue dye and trigeminal ganglion imaged using fluorescent microscopy. Intracisternal CGRP increased nocifensive responses to mechanical stimulation when compared to control levels. Co-injection of CGRP8-37 or KT 5720 with CGRP inhibited the nocifensive response. CGRP stimulated expression of PKA and GFAP in the spinal cord, and P-ERK in trigeminal ganglion neurons. Seven days post injection, Fast Blue was observed in trigeminal ganglion neurons and satellite glial cells. Our results demonstrate that elevated levels of CGRP in the upper spinal cord promote sensitization of primary trigeminal nociceptive neurons via a mechanism that involves activation of PKA centrally and P-ERK in trigeminal ganglion neurons. Our findings provide evidence of bidirectional signaling within the trigeminal system that can facilitate increased neuron-glia communication within the trigeminal ganglion associated with peripheral sensitization. PMID:27746346
A Case Report About Cluster-Tic Syndrome Due to Venous Compression of the Trigeminal Nerve.
de Coo, Ilse; van Dijk, J Marc C; Metzemaekers, Jan D M; Haan, Joost
2017-04-01
The term "cluster-tic syndrome" is used for the rare ipsilateral co-occurrence of attacks of cluster headache and trigeminal neuralgia. Medical treatment should combine treatment for cluster headache and trigeminal neuralgia, but is very often unsatisfactory. Here, we describe a 41-year-old woman diagnosed with cluster-tic syndrome who underwent microvascular decompression of the trigeminal nerve, primarily aimed at the "trigeminal neuralgia" part of her pain syndrome. After venous decompression of the trigeminal nerve both a decrease in trigeminal neuralgia and cluster headache attacks was seen. However, the headache did not disappear completely. Furthermore, she reported a decrease in pain intensity of the remaining cluster headache attacks. This case description suggests that venous vascular decompression in cluster-tic syndrome can be remarkably effective, both for trigeminal neuralgia and cluster headache. © 2016 American Headache Society.
Zdilla, Matthew J; Hatfield, Scott A; Mangus, Kelsey R
2016-11-01
The debilitating pain of trigeminal neuralgia often necessitates neurosurgical intervention via percutaneous transovale cannulation. While most percutaneous treatments of trigeminal neuralgia are successful, severe adverse events resulting from failure to properly cannulate the foramen ovale (FO) have been reported. With regard to specific targeting of particular trigeminal divisions (ie, V1, V2, V3, and combinations thereof), operative techniques have been described; however, these descriptions have not included specific angulation data. This anatomic study analyzed the angular relationship between the centroid and anteromedial- and posterolateral-most aspects of the FO and the boundaries of the trigeminal impression. The study is the first to detail the angular relationship between the FO boundaries and the boundaries of the trigeminal impression in dry human skulls relative to the coronal plane. The information may be used to prevent miscannulation and also target specific branches of the trigeminal nerve for optimal operative results.
Differences in individual susceptibility affect the development of trigeminal neuralgia☆
Duransoy, Yusuf Kurtuluş; Mete, Mesut; Akçay, Emrah; Selçuki, Mehmet
2013-01-01
Trigeminal neuralgia is a syndrome due to dysfunctional hyperactivity of the trigeminal nerve, and is characterized by a sudden, usually unilateral, recurrent lancinating pain arising from one or more divisions of the nerve. The most accepted pathogenetic mechanism for trigeminal neuralgia is compression of the nerve at its dorsal root entry zone or in its distal course. In this paper, we report four cases with trigeminal neuralgia due to an unknown mechanism after an intracranial intervention. The onset of trigeminal neuralgia after surgical interventions that are unrelated to the trigeminal nerve suggests that in patients with greater individual susceptibility, nerve contact with the vascular structure due to postoperative pressure and changes in cerebrospinal fluid flow may cause the onset of pain. PMID:25206428
Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.
Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F
1987-12-01
Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.
Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis.
Fröhlich, Kilian; Winder, Klemens; Linker, Ralf A; Engelhorn, Tobias; Dörfler, Arnd; Lee, De-Hyung; Hilz, Max J; Schwab, Stefan; Seifert, Frank
2018-06-01
Background It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients. Methods We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test. Results From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia. Conclusions Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.
Perception of trigeminal mixtures.
Filiou, Renée-Pier; Lepore, Franco; Bryant, Bruce; Lundström, Johan N; Frasnelli, Johannes
2015-01-01
The trigeminal system is a chemical sense allowing for the perception of chemosensory information in our environment. However, contrary to smell and taste, we lack a thorough understanding of the trigeminal processing of mixtures. We, therefore, investigated trigeminal perception using mixtures of 3 relatively receptor-specific agonists together with one control odor in different proportions to determine basic perceptual dimensions of trigeminal perception. We found that 4 main dimensions were linked to trigeminal perception: sensations of intensity, warmth, coldness, and pain. We subsequently investigated perception of binary mixtures of trigeminal stimuli by means of these 4 perceptual dimensions using different concentrations of a cooling stimulus (eucalyptol) mixed with a stimulus that evokes warmth perception (cinnamaldehyde). To determine if sensory interactions are mainly of central or peripheral origin, we presented stimuli in a physical "mixture" or as a "combination" presented separately to individual nostrils. Results showed that mixtures generally yielded higher ratings than combinations on the trigeminal dimensions "intensity," "warm," and "painful," whereas combinations yielded higher ratings than mixtures on the trigeminal dimension "cold." These results suggest dimension-specific interactions in the perception of trigeminal mixtures, which may be explained by particular interactions that may take place on peripheral or central levels. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Olfactory dysfunction affects thresholds to trigeminal chemosensory sensations.
Frasnelli, J; Schuster, B; Hummel, T
2010-01-14
Next to olfaction and gustation, the trigeminal system represents a third chemosensory system. These senses are interconnected; a loss of olfactory function also leads to a reduced sensitivity in the trigeminal chemosensory system. However, most studies so far focused on comparing trigeminal sensitivity to suprathreshold stimuli; much less data is available with regard to trigeminal sensitivity in the perithreshold range. Therefore we assessed detection thresholds for CO(2), a relatively pure trigeminal stimulus in controls and in patients with olfactory dysfunction (OD). We could show that OD patients exhibit higher detection thresholds than controls. In addition, we were able to explore the effects of different etiologies of smell loss on trigeminal detection thresholds. We could show that in younger subjects, patients suffering from olfactory loss due to head trauma are more severely impaired with regard to their trigeminal sensitivity than patients with isolated congenital anosmia. In older patients, we could not observe any differences between different etiologies, probably due to the well known age-related decrease of trigeminal sensitivity. Furthermore we could show that a betterment of the OD was accompanied by decreased thresholds. This was most evident in patients with postviral OD. In conclusion, factors such as age, olfactory status and etiology of olfactory disorder can affect responsiveness to perithreshold trigeminal chemosensory stimuli. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Predicting synergy in atomic layer etching
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kanarik, Keren J.; Tan, Samantha; Yang, Wenbing
2017-03-27
Atomic layer etching (ALE) is a multistep process used today in manufacturing for removing ultrathin layers of material. In this article, the authors report on ALE of Si, Ge, C, W, GaN, and SiO 2 using a directional (anisotropic) plasma-enhanced approach. The authors analyze these systems by defining an “ALE synergy” parameter which quantifies the degree to which a process approaches the ideal ALE regime. This parameter is inspired by the ion-neutral synergy concept introduced in the 1979 paper by Coburn and Winters. ALE synergy is related to the energetics of underlying surface interactions and is understood in terms ofmore » energy criteria for the energy barriers involved in the reactions. Synergistic behavior is observed for all of the systems studied, with each exhibiting behavior unique to the reactant–material combination. By systematically studying atomic layer etching of a group of materials, the authors show that ALE synergy scales with the surface binding energy of the bulk material. This insight explains why some materials are more or less amenable to the directional ALE approach. Furthermore, they conclude that ALE is both simpler to understand than conventional plasma etch processing and is applicable to metals, semiconductors, and dielectrics.« less
Zhu, Jin; Zhang, Xin; Zhao, Hua; Tang, Yin-Da; Ying, Ting-Ting; Li, Shi-Ting
2017-09-01
To investigate the characteristics of brainstem trigeminal evoked potentials (BTEP) waveform in patients with and without trigeminal neuralgia (TN), and to discuss the utility of BTEP in patients with primary TN treated by microvascular decompression (MVD). A retrospective review of 43 patients who underwent BTEP between January 2016 and June 2016, including 33 patients with TN who underwent MVD and 10 patients without TN. Brainstem trigeminal evoked potentials characteristics of TN and non-TN were summarized, in particular to compare the BTEP changes between pre- and post-MVD, and to discover the relationship between BTEP changes and surgical outcome. Brainstem trigeminal evoked potentials can be recorded in patients without trigeminal neuralgia. Abnormal BTEP could be recorded when different branches were stimulated. After decompression, the original W2, W3 disappeared and then replaced by a large wave in most patients, or original wave poorly differentiated improved in some patients, showed as shorter latency and (or) amplitude increased. Brainstem trigeminal evoked potentials waveform of healthy side in patients with trigeminal neuralgia was similar to the waveform of patients without TN. In 3 patients, after decompression the W2, W3 peaks increased, and the latency, duration, IPLD did not change significantly. Until discharge, 87.9% (29/33) of the patients presented complete absence of pain without medication (BNI I) and 93.9% (31/33) had good pain control without medication (BNI I-II). Brainstem trigeminal evoked potentials can reflect the conduction function of the trigeminal nerve to evaluate the functional level of the trigeminal nerve conduction pathway. The improvement and restoration of BTEP waveforms are closely related to the postoperative curative effect.
Identification of Cytokines and Signaling Proteins Differentially Regulated by Sumatriptan/Naproxen
Vause, Carrie V; Durham, Paul L
2011-01-01
Summary Objectives The goal of this study was to use protein array analysis to investigate temporal regulation of stimulated cytokine expression in trigeminal ganglia and spinal trigeminal nuclei in response to cotreatment of sumatriptan and naproxen sodium or individual drug. Background Activation of neurons and glia in trigeminal ganglia and spinal trigeminal nuclei leads to increased levels of cytokines that promote peripheral and central sensitization, which are key events in migraine pathology. While recent clinical studies have provided evidence that a combination of sumatriptan and naproxen sodium is more efficacious in treating migraine than either drug alone, it is not well understood why the combination therapy is superior to monotherapy. Methods Male Sprague Dawley rats were left untreated (control), injected with capsaicin, or pre-treated with sumatriptan/naproxen, sumatriptan, or naproxen for 1 hour prior to capsaicin. Trigeminal ganglia and spinal trigeminal nuclei were isolated 2 and 24 hours after capsaicin or drug treatment and levels of 90 proteins were determined using a RayBio® Label-Based Rat Antibody Array. Results Capsaicin stimulated a >3-fold increase in expression of the majority of cytokines in trigeminal ganglia at 2 hours that was sustained at 24 hours. Significantly, treatment with sumatriptan/naproxen almost completely abolished the stimulatory effects of capsaicin at 2 and 24 hours. Capsaicin stimulated >3-fold expression of more proteins in spinal trigeminal nuclei at 24 hours when compared to 2 hours. Similarly, sumatriptan/naproxen abolished capsaicin stimulation of proteins in spinal trigeminal nuclei at 2 hours and greatly suppressed protein expression 24 hours post capsaicin injection. Interestingly, treatment with sumatriptan alone suppressed expression of different cytokines in trigeminal ganglia and spinal trigeminal nuclei than repressed by naproxen sodium. Conclusion We found that the combination of sumatriptan/naproxen was effective in blocking capsaicin stimulation of pro-inflammatory proteins implicated in the development of peripheral and central sensitization in response to capsaicin activation of trigeminal neurons. Based on our findings that sumatriptan and naproxen regulate expression of different proteins in trigeminal ganglia and spinal trigeminal nuclei, we propose that these drugs function on therapeutically distinct cellular targets to suppress inflammation and pain associated with migraine. PMID:22150557
Effect of beam channel plugging on the outcome of gamma knife radiosurgery for trigeminal neuralgia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Massager, Nicolas; Nissim, Ouzi; Murata, Noriko
2006-07-15
Purpose: We studied the influence of using plugs for brainstem protection during gamma knife radiosurgery (GKR) of trigeminal neuralgia (TN), with special emphasis on irradiation doses delivered to the trigeminal nerve, pain outcomes, and incidence of trigeminal dysfunction. Methods and Materials: A GKR procedure for TN using an anterior cisternal target and a maximum dose of 90 Gy was performed in 109 patients. For 49 patients, customized beam channel blocking (plugs) were used to reduce the dose delivered to the brainstem. We measured the mean and integrated radiation doses delivered to the trigeminal nerve and the clinical course of patientsmore » treated with and without plugs. Results: We found that blocking increases the length of trigeminal nerve exposed to high-dose radiation, resulting in a significantly higher mean dose to the trigeminal nerve. Significantly more of the patients with blocking achieved excellent pain outcomes (84% vs. 62%), but with higher incidences of moderate and bothersome trigeminal nerve dysfunction (37% mild/10% bothersome with plugs vs. 30% mild/2% bothersome without). Conclusions: The use of plugs to protect the brainstem during GKR treatment for TN increases the dose of irradiation delivered to the intracisternal trigeminal nerve root and is associated with an important increase in the incidence of trigeminal nerve dysfunction. Therefore, beam channel blocking should be avoided for 90 Gy-GKR of TN.« less
Distinct development of the trigeminal sensory nuclei in platypus and echidna.
Ashwell, Ken W S; Hardman, Craig D
2012-01-01
Both lineages of the modern monotremes have been reported to be capable of electroreception using the trigeminal pathways and it has been argued that electroreception arose in an aquatic platypus-like ancestor of both modern monotreme groups. On the other hand, the trigeminal sensory nuclear complex of the platypus is highly modified for processing tactile and electrosensory information from the bill, whereas the trigeminal sensory nuclear complex of the short-beaked echidna (Tachyglossus aculeatus) is not particularly specialized. If the common ancestor for both platypus and echidna were an electroreceptively and trigeminally specialized aquatic feeder, one would expect the early stages of development of the trigeminal sensory nuclei in both species to show evidence of structural specialization from the outset. To determine whether this is the case, we examined the development of the trigeminal sensory nuclei in the platypus and short-beaked echidna using the Hill and Hubrecht embryological collections. We found that the highly specialized features of the platypus trigeminal sensory nuclei (i.e. the large size of the principal nucleus and oral part of the spinal trigeminal nuclear complex, and the presence of a dorsolateral parvicellular segment in the principal nucleus) appear around the time of hatching in the platypus, but are never seen at any stage in the echidna. Our findings support the proposition that the modern echidna and platypus are derived from a common ancestor with only minimal trigeminal specialization and that the peculiar anatomy of the trigeminal sensory nuclei in the modern platypus emerged in the ornithorhynchids after divergence from the tachyglossids. Copyright © 2012 S. Karger AG, Basel.
Consequences of atomic layer etching on wafer scale uniformity in inductively coupled plasmas
NASA Astrophysics Data System (ADS)
Huard, Chad M.; Lanham, Steven J.; Kushner, Mark J.
2018-04-01
Atomic layer etching (ALE) typically divides the etching process into two self-limited reactions. One reaction passivates a single layer of material while the second preferentially removes the passivated layer. As such, under ideal conditions the wafer scale uniformity of ALE should be independent of the uniformity of the reactant fluxes onto the wafers, provided all surface reactions are saturated. The passivation and etch steps should individually asymptotically saturate after a characteristic fluence of reactants has been delivered to each site. In this paper, results from a computational investigation are discussed regarding the uniformity of ALE of Si in Cl2 containing inductively coupled plasmas when the reactant fluxes are both non-uniform and non-ideal. In the parameter space investigated for inductively coupled plasmas, the local etch rate for continuous processing was proportional to the ion flux. When operated with saturated conditions (that is, both ALE steps are allowed to self-terminate), the ALE process is less sensitive to non-uniformities in the incoming ion flux than continuous etching. Operating ALE in a sub-saturation regime resulted in less uniform etching. It was also found that ALE processing with saturated steps requires a larger total ion fluence than continuous etching to achieve the same etch depth. This condition may result in increased resist erosion and/or damage to stopping layers using ALE. While these results demonstrate that ALE provides increased etch depth uniformity, they do not show an improved critical dimension uniformity in all cases. These possible limitations to ALE processing, as well as increased processing time, will be part of the process optimization that includes the benefits of atomic resolution and improved uniformity.
Bakalar, Jennifer L; Barmine, Marissa; Druskin, Lindsay; Olsen, Cara H; Quinlan, Jeffrey; Sbrocco, Tracy; Tanofsky-Kraff, Marian
2018-03-02
US service members appear to be at high-risk for disordered eating. Further, the military is experiencing unprecedented prevalence of overweight and obesity. US service members also report a high prevalence of childhood adverse life event (ALE) exposure. Despite consistent links between early adversity with eating disorders and obesity, there is a dearth of research examining the association between ALE exposure and disordered eating and weight in military personnel. An online survey study was conducted in active duty personnel to examine childhood ALE history using the Life Stressor Checklist - Revised, disordered eating using the Eating Disorder Examination - Questionnaire total score, and self-reported body mass index (BMI, kg/m 2 ). Among 179 respondents, multiple indices of childhood ALE were positively associated with disordered eating. Traumatic childhood ALE and subjective impact of childhood ALE were associated with higher BMI and these associations were mediated by disordered eating. Findings support evaluating childhood ALE exposure among service members with disordered eating and weight concerns. Moreover, findings support the need for prospective research to elucidate these relationships. © 2018 Wiley Periodicals, Inc.
Lee, Seung Hwan; Koh, Jun Seok; Lee, Cheol Young
2011-06-01
A 61-year-old woman presented with typical trigeminal neuralgia (TN), caused by an aberrant posterior inferior cerebellar artery (PICA) associated with the primitive trigeminal artery (PTA). Magnetic resonance angiography and digital subtraction angiography clearly showed an anomalous artery directly originating from the PTA and coursing into the PICA territory at the cerebellum. During microvascular decompression (MVD), we confirmed and decompressed vascular compression of the trigeminal nerve by this anomalous, PICA-variant type of PTA. The PTA did not conflict with the trigeminal nerve, and the anomalous PICA only compressed the caudolateral part of the trigeminal nerve, without the more common compression at its root entry zone. This case is informative due not only to its very unusual angioanatomical variation but also to its helpfulness for surgeons preparing a MVD for a TN associated with such a rare vascular anomaly.
Diabetes mellitus in classical trigeminal neuralgia: A predisposing factor for its development.
Xu, Zhenq; Zhang, Ping; Long, Li; He, Huiy; Zhang, Jianch; Sun, Shup
2016-12-01
A higher prevalence of diabetes mellitus in classical trigeminal neuralgia patients was observed in few pilot surveys. The study was aimed to investigate whether diabetes mellitus is a predisposing factor for developing trigeminal neuralgia. Patients with classical trigeminal neuralgia were enrolled in the case study group. The control group consisted of the same number of age- and gender-matched, randomly sampled subjects without trigeminal neuralgia. Characteristics of classical trigeminal neuralgia cases were analyzed. The prevalence of diabetes mellitus in the cases and controls was calculated using the Chi-square test. The onset age ranged from 31 to 93 in 256 patients affected classical trigeminal neuralgia (162 females; 94 males) with a peak age between the fifth and seventh decade; right-side involvement and mandibular branch affliction occurred at a greater frequency. 21.9% patients in the study group was affected by diabetes mellitus compared to 12.9% of controls. The increased prevalence of diabetes mellitus in the trigeminal neuralgia group was statistically significant (P=0.01). Diabetes is a risk factor to the development of classical trigeminal neuralgia, and nerve damage duing to hyperglycemia might be the linkage to the two diseases. More works should be done to consolidate the correlation and to clarify the underlying mechanism for the positive association which would provide new insight into the pathogenesis of trigeminal neuralgia and may open new therapeutic perspectives. Copyright © 2016 Elsevier B.V. All rights reserved.
Comparison of ALE and SPH Methods for Simulating Mine Blast Effects on Structures
2010-12-01
Comparison of ALE and SPH methods for simulating mine blast effects on struc- tures Geneviève Toussaint Amal Bouamoul DRDC Valcartier Defence R&D...Canada – Valcartier Technical Report DRDC Valcartier TR 2010-326 December 2010 Comparison of ALE and SPH methods for simulating mine blast...Valcartier TR 2010-326 iii Executive summary Comparison of ALE and SPH methods for simulating mine blast effects on structures
A coupled ALE-AMR method for shock hydrodynamics
Waltz, J.; Bakosi, J.
2018-03-05
We present a numerical method combining adaptive mesh refinement (AMR) with arbitrary Lagrangian-Eulerian (ALE) mesh motion for the simulation of shock hydrodynamics on unstructured grids. The primary goal of the coupled method is to use AMR to reduce numerical error in ALE simulations at reduced computational expense relative to uniform fine mesh calculations, in the same manner that AMR has been used in Eulerian simulations. We also identify deficiencies with ALE methods that AMR is able to mitigate, and discuss the unique coupling challenges. The coupled method is demonstrated using three-dimensional unstructured meshes of up to O(10 7) tetrahedral cells.more » Convergence of ALE-AMR solutions towards both uniform fine mesh ALE results and analytic solutions is demonstrated. Speed-ups of 5-10× for a given level of error are observed relative to uniform fine mesh calculations.« less
A coupled ALE-AMR method for shock hydrodynamics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Waltz, J.; Bakosi, J.
We present a numerical method combining adaptive mesh refinement (AMR) with arbitrary Lagrangian-Eulerian (ALE) mesh motion for the simulation of shock hydrodynamics on unstructured grids. The primary goal of the coupled method is to use AMR to reduce numerical error in ALE simulations at reduced computational expense relative to uniform fine mesh calculations, in the same manner that AMR has been used in Eulerian simulations. We also identify deficiencies with ALE methods that AMR is able to mitigate, and discuss the unique coupling challenges. The coupled method is demonstrated using three-dimensional unstructured meshes of up to O(10 7) tetrahedral cells.more » Convergence of ALE-AMR solutions towards both uniform fine mesh ALE results and analytic solutions is demonstrated. Speed-ups of 5-10× for a given level of error are observed relative to uniform fine mesh calculations.« less
SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION
Gulbransen, Brian; Silver, Wayne; Finger, Tom
2008-01-01
Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. PMID:18300260
Nair, Kavitha; George, Thomas; El Beltagi, Ahmed
2015-01-01
Malignant trigeminal neuralgia due to perineural spread along the branches of the trigeminal nerve, is known to commonly occur secondary to squamous cell carcinomas, lymphomas and adenoid cystic carcinomas in the head and neck region. Rarely metastases to the trigeminal nerve have been reported in breast cancer, prostate cancer and colon cancer. To the best of our knowledge trigeminal neuropathy due to skull base metastases and perineural spread along the maxillary (V2) and mandibular (V3) branches of the trigeminal nerve, secondary to colon cancer, has not been previously reported. The diagnosis in our index case was made on magnetic resonance imaging, and patient was treated accordingly by fractionated stereotactic radiotherapy, with subsequent relief of her pain. PMID:26629299
Azevedo, Bruna Cestari; Morel, Lucas Junqueira Freitas; Carmona, Fábio; Cunha, Thiago Mattar; Contini, Silvia Helena Taleb; Delprete, Piero Giuseppe; Ramalho, Fernando Silva; Crevelin, Eduardo; Bertoni, Bianca Waléria; França, Suzelei Castro; Borges, Marcos Carvalho; Pereira, Ana Maria Soares
2018-05-23
Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids. To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects. Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined. Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200 mg kg -1 , respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200 mg kg -1 reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100 mg kg -1 respectively. The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine model of asthma. Although ABE and ALE exhibited distinct chemical compositions, both extracts inhibited the production of pro-inflammatory cytokines in vitro. In vivo assays revealed that ABE was more effective in treating asthmatic inflammation while ALE was more successful in controlling respiratory mechanics. Both extracts may have promising applications in the phytotherapy of allergic asthma. Copyright © 2018 Elsevier B.V. All rights reserved.
Insensitive Munitions Modeling Improvement Efforts
2010-10-01
LLNL) ALE3D . Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to...codes most commonly used by munition designers are CTH and the SIERRA suite of codes produced by Sandia National Labs (SNL) and ALE3D produced by... ALE3D , a LLNL developed code, is also used by various DoD participants. It was however, designed differently than either CTH or Sierra. ALE3D is a
Schmidt, K; Forkmann, K; Sinke, C; Gratz, M; Bitz, A; Bingel, U
2016-07-01
Compared to peripheral pain, trigeminal pain elicits higher levels of fear, which is assumed to enhance the interruptive effects of pain on concomitant cognitive processes. In this fMRI study we examined the behavioral and neural effects of trigeminal (forehead) and peripheral (hand) pain on visual processing and memory encoding. Cerebral activity was measured in 23 healthy subjects performing a visual categorization task that was immediately followed by a surprise recognition task. During the categorization task subjects received concomitant noxious electrical stimulation on the forehead or hand. Our data show that fear ratings were significantly higher for trigeminal pain. Categorization and recognition performance did not differ between pictures that were presented with trigeminal and peripheral pain. However, object categorization in the presence of trigeminal pain was associated with stronger activity in task-relevant visual areas (lateral occipital complex, LOC), memory encoding areas (hippocampus and parahippocampus) and areas implicated in emotional processing (amygdala) compared to peripheral pain. Further, individual differences in neural activation between the trigeminal and the peripheral condition were positively related to differences in fear ratings between both conditions. Functional connectivity between amygdala and LOC was increased during trigeminal compared to peripheral painful stimulation. Fear-driven compensatory resource activation seems to be enhanced for trigeminal stimuli, presumably due to their exceptional biological relevance. Copyright © 2016 Elsevier Inc. All rights reserved.
Painful Traumatic Trigeminal Neuropathy.
Rafael, Benoliel; Sorin, Teich; Eli, Eliav
2016-08-01
This article discusses neuropathic pain of traumatic origin affecting the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy by the International Headache Society and replaces atypical odontalgia, deafferentation pain, traumatic neuropathy, and phantom toothache. The discussion emphasizes the diagnosis and the early and late management of injuries to the trigeminal nerve and subsequent painful conditions. Copyright © 2016 Elsevier Inc. All rights reserved.
[Influence of trigeminal nerve lesion on facial growth: study of two cases of Goldenhar syndrome].
Darris, Pierre; Treil, Jacques; Marchal-Sixou, Christine; Baron, Pascal
2015-06-01
This cases report confirms the hypothesis that embryonic and maxillofacial growth are influenced by the peripheral nervous system, including the trigeminal nerve (V). So, it's interesting to use the stigma of the trigeminal nerve as landmarks to analyze the maxillofacial volume and understand its growth. The aim of this study is to evaluate the validity of the three-dimensional cephalometric analysis of Treil based on trigeminal landmarks. The first case is a caucasian female child with Goldenhar syndrome. The second case is a caucasian male adult affected by the same syndrome. In both cases, brain MRI showed an unilateral trigeminal nerve lesion, ipsilateral to the facial dysmorphia. The results of this radiological study tend to prove the primary role of the trigeminal nerve in craniofacial growth. These cases demonstrate the validity of the theory of Moss. They are one of anatomo-functional justifications of the three-dimensional cephalometric biometry of Treil based on trigeminal nerve landmarks. © EDP Sciences, SFODF, 2015.
Solitary chemoreceptor cell survival is independent of intact trigeminal innervation.
Gulbransen, Brian; Silver, Wayne; Finger, Thomas E
2008-05-01
Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al. [2003] Proc Natl Acad Sci USA 100:8981-8986). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al. [2003]) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. (c) 2008 Wiley-Liss, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fisher, A. C.; Bailey, D. S.; Kaiser, T. B.
2015-02-01
Here, we present a novel method for the solution of the diffusion equation on a composite AMR mesh. This approach is suitable for including diffusion based physics modules to hydrocodes that support ALE and AMR capabilities. To illustrate, we proffer our implementations of diffusion based radiation transport and heat conduction in a hydrocode called ALE-AMR. Numerical experiments conducted with the diffusion solver and associated physics packages yield 2nd order convergence in the L 2 norm.
ALE3D: An Arbitrary Lagrangian-Eulerian Multi-Physics Code
DOE Office of Scientific and Technical Information (OSTI.GOV)
Noble, Charles R.; Anderson, Andrew T.; Barton, Nathan R.
ALE3D is a multi-physics numerical simulation software tool utilizing arbitrary-Lagrangian- Eulerian (ALE) techniques. The code is written to address both two-dimensional (2D plane and axisymmetric) and three-dimensional (3D) physics and engineering problems using a hybrid finite element and finite volume formulation to model fluid and elastic-plastic response of materials on an unstructured grid. As shown in Figure 1, ALE3D is a single code that integrates many physical phenomena.
Vidgren, Virve; Ruohonen, Laura; Londesborough, John
2005-12-01
Maltose and maltotriose are the major sugars in brewer's wort. Brewer's yeasts contain multiple genes for maltose transporters. It is not known which of these express functional transporters. We correlated maltose transport kinetics with the genotypes of some ale and lager yeasts. Maltose transport by two ale strains was strongly inhibited by other alpha-glucosides, suggesting the use of broad substrate specificity transporters, such as Agt1p. Maltose transport by three lager strains was weakly inhibited by other alpha-glucosides, suggesting the use of narrow substrate specificity transporters. Hybridization studies showed that all five strains contained complete MAL1, MAL2, MAL3, and MAL4 loci, except for one ale strain, which lacked a MAL2 locus. All five strains also contained both AGT1 (coding a broad specificity alpha-glucoside transporter) and MAL11 alleles. MPH genes (maltose permease homologues) were present in the lager but not in the ale strains. During growth on maltose, the lager strains expressed AGT1 at low levels and MALx1 genes at high levels, whereas the ale strains expressed AGT1 at high levels and MALx1 genes at low levels. MPHx expression was negligible in all strains. The AGT1 sequences from the ale strains encoded full-length (616 amino acid) polypeptides, but those from both sequenced lager strains encoded truncated (394 amino acid) polypeptides that are unlikely to be functional transporters. Thus, despite the apparently similar genotypes of these ale and lager strains revealed by hybridization, maltose is predominantly carried by AGT1-encoded transporters in the ale strains and by MALx1-encoded transporters in the lager strains.
Anti-inflammatory evaluation and characterization of leaf extract of Ananas comosus.
Kargutkar, Samira; Brijesh, S
2018-04-01
Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In the present study, the potential anti-inflammatory activity of A. comosus leaf extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to preliminary qualitative phytochemical analysis and quantitative estimations of flavonoids and tannins. The components present in ALE were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and proteinase activity were assessed. Its effect on secretion of pro-inflammatory cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced inflammatory rat model was examined. The preliminary qualitative phytochemical analysis revealed presence of flavonoids, phenols, tannins, carbohydrates, glycosides, and proteins in the extract. Total flavonoids and total tannins were 0.17 ± 0.006 mg equivalent of quercetin/g of ALE and 4.04 ± 0.56 mg equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4-hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid, whereas GC-MS analysis identified the presence of campesterol and ethyl isoallocholate that have been previously reported for anti-inflammatory activity. ALE showed significant inhibition of protein denaturation and proteinase activity and also controlled secretion of tumour necrosis factor-α, interleukin-1β and prostaglandins, as well as the generation of reactive oxygen species by activated macrophages. ALE also significantly decreased carrageenan-induced acute paw edema. The study, therefore, identified the components present in ALE that may be responsible for its anti-inflammatory activity and thus demonstrated its potential use against acute inflammatory diseases.
Tan, Y-A; Zhao, X-D; Sun, Y; Hao, D-J; Zhao, J; Jiang, Y-P; Bai, L-X; Xiao, L-B
2018-04-01
Apolygus lucorum is the predominant pest of Bacillus thuringiensis (Bt) cotton in China. 20-hydroxyecdysone (20E) plays a key role in the reproduction of this insect. To better understand the mechanism underlying 20E-regulated reproduction, the nuclear hormone receptor E75 isoform-A of Ap. lucorum (Al-E75A) was cloned and its expression analysed. A 2241-bp sequence of Al-E75A cDNA encoded an open reading frame of a polypeptide with a predicted molecular mass of 69.04 kDa. Al-E75A mRNA was detected in female adult stages of Ap. lucorum with peak expression in 7-day-old animals. Al-E75A was also expressed in several tissues, particularly in the fat body and ovary. A 3.2 kb Al-E75A mRNA was detected in all tissues by Northern blot. The fecundity and longevity were significantly decreased in female adults treated with Al-E75A small interfering RNA. The rates of egg incubation rates were considerably lower in the RNA interference-treated animals compared to the untreated controls. In order to investigate the molecular mechanism underlying the effects described above, vitellogenin (Al-Vg) was selected for further investigation. The expression pattern of Al-Vg was similar to that of Al-E75A and was up-regulated by 20E. After knockdown of Al-E75A, the expression profile of Al-Vg and the protein levels were down-regulated. These findings suggest that Al-E75A plays a crucial role in the regulation of Al-Vg expression in Ap. lucorum. © 2017 The Royal Entomological Society.
Ophthalmic branch radiofrequency thermocoagulation for atypical trigeminal neuralgia:a case report.
Du, Shibin; Ma, Xiaoliang; Li, Xiaoqin; Yuan, Hongjie
2015-01-01
Trigeminal neuralgia is an intense neuralgia involving facial areas supplied by trigeminal nerve. The pain is characterized by sudden onset, short persistence, sharp or lancinating. Trigeminal neuralgia commonly affects frontal areas, infraorbital or paranasal areas, mandibular areas and teeth. While Trigeminal neuralgia affecting merely the upper eyelid is rare. Here we report a case of atypical Trigeminal neuralgia confined to the upper eyelid. The patient was pain free during the follow-up period of 6 months after unusual ophthalmic branch radiofrequency thermocoagulation. A 55-year-old female patient was diagnosed as primary trigeminal neuralgia involving the right upper eyelid. As the pain could not be controlled by drug therapy, peripheral nerve branch radiofrequency thermocoagulation was recommended. A combination of infratrochlear, supratrochlear and lacrimal radiofrequency thermocoagulation was implemented in this case. The point where the bridge of the nose abuts the supraorbital ridge and the point slightly above the lateral canthus along outer border of the orbit were selected respectively as the puncture sites. After positive diagnostic test, radiofrequency thermocoagulation of the above-mentioned nerve branches was performed respectively. The patient was pain free immediately after the treatment and during the follow-up period of 6 months. Trigeminal neuralgia is a common severe and chronic facial neuralgia which requires accurate diagnosis and effective therapy. With typical clinical symptoms, normal neurological signs, normal CT and MRI findings, the patient was diagnosed as classic trigeminal neuralgia. As the patient was drug resistant, some invasive treatments were considered. Peripheral branch neurolysis was chosen for its minimal invasiveness, convenience, low risk and not affecting further invasive treatments. According to the anatomic data and the diagnostic test results, infratrochlear, supratrochlear and lacrimal nerve were responsible, therefore, an unusual combination of infratrochlear, supratrochlear, and lacrimal radiofrequency thermocoagulation was implemented for this patient. Radiofrequency thermocoagulation is an effective treatment option for trigeminal neuralgia. Peripheral branch radiofrequency thermocoagulation for trigeminal neuralgia should be considered preferentially due to its minimal invasiveness and convenience. Furthermore, as the sensory innervation of the upper eyelid is complex, the knowledge of peripheral distribution of trigeminal nerve is essential.
Method of and apparatus for modeling interactions
Budge, Kent G.
2004-01-13
A method and apparatus for modeling interactions can accurately model tribological and other properties and accommodate topological disruptions. Two portions of a problem space are represented, a first with a Lagrangian mesh and a second with an ALE mesh. The ALE and Lagrangian meshes are constructed so that each node on the surface of the Lagrangian mesh is in a known correspondence with adjacent nodes in the ALE mesh. The interaction can be predicted for a time interval. Material flow within the ALE mesh can accurately model complex interactions such as bifurcation. After prediction, nodes in the ALE mesh in correspondence with nodes on the surface of the Lagrangian mesh can be mapped so that they are once again adjacent to their corresponding Lagrangian mesh nodes. The ALE mesh can then be smoothed to reduce mesh distortion that might reduce the accuracy or efficiency of subsequent prediction steps. The process, from prediction through mapping and smoothing, can be repeated until a terminal condition is reached.
Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia
Imboden, Hans; Patil, Jaspal; Nussberger, Juerg; Nicoud, Françoise; Hess, Benno; Ahmed, Nermin; Schaffner, Thomas; Wellner, Maren; Müller, Dominik; Inagami, Tadashi; Senbonmatsu, Takaaki; Pavel, Jaroslav; Saavedra, Juan M.
2009-01-01
To clarify the role of Angiotensin II (Ang II) in the sensory system and especially in the trigeminal ganglia, we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of Ang II and substance P in the rat and human trigeminal ganglia. The rat trigeminal ganglia expressed substantial amounts of Ang-N- and ACE mRNA as determined by quantitative real time PCR. Renin mRNA was untraceable in rat samples. Cathepsin D was detected in the rat trigeminal ganglia indicating the possibility of existence of pathways alternative to renin for Ang I formation. In situ hybridization in rat trigeminal ganglia revealed expression of Ang-N mRNA in the cytoplasm of numerous neurons. By using immunocytochemistry, a number of neurons and their processes in both the rat and human trigeminal ganglia were stained for Ang II. Post in situ hybridization immunocytochemistry reveals that in the rat trigeminal ganglia some, but not all Ang-N mRNA-positive neurons marked for Ang II. In some neurons Substance P was found colocalized with Ang II. Angiotensins from rat trigeminal ganglia were quantitated by radioimmunoassay with and without prior separation by high performance liquid chromatography. Immunoreactive angiotensin II (ir-Ang II) was consistently present and the sum of true Ang II (1-8) octapeptide and its specifically measured metabolites were found to account for it. Radioimmunological and immunocytochemical evidence of ir-Ang II in neuronal tissue is compatible with Ang II as a neurotransmitter. In conclusion, these results suggest that Ang II could be produced locally in the neurons of rat trigeminal ganglia. The localization and colocalization of neuronal Ang II with Substance P in the trigeminal ganglia neurons may be the basis for a participation and function of Ang II in the regulation of nociception and migraine pathology. PMID:19323983
The big CGRP flood - sources, sinks and signalling sites in the trigeminovascular system.
Messlinger, Karl
2018-03-12
Calcitonin gene-related peptide (CGRP) has long been a focus of migraine research, since it turned out that inhibition of CGRP or CGRP receptors by antagonists or monoclonal IgG antibodies was therapeutic in frequent and chronic migraine. This contribution deals with the questions, from which sites CGRP is released, where it is drained and where it acts to cause its headache proliferating effects in the trigeminovascular system. The available literature suggests that the bulk of CGRP is released from trigeminal afferents both in meningeal tissues and at the first synapse in the spinal trigeminal nucleus. CGRP may be drained off into three different compartments, the venous blood plasma, the cerebrospinal fluid and possibly the glymphatic system. CGRP receptors in peripheral tissues are located on arterial vessel walls, mononuclear immune cells and possibly Schwann cells; within the trigeminal ganglion they are located on neurons and glial cells; in the spinal trigeminal nucleus they can be found on central terminals of trigeminal afferents. All these structures are potential signalling sites for CGRP, where CGRP mediates arterial vasodilatation but not direct activation of trigeminal afferents. In the spinal trigeminal nucleus a facilitating effect on synaptic transmission seems likely. In the trigeminal ganglion CGRP is thought to initiate long-term changes including cross-signalling between neurons and glial cells based on gene expression. In this way, CGRP may upregulate the production of receptor proteins and pro-nociceptive molecules. CGRP and other big molecules cannot easily pass the blood-brain barrier. These molecules may act in the trigeminal ganglion to influence the production of pronociceptive substances and receptors, which are transported along the central terminals into the spinal trigeminal nucleus. In this way peripherally acting therapeutics can have a central antinociceptive effect.
Chakraborty, Tridib; Bhuniya, Dipak; Chatterjee, Mary; Rahaman, Mosiur; Singha, Dipak; Chatterjee, Baidya Nath; Datta, Subrata; Rana, Ajay; Samanta, Kartick; Srivastawa, Sunil; Maitra, Sankar K; Chatterjee, Malay
2007-12-28
To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)-bearing murine model. Male Swiss albino mice were divided into four groups: Group A was the untreated normal control; Group B was the EAC control mice group that received serial, intraperitoneal (ip) inoculations of rapidly proliferating 2 x 10(5) viable EAC cells in 0.2 mL of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract (ALE) of the plant at a dose of 2.5 mg/kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tumour inoculation (ALE control); and Group D was the EAC + ALE-treatment group. The chemopreventive potential of the ALE was evaluated in a murine model by studying various biological parameters and genotoxic markers, such as tumour cell count, mean survival of the animals, haematological indices, hepatocellular histology, immunohistochemical expression of liver metallothionein (MT) protein, sister-chromatid exchanges (SCEs), and DNA alterations. Treatment of the EAC-bearing mice with the ALE significantly (P < 0.001) reduced viable tumour cell count by 68.34% (228.7 x 10(6) +/- 0.53) when compared to EAC control mice (72.4 x 10(6) +/- 0.49), and restored body and organ weights almost to the normal values. ALE administration also increased (P < 0.001) mean survival of the hosts from 35 +/- 3.46 d in EAC control mice to 83 +/- 2.69 d in EAC + ALE-treated mice. Haematological indices also showed marked improvement with administration of ALE in EAC-bearing animals. There was a significant increase in RBC count (P < 0.001), hemoglobin percent (P < 0.001), and haematocrit value (P < 0.001) from 4.3 +/- 0.12, 6.4 +/- 0.93, and 17.63 +/- 0.72 respectively in EAC control mice to 7.1 +/- 0.13, 12.1 +/- 0.77, and 30.23 +/- 0.57 respectively in EAC + ALE-treated group, along with concurrent decrement (P < 0.001) in WBC count from 18.8 +/- 0.54 in EAC control to 8.4 +/- 0.71 in EAC + ALE. Furthermore, treatment with ALE substantially improved hepatocellular architecture and no noticeable neoplastic lesions or foci of cellular alteration were observed. Daily administration of the ALE was found to limit liver MT expression, an important marker of cell proliferation with concomitant reduction in MT immunoreactivity (62.25 +/- 2.58 vs 86.24 +/- 5.69, P < 0.01). ALE was also potentially effective in reducing (P < 0.001) the frequency of SCEs from 14.94 +/- 2.14 in EAC control to 5.12 +/- 1.16 in EAC + ALE-treated group. Finally, in comparison to the EAC control, ALE was able to suppress in vivo DNA damage by abating the generations of 'tailed' DNA by 53.59% (98.65 +/- 2.31 vs 45.06 +/- 1.14, P < 0.001), and DNA single-strand breaks (SSBs) by 38.53% (3.14 +/- 0.31 vs 1.93 +/- 0.23, P < 0.01) in EAC-bearing murine liver. Our data indicate that, ALE is beneficial in restoring haematological and hepatic histological profiles and in lengthening the survival of the animals against the proliferation of ascites tumour in vivo. Finally, the chemopreventive efficacy of the ALE is manifested in limiting MT expression and in preventing DNA alterations in murine liver. The promising results of this study suggest further investigation into the chemopreventive mechanisms of the medicinal plant A. ilicifolius in vivo and in vitro.
Active Learning in Engineering Education: A (Re)Introduction
ERIC Educational Resources Information Center
Lima, Rui M.; Andersson, Pernille Hammar; Saalman, Elisabeth
2017-01-01
The informal network "Active Learning in Engineering Education" (ALE) has been promoting Active Learning since 2001. ALE creates opportunity for practitioners and researchers of engineering education to collaboratively learn how to foster learning of engineering students. The activities in ALE are centred on the vision that learners…
Activation of oral trigeminal neurons by fatty acids is dependent upon intracellular calcium.
Yu, Tian; Shah, Bhavik P; Hansen, Dane R; Park-York, MieJung; Gilbertson, Timothy A
2012-08-01
The chemoreception of dietary fat in the oral cavity has largely been attributed to activation of the somatosensory system that conveys the textural properties of fat. However, the ability of fatty acids, which are believed to represent the proximate stimulus for fat taste, to stimulate rat trigeminal neurons has remained unexplored. Here, we found that several free fatty acids are capable of activating trigeminal neurons with different kinetics. Further, a polyunsaturated fatty acid, linoleic acid (LA), activates trigeminal neurons by increasing intracellular calcium concentration and generating depolarizing receptor potentials. Ion substitution and pharmacological approaches reveal that intracellular calcium store depletion is crucial for LA-induced signaling in a subset of trigeminal neurons. Using pseudorabies virus (PrV) as a live cell tracer, we identified a subset of lingual nerve-innervated trigeminal neurons that respond to different subsets of fatty acids. Quantitative real-time PCR of several transient receptor potential channel markers in individual neurons validated that PrV labeled a subset but not the entire population of lingual-innervated trigeminal neurons. We further confirmed that the LA-induced intracellular calcium rise is exclusively coming from the release of calcium stores from the endoplasmic reticulum in this subset of lingual nerve-innervated trigeminal neurons.
Activation of Oral Trigeminal Neurons by Fatty Acids is Dependent upon Intracellular Calcium
Yu, Tian; Shah, Bhavik P.; Hansen, Dane R.; Park-York, MieJung; Gilbertson, Timothy A.
2012-01-01
The chemoreception of dietary fat in the oral cavity has largely been attributed to activation of the somatosensory system that conveys the textural properties of fat. However, the ability of fatty acids, which are believed to represent the proximate stimulus for fat taste, to stimulate rat trigeminal neurons has remained unexplored. Here, we found that several free fatty acids are capable of activating trigeminal neurons with different kinetics. Further, a polyunsaturated fatty acid, linoleic acid (LA), activates trigeminal neurons by increasing intracellular calcium concentration and generating depolarizing receptor potentials. Ion substitution and pharmacological approaches reveal that intracellular calcium store depletion is crucial for LA-induced signaling in a subset of trigeminal neurons. Using pseudorabies virus (PrV) as a live cell tracer, we identified a subset of lingual nerve-innervated trigeminal neurons that respond to different subsets of fatty acids. Quantitative real-time PCR of several transient receptor potential (TRP) channel markers in individual neurons validated that PrV labeled a subset but not the entire population of lingual-innervated trigeminal neurons. We further confirmed that the LA-induced intracellular calcium rise is exclusively coming from the release of calcium stores from the endoplasmic reticulum in this subset of lingual nerve-innervated trigeminal neurons. PMID:22644615
Chemosensory Information Processing between Keratinocytes and Trigeminal Neurons
Sondersorg, Anna Christina; Busse, Daniela; Kyereme, Jessica; Rothermel, Markus; Neufang, Gitta; Gisselmann, Günter; Hatt, Hanns; Conrad, Heike
2014-01-01
Trigeminal fibers terminate within the facial mucosa and skin and transmit tactile, proprioceptive, chemical, and nociceptive sensations. Trigeminal sensations can arise from the direct stimulation of intraepithelial free nerve endings or indirectly through information transmission from adjacent cells at the peripheral innervation area. For mechanical and thermal cues, communication processes between skin cells and somatosensory neurons have already been suggested. High concentrations of most odors typically provoke trigeminal sensations in vivo but surprisingly fail to activate trigeminal neuron monocultures. This fact favors the hypothesis that epithelial cells may participate in chemodetection and subsequently transmit signals to neighboring trigeminal fibers. Keratinocytes, the major cell type of the epidermis, express various receptors that enable reactions to multiple environmental stimuli. Here, using a co-culture approach, we show for the first time that exposure to the odorant chemicals induces a chemical communication between human HaCaT keratinocytes and mouse trigeminal neurons. Moreover, a supernatant analysis of stimulated keratinocytes and subsequent blocking experiments with pyrodoxalphosphate-6-azophenyl-2′,4′-disulfonate revealed that ATP serves as the mediating transmitter molecule released from skin cells after odor stimulation. We show that the ATP release resulting from Javanol® stimulation of keratinocytes was mediated by pannexins. Consequently, keratinocytes act as chemosensors linking the environment and the trigeminal system via ATP signaling. PMID:24790106
ALES: An Innovative Argument-Learning Environment
ERIC Educational Resources Information Center
Abbas, Safia; Sawamura, Hajime
2010-01-01
This paper presents the development of an Argument-Learning System (ALES). The idea is based on the AIF (argumentation interchange format) ontology using "Walton theory". ALES uses different mining techniques to manage a highly structured arguments repository. This repository was designed, developed and implemented by the authors. The aim is to…
Application of the ALE and MBE Methods to the Growth of Layered Hg sub x Cd sub 1-x Te Films.
1986-09-26
films / We have studied the applicability of the Atomic Layer Epitaxy (ALE, vee Ref. -1pand Molecular Beam Epitaxy (MBE) ito growth of Hg2 Cdi- ,Te...thin- films throughout the composition range 0 x $ 0.8. The progress of the Contract has been reported periodically in five interim reports. This final...I separate sources) yielded films with high x values. On the grounds of these observations we do not find ALE suitable for growth of HgCdTe. 2) ALE
Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration
Finger, Thomas E.; Böttger, Bärbel; Hansen, Anne; Anderson, Karl T.; Alimohammadi, Hessamedin; Silver, Wayne L.
2003-01-01
Inhalation of irritating substances leads to activation of the trigeminal nerve, triggering protective reflexes that include apnea or sneezing. Receptors for trigeminal irritants are generally assumed to be located exclusively on free nerve endings within the nasal epithelium, requiring that trigeminal irritants diffuse through the junctional barrier at the epithelial surface to activate receptors. We find, in both rats and mice, an extensive population of chemosensory cells that reach the surface of the nasal epithelium and form synaptic contacts with trigeminal afferent nerve fibers. These chemosensory cells express T2R “bitter-taste” receptors and α-gustducin, a G protein involved in chemosensory transduction. Functional studies indicate that bitter substances applied to the nasal epithelium activate the trigeminal nerve and evoke changes in respiratory rate. By extending to the surface of the nasal epithelium, these chemosensory cells serve to expand the repertoire of compounds that can activate trigeminal protective reflexes. The trigeminal chemoreceptor cells are likely to be remnants of the phylogenetically ancient population of solitary chemoreceptor cells found in the epithelium of all anamniote aquatic vertebrates. PMID:12857948
Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration.
Finger, Thomas E; Böttger, Bärbel; Hansen, Anne; Anderson, Karl T; Alimohammadi, Hessamedin; Silver, Wayne L
2003-07-22
Inhalation of irritating substances leads to activation of the trigeminal nerve, triggering protective reflexes that include apnea or sneezing. Receptors for trigeminal irritants are generally assumed to be located exclusively on free nerve endings within the nasal epithelium, requiring that trigeminal irritants diffuse through the junctional barrier at the epithelial surface to activate receptors. We find, in both rats and mice, an extensive population of chemosensory cells that reach the surface of the nasal epithelium and form synaptic contacts with trigeminal afferent nerve fibers. These chemosensory cells express T2R "bitter-taste" receptors and alpha-gustducin, a G protein involved in chemosensory transduction. Functional studies indicate that bitter substances applied to the nasal epithelium activate the trigeminal nerve and evoke changes in respiratory rate. By extending to the surface of the nasal epithelium, these chemosensory cells serve to expand the repertoire of compounds that can activate trigeminal protective reflexes. The trigeminal chemoreceptor cells are likely to be remnants of the phylogenetically ancient population of solitary chemoreceptor cells found in the epithelium of all anamniote aquatic vertebrates.
Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E
1978-01-01
The main aim of the present study was to localize with electrophysiological techniques the central projections and terminations of the aberrant trigeminal fibres contained in the oculomotor nerve of the lamb. After severing a trigeminal root, single-shock electrical stimulation of the trigeminal axons present in the central stump of the ipsilateral oculomotor nerve evoked field potentials in the area of, i) the subnucleus gelatinosus of the nucleus caudalis trigemini at the level of C1-C2; ii) the main sensory trigeminal nucleus; iii) the descending trigeminal nucleus and tract; iv) the adjacent reticular formation. Units whose discharge rate was influenced by such a stimulation were also found in the same territories. These regions actually exhibited degenerations after cutting an oculomotor nerve. We conclude, therefore, that the trigeminal fibres which leave the Vth nerve at the level of the cavernous sinus and enter the brain stem through the IIIrd nerve, end in the same structures which receive the terminations of the afferent fibres entering the brain stem through the sensory trigeminal root.
Huang, Fang; He, Hongwen; Fan, Wenguo; Liu, Yongliang; Zhou, Hongyu; Cheng, Bin
2013-01-01
Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin receptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histochemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings suggest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin's regulatory effect on pain is attenuated. PMID:25206619
Chen, Guo-Xian; Zheng, Shuai; Qin, Shuai; Zhong, Zhao-Ming; Wu, Xiu-Hua; Huang, Zhi-Ping; Li, Wei; Ding, Ruo-Ting; Yu, Hui; Chen, Jian-Ting
2014-01-01
Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats. A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45-55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis. Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher Fmax compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups. Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture.
Zhong, Zhao-Ming; Wu, Xiu-Hua; Huang, Zhi-Ping; Li, Wei; Ding, Ruo-Ting; Yu, Hui; Chen, Jian-Ting
2014-01-01
Background Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats. Methods A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45–55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis. Results Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher Fmax compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups. Conclusions Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture. PMID:24796785
Gospodarev, Vadim; Chakravarthy, Vikram; Harms, Casey; Myers, Hannah; Kaplan, Brett; Kim, Esther; Pond, Matthew; De Los Reyes, Kenneth
2018-05-01
Trigeminal neuralgia (TGN) causes severe unilateral facial pain. The etiology is hypothesized to be segmental demyelination of the trigeminal nerve root via compression by the superior cerebellar artery (SCA). Microvascular decompression (MVD) allows immediate and long-term pain relief. Preoperative evaluation includes magnetic resonance imaging (MRI) and/or magnetic resonance angiography of the brain. Having a pacemaker is a contraindication for MRI. There have been isolated reports of using computed tomography (CT) cisternography scans for radiation planning for TGN. A 75-year-old male with a permanent pacemaker who had refractory TGN in the V2 (maxillary) distribution of the trigeminal nerve underwent CT cisternography to prepare for MVD. CT angiography with Isovue 370 intravenous contrast injection and 0.625-mm axial images were obtained from the skull base across the posterior fossa. An intrathecal injection of Isovue 180 was performed at the L2/3 level. Imaging revealed the right SCA abutting the medial margin of the proximal right trigeminal nerve. In surgery (K.D.), a standard retrosigmoid suboccipital craniotomy was performed to access the cerebellopontine angle and separate the abutting SCA and trigeminal nerve. The patient had immediate pain relief. MRI is the preferred method of evaluating for TGN because it offers excellent visualization of vasculature in relation to the trigeminal nerve without accompanying radiation exposure. However, for patients who have contraindications to MRI, CT cisternography is shown to also be an effective method for visualizing the trigeminal root entry zone and nearby vasculature in preparation for MVD of the trigeminal nerve. Published by Elsevier Inc.
Taylor, Olivia; Barrett, Robert D; McLellan, Tracey; McKinlay, Audrey
2015-01-01
To investigate whether individuals with a history of traumatic brain injury (TBI) experience a greater number of adverse life events (ALE) compared to controls, to identify significant predictors of experiencing ALE and whether the severity of childhood TBI negatively influences adult life outcomes. A total of 167 individuals, injured prior to age 18, 5 or more years post-injury and 18 or more years of age, were recruited in the Canterbury region of New Zealand, with 124 having sustained childhood TBI (62 mild, 62 moderate/severe) and 43 orthopaedic injury controls. Participants were asked about ALE they had experienced and other adult life outcomes. Individuals with a history of TBI experienced more ALE compared to controls. The number of ALE experienced by an individual was associated with more visits to the doctor, lower education level and lower satisfaction with material standard of living. Childhood TBI is associated with an increased number of ALE and adult negative life outcomes. Understanding factors that contribute to negative outcomes following childhood TBI will provide an avenue for rehabilitation and support to reduce any problems in adulthood.
Moukit, Mounir; Fadel, Fatimazahra Ait El; Kouach, Jaouad; Babahabib, Abdellah; Dehayni, Mohammed; Rahali, Driss Moussaoui
2016-01-01
La tuberculose est une maladie infectieuse curable qui peut simuler dans sa localisation péritonéale un cancer ovarien avancé conduisant ainsi à une chirurgie étendue et inutile souvent chez des femmes en âge de reproduction. Nous rapportons un nouveau cas de tuberculose péritonéale pseudo tumorale chez une patiente âgée de 43 ans chez qui le diagnostic d’un cancer ovarien avec carcinose péritonéale avait été suspecté. La laparotomie exploratrice avec examen histologique extemporané ont permis de confirmer le diagnostic de tuberculose péritonéale. La patiente a bien répondu au traitement antituberculeux selon le protocole 2ERHZ/4RH. PMID:28292155
Renton, Tara
2011-01-01
This article provides a simple overview of acute trigeminal pain for the non dentist. This article does not cover oral mucosal diseases (vesiculobullous disorders) that may cause acute pain. Dental pain is the most common in this group and it can present in several different ways. Of particular interest for is that dental pain can mimic both trigeminal neuralgia and other chronic trigeminal pain disorders. It is crucial to exclude these disorders whilst managing patients with chronic trigeminal pain. PMID:26527224
Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.
Mizera, L; Gossrau, G; Hummel, T; Haehner, A
2017-01-01
There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without intake of analgesics. Non-opioid and opioid drugs did not differ in their effects on chemosensory function. © 2016 European Pain Federation - EFIC®.
Chatchaisak, Duangthip; Connor, Mark; Srikiatkhachorn, Anan; Chetsawang, Banthit
2018-05-01
Growing evidence suggests that calcitonin gene-related peptide (CGRP) participates in trigeminal nociceptive responses. However, the role of CGRP in sensitization or desensitization of nociceptive transduction remains poorly understood. In this study, we sought to further investigate the CGRP-induced up-regulation of transient receptor potential vanilloid-1 (TRPV1) and the responses of trigeminal neurons to nociceptive stimuli. Rat trigeminal ganglion (TG) organ cultures and isolated trigeminal neurons were incubated with CGRP. An increase in TRPV1 levels was observed in CGRP-incubated TG organ cultures. CGRP potentiated capsaicin-induced increase in phosphorylated CaMKII levels in the TG organ cultures. The incubation of the trigeminal neurons with CGRP significantly increased the inward currents in response to capsaicin challenge, and this effect was inhibited by co-incubation with the CGRP receptor antagonist, BIBN4068BS or the inhibitor of protein kinase A, H-89. These findings reveal that CGRP acting on trigeminal neurons may play a significant role in facilitating cellular events that contribute to the peripheral sensitization of the TG in nociceptive transmission.
TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor
Chen, Yong; Kanju, Patrick; Fang, Quan; Lee, Suk Hee; Parekh, Puja K.; Lee, Whasil; Moore, Carlene; Brenner, Daniel; Gereau, Robert W.; Wang, Fan; Liedtke, Wolfgang
2014-01-01
Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin-model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many anti-pain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally-innervated territories in mice. Also, we have examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior, because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, also because we have recently defined TRPV4’s role in response to air-borne irritants, and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whiskerpad injections. This conclusion is supported by studies with Trpv4−/− mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca++. Using TRPA1-blocker and Trpa1−/− mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, TMJ, facial and dental pain, and irritation of trigeminally-innervated surface epithelia. PMID:25281928
Ashwell, Ken W S; Hardman, Craig D; Giere, Peter
2012-01-01
The extant monotremes (platypus and echidnas) are believed to all be capable of electroreception in the trigeminal pathways, although they differ significantly in the number and distribution of electroreceptors. It has been argued by some authors that electroreception was first developed in an aquatic environment and that echidnas are descended from a platypus-like ancestor that invaded an available terrestrial habitat. If this were the case, one would expect the developmental trajectories of the trigeminal pathways to be similar in the early stages of platypus and short-beaked echidna development, with structural divergence occurring later. We examined the development of the peripheral trigeminal pathway from snout skin to trigeminal ganglion in sectioned material in the Hill and Hubrecht collections to test for similarities and differences between the two during the development from egg to adulthood. Each monotreme showed a characteristic and different pattern of distribution of developing epidermal sensory gland specializations (electroreceptor primordia) from the time of hatching. The cross-sectional areas of the trigeminal divisions and the volume of the trigeminal ganglion itself were also very different between the two species at embryonic ages, and remained consistently different throughout post-hatching development. Our findings indicate that the trigeminal pathways in the short-beaked echidna and the platypus follow very different developmental trajectories from the earliest ages. These findings are more consistent with the notion that the platypus and echidna have both diverged from an ancestor with rudimentary electroreception and/or trigeminal specialization, rather than the contention that the echidna is derived from a platypus-like ancestor. Copyright © 2011 S. Karger AG, Basel.
Franceschini, Alessia; Vilotti, Sandra; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Nistri, Andrea; Fabbretti, Elsa
2013-01-01
Latent changes in trigeminal ganglion structure and function resembling inflammatory conditions may predispose to acute attacks of migraine pain. Here, we investigated whether, in trigeminal sensory ganglia, cytokines such as TNFα might contribute to a local inflammatory phenotype of a transgenic knock-in (KI) mouse model of familial hemiplegic migraine type-1 (FHM-1). To this end, macrophage occurrence and cytokine expression in trigeminal ganglia were compared between wild type (WT) and R192Q mutant CaV2.1 Ca2+ channel (R192Q KI) mice, a genetic model of FHM-1. Cellular and molecular characterization was performed using a combination of confocal immunohistochemistry and cytokine assays. With respect to WT, R192Q KI trigeminal ganglia were enriched in activated macrophages as suggested by their morphology and immunoreactivity to the markers Iba1, CD11b, and ED1. R192Q KI trigeminal ganglia constitutively expressed higher mRNA levels of IL1β, IL6, IL10 and TNFα cytokines and the MCP-1 chemokine. Consistent with the report that TNFα is a major factor to sensitize trigeminal ganglia, we observed that, following an inflammatory reaction evoked by LPS injection, TNFα expression and macrophage occurrence were significantly higher in R192Q KI ganglia with respect to WT ganglia. Our data suggest that, in KI trigeminal ganglia, the complex cellular and molecular environment could support a new tissue phenotype compatible with a neuroinflammatory profile. We propose that, in FHM patients, this condition might contribute to trigeminal pain pathophysiology through release of soluble mediators, including TNFα, that may modulate the crosstalk between sensory neurons and resident glia, underlying the process of neuronal sensitisation. PMID:23326332
Schöbel, Nicole; Beltrán, Leopoldo; Wetzel, Christian Horst; Hatt, Hanns
2013-01-01
Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual’s physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants), environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants). In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia. PMID:24205061
Barreiro-Iglesias, Antón; Romaus-Sanjurjo, Daniel; Senra-Martínez, Pablo; Anadón, Ramón; Rodicio, María Celina
2011-01-01
Studies in lampreys have revealed interesting aspects of the evolution of the trigeminal system and the jaw. In the present study, we found a marker that distinguishes subpopulations of trigeminal motoneurons innervating two different kinds of oropharyngeal muscles. Immunofluorescence with an antibody against doublecortin (DCX; a neuron-specific phosphoprotein) enabled identification of the trigeminal motoneurons that innervate the velar musculature of larval and recently transformed sea lampreys. DCX-immunoreactive (-ir) motoneurons were observed in the rostro-lateral part of the trigeminal motor nucleus of these animals, but not in lampreys 1 month or more after metamorphosis. Combined double DCX/tubulin and serotonin/tubulin immunofluorescence and tract-tracing experiments with neurobiotin (NB) were also performed in larvae for further characterization of this system. Rich innervation by DCX-ir fibers was observed on the muscle fibers of the velum but not on the upper lip or lower lip muscles, which were innervated by tubulin-ir/DCX-negative fibers. No double-labelled DCX-ir motoneurons were observed in experiments in which the tracer NB was applied to the upper lip. Innervation of velar muscles by serotonergic fibers is also reported. The present results indicate that development of the trigeminal motoneurons innervating the velum differs from that of the trigeminal motoneurons innervating the lips, which is probably related to the dramatic regression of the velum during metamorphosis. The absence of data on a similar subsystem in the trigeminal motor nucleus of gnathostomes suggests that they may be lamprey-specific motoneurons. These results provide support for the "heterotopic theory" of jaw evolution and are inconsistent with the theories of a velar origin for the gnathostome jaw. © 2011 Wiley Periodicals, Inc.
[Pathophysiology and treatment of orofacial pain.
Shinoda, Masamichi; Noma, Noboru
"Pain" is one of body defense mechanisms and crucial for the life support. However, orofacial pain such as myofascial pain syndrome, burning mouth syndrome and trigeminal neuralgia plays no part in body defense mechanisms and requires therapeutic intervention. Recent studies have indicated that plastic changes in the activities of trigeminal neurons, satellite glial cells in trigeminal ganglion, secondary neurons, microglia and astrocytes in trigeminal spinal subnucleus following orofacial inflammation and trigeminal nerve injury are responsible for orofacial pain mechanisms. Clinically, it is well known that the etiologic differential diagnosis which consists of careful history-taking and physical examination is essential for therapeutic decision in patients with orofacial pain. This report outlines the current knowledge on the pathophysiology, diagnosis, treatment of orofacial pain.
Differences in effectiveness of the active living every day program for older adults with arthritis.
Sperber, Nina R; Allen, Kelli D; Devellis, Brenda M; Devellis, Robert F; Lewis, Megan A; Callahan, Leigh F
2013-10-01
The authors explored whether demographic and psychosocial variables predicted differences in physical activity for participants with arthritis in a trial of Active Living Every Day (ALED). Participants (N = 280) from 17 community sites were randomized into ALED or usual care. The authors assessed participant demographic characteristics, self-efficacy, outcome expectations, pain, fatigue, and depressive symptoms at baseline and physical activity frequency at 20-wk follow-up. They conducted linear regression with interaction terms (Baseline Characteristic × Randomization Group). Being female (p ≤ .05), less depressed (p ≤ .05), or younger (p ≤ .10) was associated with more frequent posttest physical activity for ALED participants than for those with usual care. Higher education was associated with more physical activity for both ALED and usual-care groups. ALED was particularly effective for female, younger, and less depressed participants. Further research should determine whether modifications could produce better outcomes in other subgroups.
Do you see what I see? Optical morphology and visual capability of ‘disco’ clams (Ctenoides ales)
Dubielzig, Richard R.; Schobert, Charles S.; Teixeira, Leandro B.; Li, Jingchun
2017-01-01
ABSTRACT The ‘disco’ clam Ctenoides ales (Finlay, 1927) is a marine bivalve that has a unique, vivid flashing display that is a result of light scattering by silica nanospheres and rapid mantle movement. The eyes of C. ales were examined to determine their visual capabilities and whether the clams can see the flashing of conspecifics. Similar to the congener C. scaber, C. ales exhibits an off-response (shadow reflex) and an on-response (light reflex). In field observations, a shadow caused a significant increase in flash rate from a mean of 3.9 Hz to 4.7 Hz (P=0.0016). In laboratory trials, a looming stimulus, which increased light intensity, caused a significant increase in flash rate from a median of 1.8 Hz to 2.2 Hz (P=0.0001). Morphological analysis of the eyes of C. ales revealed coarsely-packed photoreceptors lacking sophisticated structure, resulting in visual resolution that is likely too low to detect the flashing of conspecifics. As the eyes of C. ales are incapable of perceiving conspecific flashing, it is likely that their vision is instead used to detect predators. PMID:28396488
Malhotra, Rahul; Chan, Angelique; Ajay, Shweta; Ma, Stefan; Saito, Yasuhiko
2016-10-01
To assess variation in gender gap (female-male) in inactive life expectancy (IALE) and active life expectancy (ALE) by definition of inactivity. Inactivity, among older Singaporeans, was defined as follows: Scenario 1-health-related difficulty in activities of daily living (ADLs); Scenario 2-health-related difficulty in ADLs/instrumental ADLs (IADLs); Scenario 3-health-related difficulty in ADLs/IADLs or non-health-related non-performance of IADLs. Multistate life tables computed IALE and ALE at age 60, testing three hypotheses: In all scenarios, life expectancy, absolute and relative IALE, and absolute ALE are higher for females (Hypothesis 1 [H1]); gender gap in absolute and relative IALE expands, and in absolute ALE, it contracts in Scenario 2 versus 1 (Hypothesis 2 [H2]); gender gap in absolute and relative IALE decreases, and in absolute ALE, it increases in Scenario 3 versus 2 (Hypothesis 3 [H3]). H1 was supported in Scenarios 1 and 3 but not Scenario 2. Both H2 and H3 were supported. Definition of inactivity influences gender gap in IALE and ALE. © The Author(s) 2016.
Ali, Khursheed; Dwivedi, Sourabh; Azam, Ameer; Saquib, Quaiser; Al-Said, Mansour S; Alkhedhairy, Abdulaziz A; Musarrat, Javed
2016-06-15
ZnO nanoparticles (ZnONPs) were synthesised through a simple and efficient biogenic synthesis approach, exploiting the reducing and capping potential of Aloe barbadensis Miller (A. vera) leaf extract (ALE). ALE-capped ZnO nanoparticles (ALE-ZnONPs) were characterized using UV-Vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) analyses. XRD analysis provided the average size of ZnONPs as 15 nm. FTIR spectral analysis suggested the role of phenolic compounds, terpenoids and proteins present in ALE, in nucleation and stability of ZnONPs. Flow cytometry and atomic absorption spectrophotometry (AAS) data analyses revealed the surface binding and internalization of ZnONPs in Gram +ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) cells, respectively. Significant antibacterial activity of ALE-ZnONPs was observed against extended spectrum beta lactamases (ESBL) positive E. coli, Pseudomonas aeruginosa, and methicillin resistant S. aureus (MRSA) clinical isolates exhibiting the MIC and MBC values of 2200, 2400 μg/ml and 2300, 2700 μg/ml, respectively. Substantial inhibitory effects of ALE-ZnONPs on bacterial growth kinetics, exopolysaccharides and biofilm formation, unequivocally suggested the antibiotic and anti-biofilm potential. Overall, the results elucidated a rapid, environmentally benign, cost-effective, and convenient method for ALE-ZnONPs synthesis, for possible applications as nanoantibiotics or drug carriers. Copyright © 2016 Elsevier Inc. All rights reserved.
Gamma Knife® radiosurgery for trigeminal neuralgia.
Yen, Chun-Po; Schlesinger, David; Sheehan, Jason P
2011-11-01
Trigeminal neuralgia is characterized by a temporary paroxysmal lancinating facial pain in the trigeminal nerve distribution. The prevalence is four to five per 100,000. Local pressure on nerve fibers from vascular loops results in painful afferent discharge from an injured segment of the fifth cranial nerve. Microvascular decompression addresses the underlying pathophysiology of the disease, making this treatment the gold standard for medically refractory trigeminal neuralgia. In patients who cannot tolerate a surgical procedure, those in whom a vascular etiology cannot be identified, or those unwilling to undergo an open surgery, stereotactic radiosurgery is an appropriate alternative. The majority of patients with typical facial pain will achieve relief following radiosurgical treatment. Long-term follow-up for recurrence as well as for radiation-induced complications is required in all patients undergoing stereotactic radiosurgery for trigeminal neuralgia.
Fried, Nathan T; Maxwell, Christina R; Elliott, Melanie B; Oshinsky, Michael L
2017-01-01
Background The blood-brain barrier (BBB) has been hypothesized to play a role in migraine since the late 1970s. Despite this, limited investigation of the BBB in migraine has been conducted. We used the inflammatory soup rat model of trigeminal allodynia, which closely mimics chronic migraine, to determine the impact of repeated dural inflammatory stimulation on BBB permeability. Methods The sodium fluorescein BBB permeability assay was used in multiple brain regions (trigeminal nucleus caudalis (TNC), periaqueductal grey, frontal cortex, sub-cortex, and cortex directly below the area of dural activation) during the episodic and chronic stages of repeated inflammatory dural stimulation. Glial activation was assessed in the TNC via GFAP and OX42 immunoreactivity. Minocycline was tested for its ability to prevent BBB disruption and trigeminal sensitivity. Results No astrocyte or microglial activation was found during the episodic stage, but BBB permeability and trigeminal sensitivity were increased. Astrocyte and microglial activation, BBB permeability, and trigeminal sensitivity were increased during the chronic stage. These changes were only found in the TNC. Minocycline treatment prevented BBB permeability modulation and trigeminal sensitivity during the episodic and chronic stages. Discussion Modulation of BBB permeability occurs centrally within the TNC following repeated dural inflammatory stimulation and may play a role in migraine. PMID:28457145
Li, Jin-Lian; Xiong, Kang-Hui; Dong, Yu-Lin; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru
2003-08-18
Vesicular glutamate transporters are responsible for glutamate transport into synaptic vesicles. In the present study, we examined immunohistochemically the expression of vesicular glutamate transporters, VGluT1 and VGluT2, in trigeminal ganglion neurons of the rat. Immunohistochemistry for VGluT1 and VGluT2 indicated that more than 80% of trigeminal ganglion neurons express VGluT1 and/or VGluT2 in their cell bodies. It also indicated that large and small trigeminal ganglion neurons express VGluT2 more frequently than VGluT1. Dual immunofluorescence histochemistry for VGluT1 and VGluT2 indicated that trigeminal ganglion neurons express VGluT2 more frequently than VGluT1 and that more than 80% of VGluT-expressing trigeminal ganglion neurons express VGluT1 and VGluT2. Many axon terminals in the superficial layers of the medullary dorsal horn also showed VGluT1 and VGluT2 immunoreactivities. Some of these axon terminals were confirmed to form the central core of the synaptic glomerulus. These results indicated that VGluT1 and VGluT2 are coexpressed in the cell bodies and axon terminals in most trigeminal ganglion neurons. Copyright 2003 Wiley-Liss, Inc.
Sumatriptan Inhibits TRPV1 Channels in Trigeminal Neurons
Evans, M. Steven; Cheng, Xiangying; Jeffry, Joseph A.; Disney, Kimberly E.; Premkumar, Louis S.
2011-01-01
Objective To understand a possible role for transient potential receptor vanilloid 1 (TRPV1) ion channels in sumatriptan relief of pain mediated by trigeminal nociceptors. Background TRPV1 channels are expressed in small nociceptive sensory neurons. In dorsal root ganglia (DRG), TRPV1-containing nociceptors mediate certain types of inflammatory pain. Neurogenic inflammation of cerebral dura and blood vessels in the trigeminal nociceptive system is thought to be important in migraine pain, but the ion channels important in transducing migraine pain are not known. Sumatriptan is an agent effective in treatment of migraine and cluster headache. We hypothesized that sumatriptan might modulate activity of TRPV1 channels found in the trigeminal nociceptive system. Methods We used immunohistochemistry to detect the presence of TRPV1 channel protein, whole cell recording in acutely dissociated trigeminal ganglia (TG) to detect functionality of TRPV1 channels, and whole cell recording in trigeminal nucleus caudalis (TNC) to detect effects on release of neurotransmitters from trigeminal neurons onto second order sensory neurons. Effects specifically on TG neurons that project to cerebral dura were assessed by labeling dural nociceptors with DiI. Results Immunohistochemistry demonstrated that TRPV1 channels are present in cerebral dura, trigeminal ganglion, and in the trigeminal nucleus caudalis. Capsaicin, a TRPV1 agonist, produced depolarization and repetitive action potential firing in current clamp recordings and large inward currents in voltage clamp recordings from acutely dissociated TG neurons, demonstrating that TRPV1 channels are functional in trigeminal neurons. Capsaicin increased spontaneous excitatory postsynaptic currents (sEPSCs) in neurons of layer II in TNC slices, showing that these channels have a physiological effect on central synaptic transmission. Sumatriptan (10 μM), a selective anti-migraine drug inhibited TRPV1-mediated inward currents in TG. and capsaicin-elicited sEPSCs in TNC slices. The same effects of capsaicin and sumatriptan were found in acutely dissociated DiI-labeled TG neurons innervating cerebral dura. Conclusion Our results build on previous work indicating that TRPV1 channels in trigeminal nociceptors play a role in craniofacial pain. Our findings that TRPV1 is inhibited by the specific antimigraine drug sumatriptan, and that TRPV1 channels are functional in neurons projecting to cerebral dura suggests a specific role for these channels in migraine or cluster headache. PMID:22289052
IL-1β Stimulates COX-2 Dependent PGE2 Synthesis and CGRP Release in Rat Trigeminal Ganglia Cells
Neeb, Lars; Hellen, Peter; Boehnke, Carsten; Hoffmann, Jan; Schuh-Hofer, Sigrid; Dirnagl, Ulrich; Reuter, Uwe
2011-01-01
Objective Pro-inflammatory cytokines like Interleukin-1 beta (IL-1β) have been implicated in the pathophysiology of migraine and inflammatory pain. The trigeminal ganglion and calcitonin gene-related peptide (CGRP) are crucial components in the pathophysiology of primary headaches. 5-HT1B/D receptor agonists, which reduce CGRP release, and cyclooxygenase (COX) inhibitors can abort trigeminally mediated pain. However, the cellular source of COX and the interplay between COX and CGRP within the trigeminal ganglion have not been clearly identified. Methods and Results 1. We used primary cultured rat trigeminal ganglia cells to assess whether IL-1β can induce the expression of COX-2 and which cells express COX-2. Stimulation with IL-1β caused a dose and time dependent induction of COX-2 but not COX-1 mRNA. Immunohistochemistry revealed expression of COX-2 protein in neuronal and glial cells. 2. Functional significance was demonstrated by prostaglandin E2 (PGE2) release 4 hours after stimulation with IL-1β, which could be aborted by a selective COX-2 (parecoxib) and a non-selective COX-inhibitor (indomethacin). 3. Induction of CGRP release, indicating functional neuronal activation, was seen 1 hour after PGE2 and 24 hours after IL-1β stimulation. Immunohistochemistry showed trigeminal neurons as the source of CGRP. IL-1β induced CGRP release was blocked by parecoxib and indomethacin, but the 5-HT1B/D receptor agonist sumatriptan had no effect. Conclusion We identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation. Activation of neuronal and glial cells in the trigeminal ganglion by IL-β leads to an elevated expression of COX-2 in these cells. Newly synthesized PGE2 (by COX-2) in turn activates trigeminal neurons to release CGRP. These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2 and CGRP. The results could help to explain the mechanism of action of COX-2 inhibitors in migraine. PMID:21394197
Clinical Evaluation of Targeting Accuracy of Gamma Knife Radiosurgery in Trigeminal Neuralgia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Massager, Nicolas; Abeloos, Laurence; Devriendt, Daniel
2007-12-01
Purpose: The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgical treatment with the Leksell Gamma Knife for trigeminal neuralgia. We also studied the applied radiation dose within the area of focal contrast enhancement on the trigeminal nerve root following radiosurgery. Methods and Materials: From an initial group of 78 patients with trigeminal neuralgia treated with gamma knife radiosurgery using a 90-Gy dose, we analyzed a subgroup of 65 patients for whom 6-month follow-up MRI showed focal contrast enhancement of the trigeminal nerve. Follow-up MRI was spatially coregistered to the radiosurgicalmore » planning MRI. Target accuracy was assessed from deviation of the coordinates of the intended target compared with the center of enhancement on postoperative MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was 0.91 mm in Euclidean space. The radiation doses fitting within the borders of the contrast enhancement of the trigeminal nerve root ranged from 49 to 85 Gy (median value, 77 {+-} 8.7 Gy). Conclusions: The median deviation found in clinical assessment of gamma knife treatment for trigeminal neuralgia is low and compatible with its high rate of efficiency. Focal enhancement of the trigeminal nerve after radiosurgery occurred in 83% of our patients and was not associated with clinical outcome. Focal enhancement borders along the nerve root fit with a median dose of 77 {+-} 8.7 Gy.« less
Simulating Small-Scale Experiments of In-Tunnel Airblast Using STUN and ALE3D
DOE Office of Scientific and Technical Information (OSTI.GOV)
Neuscamman, Stephanie; Glenn, Lewis; Schebler, Gregory
2011-09-12
This report details continuing validation efforts for the Sphere and Tunnel (STUN) and ALE3D codes. STUN has been validated previously for blast propagation through tunnels using several sets of experimental data with varying charge sizes and tunnel configurations, including the MARVEL nuclear driven shock tube experiment (Glenn, 2001). The DHS-funded STUNTool version is compared to experimental data and the LLNL ALE3D hydrocode. In this particular study, we compare the performance of the STUN and ALE3D codes in modeling an in-tunnel airblast to experimental results obtained by Lunderman and Ohrt in a series of small-scale high explosive experiments (1997).
Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn
2009-11-01
Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.
Magielse, Joanna; Verlaet, Annelies; Breynaert, Annelies; Keenoy, Begoña Manuel Y; Apers, Sandra; Pieters, Luc; Hermans, Nina
2014-01-01
The in vivo antioxidant activity of a quantified leaf extract of Cynara scolymus (artichoke) was studied. The aqueous artichoke leaf extract (ALE), containing 1.5% caffeoylquinic acid with chlorogenic acid being most abundant (0.30%), and luteolin-7-O-glucoside as major flavonoid (0.15%), was investigated by evaluating the effect on different oxidative stress biomarkers, after 3 wk oral supplementation in the streptozotocin-induced diabetic rat model. Apart from two test groups (0.2 g ALE/kg BW/day and 1 g ALE/kg BW/day, where BW is body weight), a healthy control group, untreated oxidative stress group, and vitamin E treated group (positive control) were included. A 0.2 g/kg BW/day of ALE decreased oxidative stress: malondialdehyde and 8-hydroxydeoxyguanosine levels significantly diminished, whereas erythrocyte glutathione levels significantly increased. A 1.0 g/kg BW/day ALE did not show higher antioxidant activity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Puri, Jyoti; Vinothini, Priya; Reuben, Jayne; Bellinger, Larry L.; Ailing, Li; Peng, Yuan B.; Kramer, Phillip R.
2012-01-01
Trigeminal ganglia neurons express the GABAA receptor subunit alpha 6 (Gabrα6) but the role of this particular subunit in orofacial hypersensitivity is unknown. In this report the function of Gabrα6 was tested by reducing its expression in the trigeminal ganglia and measuring the effect of this reduction on inflammatory temporomandibular joint (TMJ) hypersensitivity. Gabrα6 expression was reduced by infusing the trigeminal ganglia of male Sprague Dawley rats with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). Sixty hours after siRNA infusion the rats received a bilateral TMJ injection of complete Freund’s adjuvant to induce an inflammatory response. Hypersensitivity was then quantitated by measuring meal duration, which lengthens when hypersensitivity increases. Neuronal activity in the trigeminal ganglia was also measured by quantitating the amount of phosphorylated ERK. Rats in a different group that did not have TMJ inflammation had an electrode placed in the spinal cord at the level of C1 sixty hours after siRNA infusion to record extracellular electrical activity of neurons that responded to TMJ stimulation. Our results show that Gabrα6 was expressed in both neurons and satellite glia of the trigeminal ganglia and that Gabrα6 positive neurons within the trigeminal ganglia have afferents in the TMJ. Gabrα6 siRNA infusion reduced Gabrα6 gene expression by 30% and significantly lengthened meal duration in rats with TMJ inflammation. Gabrα6 siRNA infusion also significantly increased p-ERK expression in the trigeminal ganglia of rats with TMJ inflammation and increased electrical activity in the spinal cord of rats without TMJ inflammation. These results suggest that maintaining Gabrα6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception. PMID:22521829
NASA Astrophysics Data System (ADS)
Su, Xiaohui; Cao, Yuanwei; Zhao, Yong
2016-06-01
In this paper, an unstructured mesh Arbitrary Lagrangian-Eulerian (ALE) incompressible flow solver is developed to investigate the aerodynamics of insect hovering flight. The proposed finite-volume ALE Navier-Stokes solver is based on the artificial compressibility method (ACM) with a high-resolution method of characteristics-based scheme on unstructured grids. The present ALE model is validated and assessed through flow passing over an oscillating cylinder. Good agreements with experimental results and other numerical solutions are obtained, which demonstrates the accuracy and the capability of the present model. The lift generation mechanisms of 2D wing in hovering motion, including wake capture, delayed stall, rapid pitch, as well as clap and fling are then studied and illustrated using the current ALE model. Moreover, the optimized angular amplitude in symmetry model, 45°, is firstly reported in details using averaged lift and the energy power method. Besides, the lift generation of complete cyclic clap and fling motion, which is simulated by few researchers using the ALE method due to large deformation, is studied and clarified for the first time. The present ALE model is found to be a useful tool to investigate lift force generation mechanism for insect wing flight.
Overview and History of Trigeminal Neuralgia.
Patel, Smruti K; Liu, James K
2016-07-01
Although the symptoms associated with trigeminal neuralgia have been well documented, the root cause of this disease initially eluded most surgeons. Although early remedies were haphazard because of a lack of understanding about the condition, near the 20th century both medical and procedural therapies were established for the treatment of trigeminal neuralgia. These treatments include a variety of medications, chemoneurolysis, radiofrequency lesioning, percutaneous ablative procedures, stereotactic radiosurgery, and open rhizotomy and microvascular decompression. This report recounts the history of trigeminal neuralgia, from its earliest descriptions to the historical evolution of nonsurgical and surgical therapies. Copyright © 2016 Elsevier Inc. All rights reserved.
Johnson, Nicholas R; George, Steven M
2017-10-04
The thermal atomic layer etching (ALE) of WO 3 and W was demonstrated with new "conversion-fluorination" and "oxidation-conversion-fluorination" etching mechanisms. Both of these mechanisms are based on sequential, self-limiting reactions. WO 3 ALE was achieved by a "conversion-fluorination" mechanism using an AB exposure sequence with boron trichloride (BCl 3 ) and hydrogen fluoride (HF). BCl 3 converts the WO 3 surface to a B 2 O 3 layer while forming volatile WO x Cl y products. Subsequently, HF spontaneously etches the B 2 O 3 layer producing volatile BF 3 and H 2 O products. In situ spectroscopic ellipsometry (SE) studies determined that the BCl 3 and HF reactions were self-limiting versus exposure. The WO 3 ALE etch rates increased with temperature from 0.55 Å/cycle at 128 °C to 4.19 Å/cycle at 207 °C. W served as an etch stop because BCl 3 and HF could not etch the underlying W film. W ALE was performed using a three-step "oxidation-conversion-fluorination" mechanism. In this ABC exposure sequence, the W surface is first oxidized to a WO 3 layer using O 2 /O 3 . Subsequently, the WO 3 layer is etched with BCl 3 and HF. SE could simultaneously monitor the W and WO 3 thicknesses and conversion of W to WO 3 . SE measurements showed that the W film thickness decreased linearly with number of ABC reaction cycles. W ALE was shown to be self-limiting with respect to each reaction in the ABC process. The etch rate for W ALE was ∼2.5 Å/cycle at 207 °C. An oxide thickness of ∼20 Å remained after W ALE, but could be removed by sequential BCl 3 and HF exposures without affecting the W layer. These new etching mechanisms will enable the thermal ALE of a variety of additional metal materials including those that have volatile metal fluorides.
A Model for Designing Adaptive Laboratory Evolution Experiments.
LaCroix, Ryan A; Palsson, Bernhard O; Feist, Adam M
2017-04-15
The occurrence of mutations is a cornerstone of the evolutionary theory of adaptation, capitalizing on the rare chance that a mutation confers a fitness benefit. Natural selection is increasingly being leveraged in laboratory settings for industrial and basic science applications. Despite increasing deployment, there are no standardized procedures available for designing and performing adaptive laboratory evolution (ALE) experiments. Thus, there is a need to optimize the experimental design, specifically for determining when to consider an experiment complete and for balancing outcomes with available resources (i.e., laboratory supplies, personnel, and time). To design and to better understand ALE experiments, a simulator, ALEsim, was developed, validated, and applied to the optimization of ALE experiments. The effects of various passage sizes were experimentally determined and subsequently evaluated with ALEsim, to explain differences in experimental outcomes. Furthermore, a beneficial mutation rate of 10 -6.9 to 10 -8.4 mutations per cell division was derived. A retrospective analysis of ALE experiments revealed that passage sizes typically employed in serial passage batch culture ALE experiments led to inefficient production and fixation of beneficial mutations. ALEsim and the results described here will aid in the design of ALE experiments to fit the exact needs of a project while taking into account the resources required and will lower the barriers to entry for this experimental technique. IMPORTANCE ALE is a widely used scientific technique to increase scientific understanding, as well as to create industrially relevant organisms. The manner in which ALE experiments are conducted is highly manual and uniform, with little optimization for efficiency. Such inefficiencies result in suboptimal experiments that can take multiple months to complete. With the availability of automation and computer simulations, we can now perform these experiments in an optimized fashion and can design experiments to generate greater fitness in an accelerated time frame, thereby pushing the limits of what adaptive laboratory evolution can achieve. Copyright © 2017 American Society for Microbiology.
Selectively targeting pain in the trigeminal system
Kim, Hyun Yeong; Kim, Kihwan; Li, Hai Ying; Chung, Gehoon; Park, Chul-Kyu; Kim, Joong Soo; Jung, Sung Jun; Lee, Min Kyung; Ahn, Dong Kuk; Hwang, Se Jin; Kang, Youngnam; Binshtok, Alexander M.; Bean, Bruce P.; Woolf, Clifford J.; Oh, Seog Bae
2015-01-01
We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (INa) and action potentials (APs) in trigeminal ganglion (TG) neurons. However, co-application of QX-314 and capsaicin blocked INa and APs in TRPV1-positive TG and dental nociceptive neurons, but not in TRPV1-negative TG neurons or in small neurons from TRPV1 knock-out mice. Immunohistochemistry revealed that TRPV1 is not expressed by trigeminal motor and trigeminal mesencephalic neurons. Capsaicin had no effect on rat trigeminal motor and proprioceptive mesencephalic neurons and therefore should not allow QX-314 to enter these cells. Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain. PMID:20236764
Kawaguchi, Jun; Matsuura, Nobuyuki; Kasahara, Masataka; Ichinohe, Tatsuya
2015-02-01
The purpose of this study was to investigate the latency and amplitude of trigeminal somatosensory evoked potentials to clarify how nerve function on the contralateral side is affected after cervical sympathetic block (CSB). Subjects comprised 16 volunteers. For CSB, the tip of a needle was contacted with the transverse process of the sixth cervical vertebra on the right side, and lidocaine was injected. Trigeminal somatosensory evoked potentials were recorded bilaterally from C5/C6 scalp positions. Pupil diameters were also measured. Electrical stimulations were applied to the left-side lower lip, and trigeminal somatosensory evoked potentials waveforms derived from both sides of the scalp were recorded. Then, electrical stimulations were applied to the right-side of the lower lip, and recording was again performed. Recordings were performed at 5, 15, and 30 minutes after CSB. On the CSB side, pupil diameter decreased at 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials at contralateral stimulation showed a prolongation of the latency in both P20 and N25 components on bilateral recording sites 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials' amplitude at contralateral stimulation was smaller than at ipsilateral stimulation 5 minutes after CSB. Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.
The association of middle ear effusion with trigeminal nerve mass lesions in dogs.
Wessmann, A; Hennessey, A; Goncalves, R; Benigni, L; Hammond, G; Volk, H A
2013-11-09
The trigeminal nerve is involved in the opening of the pharyngeal orifice of the Eustachian tube by operating the tensor veli palatini muscle. The hypothesis was investigated that middle ear effusion occurs in a more severe disease phenotype of canine trigeminal nerve mass lesions compared with dogs without middle ear effusion. Three observers reviewed canine MRIs with an MRI-diagnosis of trigeminal nerve mass lesion from three institutions. Various parameters describing the musculature innervated by the trigeminal nerve were scored and compared between dogs with and without middle ear effusion. Nineteen dogs met the inclusion criteria. Ipsilateral middle ear effusion was observed in 63 per cent (95% CI 48.4 per cent to 77.6 per cent) of the dogs. The size of the trigeminal nerve mass lesions was positively correlated with the severity of masticatory muscle mass loss (Spearman r=0.5, P=0.03). Dogs with middle ear effusion had a significantly increased generalised masticatory muscle mass loss (P=0.02) or tensor veli palatini muscle loss score (P=0.03) compared with those without. Larger trigeminal nerve mass lesions were associated with a greater degree of masticatory muscle mass loss. Masticatory muscle mass and, importantly, tensor veli palatini muscle mass was more severely affected in dogs with middle ear effusion suggesting an associated Eustachian tube dysfunction.
2010-01-01
Background Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic inflammatory diseases. The goal of this study was to investigate effects of grape seed extract on neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis in response to persistent temporomandibular joint inflammation. Sprague Dawley rats were pretreated with 200 mg/kg/d MegaNatural-BP grape seed extract for 14 days prior to bilateral injections of complete Freund's adjuvant into the temporomandibular joint capsule. Results In response to grape seed extract, basal expression of mitogen-activated protein kinase phosphatase 1 was elevated in neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis, and expression of the glutamate aspartate transporter was increased in spinal glia. Rats on a normal diet injected with adjuvant exhibited greater basal levels of phosphorylated-p38 in trigeminal ganglia neurons and spinal neurons and microglia. Similarly, immunoreactive levels of OX-42 in microglia and glial fibrillary acidic protein in astrocytes were greatly increased in response to adjuvant. However, adjuvant-stimulated levels of phosphorylated-p38, OX-42, and glial fibrillary acidic protein were significantly repressed in extract treated animals. Furthermore, grape seed extract suppressed basal expression of the neuropeptide calcitonin gene-related peptide in spinal neurons. Conclusions Results from our study provide evidence that grape seed extract may be beneficial as a natural therapeutic option for temporomandibular joint disorders by suppressing development of peripheral and central sensitization. PMID:21143976
Puri, Jyoti; Bellinger, Larry L.; Kramer, Phillip R.
2011-01-01
Females report temporomandibular joint (TMJ) pain more than men and studies suggest estrogen modulates this pain response. Our goal in this study was to determine genes that are modulated by physiological levels of 17β-estradiol that could have a role in TMJ pain. To complete this goal, saline or complete Freund’s adjuvant was injected in the TMJ when plasma 17β-estradiol was low or when it was at a high proestrus level. TMJ, trigeminal ganglion and trigeminal subnucleus caudalis/upper cervical cord junction (Vc/C1–2) tissues were isolated from the treated rats and expression of 184 genes was quantitated in each tissue using real time PCR. Significant changes in the amount of specific transcripts were observed in the TMJ tissues, trigeminal ganglia and Vc/C1–2 region when comparing rats with high and low estrogen. GABA A receptor subunit α6 (Gabra6) and the glycine receptor α2 (Glra2) were two genes of interest because of their direct function in neuronal activity and a greater than 29 fold increase in the trigeminal ganglia was observed in proestrus rats with TMJ inflammation. Immunohistochemical studies showed that Gabrα6 and Glrα2 neuronal and not glial expression increased when comparing rats with high and low estrogen. Estrogen receptors α and β are present in neurons of the trigeminal ganglia, whereby 17β-estradiol can alter expression of Gabrα6 and Glrα2. Also, estrogen receptor α (ERα) but not ERβ was observed in satellite glial cells of the trigeminal ganglia. These results demonstrate that genes associated with neurogenic inflammation or neuronal excitability were altered by changes in the concentration of 17β-estradiol. PMID:21321935
NASA Astrophysics Data System (ADS)
Thurrell, Adrian; Pelah, Adar
2005-03-01
We report on recent experiments to investigate the Arthrovisual Locomotor Effect (ALE), a mechanism based on non-visual signals postulated to discount or remove the self-generated visual motion signals during locomotion. It is shown that perceptual matches made by standing subjects to a constant motion optic flow stimulus that is viewed while walking on a treadmill are linearly reduced by walking speed, a measure of the reported ALE. The degree of reduction in perceived speed depends on the similarity of the motor activity to natural locomotion, thus for the four activities tested, ALE strength is ranked as follows: Walking > Cycling > Hand Pedalling > Finger Tapping = 0. Other variations and important controls for the ALE are described.
Update on neuropathic pain treatment for trigeminal neuralgia
Al-Quliti, Khalid W.
2015-01-01
Trigeminal neuralgia is a syndrome of unilateral, paroxysmal, stabbing facial pain, originating from the trigeminal nerve. Careful history of typical symptoms is crucial for diagnosis. Most cases are caused by vascular compression of the trigeminal root adjacent to the pons leading to focal demyelination and ephaptic axonal transmission. Brain imaging is required to exclude secondary causes. Many medical and surgical treatments are available. Most patients respond well to pharmacotherapy; carbamazepine and oxcarbazepine are first line therapy, while lamotrigine and baclofen are considered second line treatments. Other drugs such as topiramate, levetiracetam, gabapentin, pregabalin, and botulinum toxin-A are alternative treatments. Surgical options are available if medications are no longer effective or tolerated. Microvascular decompression, gamma knife radiosurgery, and percutaneous rhizotomies are most promising surgical alternatives. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on available evidence and guidelines. PMID:25864062
The trigeminal trophic syndrome: an unusual cause of nasal ulceration.
Monrad, Seetha U; Terrell, Jeffrey E; Aronoff, David M
2004-06-01
Trigeminal trophic syndrome (TTS) is an unusual complication after peripheral or central damage to the trigeminal nerve, characterized by anesthesia, paresthesias, and ala nasi ulceration. We describe a patient with classic TTS after trigeminal rhizotomy who underwent several extensive evaluations for nasal ulceration and received prolonged immunosuppressive therapy for a presumed autoimmune disorder before the correct diagnosis was made. An understanding of the predisposing factors and clinical presentation of TTS is important to ensure a timely diagnosis of this difficult-to-treat illness. Differentiation of TTS from malignancy, infection, or vasculitis is possible on the basis of clinical history, tissue biopsy, and serologic evaluation.
Trigeminal Trophic Syndrome Associated With the Use of Synthetic Marijuana.
Khan, Fawad A; Manacheril, Rinu; Ulep, Robin; Martin, Julie E; Chimakurthy, Anil
2017-01-01
Trigeminal trophic syndrome (TTS) is an uncommon disorder of the trigeminal nerve tract and trigeminal brainstem nucleus. The syndrome is characterized by a triad of unilateral crescentic ulcers with anesthesia and paresthesias of the involved trigeminal dermatomes. A 24-year-old right-handed black female presented to our emergency department with a 4-week history of rapidly progressive painless desquamation/denudation of skin over her right face and scalp. Four weeks prior, she had been admitted to another institution for seizures and was diagnosed with seizures provoked by synthetic marijuana use. She was afebrile during her initial presentation at our institution. Dermatologic examination revealed denudation of the epidermis and partial dermis over the right frontal, parietal, and temporal scalp with associated alopecia. To our knowledge, the association of disorders of the trigeminal nerve pathway, including TTS, with the use of synthetic marijuana has not been previously reported. The long-term neurologic effects of synthetic marijuana are difficult to predict, and the pathologic underpinnings of TTS are largely unknown. Further studies dedicated to exploring the underlying molecular and cellular mechanisms may translate into effective therapies and approaches to halt and reverse the process and prevent tissue destruction and cosmetic disfigurement.
Flohr, Elena L R; Boesveldt, Sanne; Haehner, Antje; Iannilli, Emilia; Sinding, Charlotte; Hummel, Thomas
2015-03-01
Habituation of responses to chemosensory signals has been explored in many ways. Strong habituation and adaptation processes can be observed at the various levels of processing. For example, with repeated exposure, amplitudes of chemosensory event-related potentials (ERP) decrease over time. However, long-term habituation has not been investigated so far and investigations of differences in habituation between trigeminal and olfactory ERPs are very rare. The present study investigated habituation over a period of approximately 80 min for two olfactory and one trigeminal stimulus, respectively. Habituation was examined analyzing the N1 and P2 amplitudes and latencies of chemosensory ERPs and intensity ratings. It was shown that amplitudes of both components - and intensity ratings - decreased from the first to the last block. Concerning ERP latencies no effects of habituation were seen. Amplitudes of trigeminal ERPs diminished faster than amplitudes of olfactory ERPs, indicating that the habituation of trigeminal ERPs is stronger than habituation of olfactory ERPs. Amplitudes of trigeminal ERPs were generally higher than amplitudes of olfactory ERPs, as it has been shown in various studies before. The results reflect relatively selective central changes in response to chemosensory stimuli over time. Copyright © 2015 Elsevier B.V. All rights reserved.
Lukács, M; Warfvinge, K; Kruse, L S; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L
2016-12-01
Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.
Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review
Kumar, S; Rastogi, S; Kumar, S; Mahendra, P; Bansal, M; Chandra, L
2013-01-01
Abstract Trigeminal neuralgia (TN) is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain within the distribution of one or more branches of the trigeminal nerve. It is the most frequent cranial neuralgia, the incidence being 1 per 1,000,00 persons per year. Pain attacks start abruptly and last several seconds but may persist 1 to 2 minutes. The attacks are initiated by non painful physical stimulation of specific areas (trigger points or zones) that are located ipsilateral to the pain. After each episode, there is usually a refractive period during which stimulation of the trigger zone will not induce the pain. According to the European Federation of Neurological Societies (EFNS) guidelines on neuropathic pain assessment and the American Academy of Neurology (AAN)-EFNS guidelines on TN management the neurophysiological recording of trigeminal reflexes represents the most useful and reliable test for the neurophysiological diagnosis of trigeminal pains. The present article discusses different techniques for investigation of the trigeminal system by which an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain. PMID:24701256
Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review.
Kumar, S; Rastogi, S; Kumar, S; Mahendra, P; Bansal, M; Chandra, L
2013-01-01
Trigeminal neuralgia (TN) is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain within the distribution of one or more branches of the trigeminal nerve. It is the most frequent cranial neuralgia, the incidence being 1 per 1,000,00 persons per year. Pain attacks start abruptly and last several seconds but may persist 1 to 2 minutes. The attacks are initiated by non painful physical stimulation of specific areas (trigger points or zones) that are located ipsilateral to the pain. After each episode, there is usually a refractive period during which stimulation of the trigger zone will not induce the pain. According to the European Federation of Neurological Societies (EFNS) guidelines on neuropathic pain assessment and the American Academy of Neurology (AAN)-EFNS guidelines on TN management the neurophysiological recording of trigeminal reflexes represents the most useful and reliable test for the neurophysiological diagnosis of trigeminal pains. The present article discusses different techniques for investigation of the trigeminal system by which an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.
Optimized adipose tissue engineering strategy based on a neo-mechanical processing method.
He, Yunfan; Lin, Maohui; Wang, Xuecen; Guan, Jingyan; Dong, Ziqing; Feng, Lu; Xing, Malcolm; Feng, Chuanbo; Li, Xiaojian
2018-05-26
Decellularized adipose tissue (DAT) represents a promising scaffold for adipose tissue engineering. However, the unique and prolonged lipid removal process required for adipose tissue can damage extracellular matrix (ECM) constituents. Moreover, inadequate vascularization limits the recellularization of DAT in vivo. We proposed a neo-mechanical protocol for rapidly breaking adipocytes and removing lipid content from adipose tissue. The lipid-depleted adipose tissue was then subjected to a fast and mild decellularization to fabricate high-quality DAT (M-DAT). Adipose liquid extract (ALE) derived from this mechanical process was collected and incorporated into M-DAT to further optimize in vivo recellularization. Ordinary DAT was fabricated and served as a control. This developed strategy was evaluated based on decellularization efficiency, ECM quality, and recellularization efficiency. Angiogenic factor components and angiogenic potential of ALE were evaluated in vivo and in vitro. M-DAT achieved the same decellularization efficiency, but exhibited better retention of ECM components and recellularization, compared to those with ordinary DAT. Protein quantification revealed considerable levels of angiogenic factors (basic fibroblast growth factor, epidermal growth factor, transforming growth factor-β1, and vascular endothelial growth factor) in ALE. ALE promoted tube formation in vitro and induced intense angiogenesis in M-DAT in vivo; furthermore, higher expression of the adipogenic factor PPARγ and greater numbers of adipocytes were evident following ALE treatment, compared to those in the M-DAT group. Mechanical processing of adipose tissue led to the production of high-quality M-DAT and angiogenic factor-enriched ALE. The combination of ALE and M-DAT could be a promising strategy for engineered adipose tissue construction. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.
Yao, Wei; Evan Lay, Yu-An; Kot, Alexander; Liu, Ruiwu; Zhang, Hongliang; Chen, Haiyan; Lam, Kit; Lane, Nancy E.
2017-01-01
Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 µg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 × 105, IV) or ADSC + LLP2A-Ale. In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent. There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. PMID:27334693
Modeling of Complex Coupled Fluid-Structure Interaction Systems in Arbitrary Water Depth
2008-01-01
model in a particle finite element method ( PFEM ) based framework for the ALE-RANS solver and submitted a journal paper recently [1]. In the paper, we...developing a fluid-flexible structure interaction model without free surface using ALE-RANS and k-ε turbulence closure model implemented by PFEM . In...the ALE_RANS and k-ε turbulence closure model based on the particle finite element Method ( PFEM ) and obtained some satisfying results [1-2]. The
NASA Astrophysics Data System (ADS)
Kronsteiner, J.; Horwatitsch, D.; Zeman, K.
2017-10-01
Thermo-mechanical numerical modelling and simulation of extrusion processes faces several serious challenges. Large plastic deformations in combination with a strong coupling of thermal with mechanical effects leads to a high numerical demand for the solution as well as for the handling of mesh distortions. The two numerical methods presented in this paper also reflect two different ways to deal with mesh distortions. Lagrangian Finite Element Methods (FEM) tackle distorted elements by building a new mesh (called re-meshing) whereas Arbitrary Lagrangian Eulerian (ALE) methods use an "advection" step to remap the solution from the distorted to the undistorted mesh. Another difference between conventional Lagrangian and ALE methods is the separate treatment of material and mesh in ALE, allowing the definition of individual velocity fields. In theory, an ALE formulation contains the Eulerian formulation as a subset to the Lagrangian description of the material. The investigations presented in this paper were dealing with the direct extrusion of a tube profile using EN-AW 6082 aluminum alloy and a comparison of experimental with Lagrangian and ALE results. The numerical simulations cover the billet upsetting and last until one third of the billet length is extruded. A good qualitative correlation of experimental and numerical results could be found, however, major differences between Lagrangian and ALE methods concerning thermo-mechanical coupling lead to deviations in the thermal results.
Johnson, Neil J; Hanson, Leah R; Frey, William H
2010-06-07
Intranasal delivery has been shown to noninvasively deliver drugs from the nose to the brain in minutes along the olfactory and trigeminal nerve pathways, bypassing the blood-brain barrier. However, no one has investigated whether nasally applied drugs target orofacial structures, despite high concentrations observed in the trigeminal nerve innervating these tissues. Following intranasal administration of lidocaine to rats, trigeminally innervated structures (teeth, temporomandibular joint (TMJ), and masseter muscle) were found to have up to 20-fold higher tissue concentrations of lidocaine than the brain and blood as measured by ELISA. This concentration difference could allow intranasally administered therapeutics to treat disorders of orofacial structures (i.e., teeth, TMJ, and masseter muscle) without causing unwanted side effects in the brain and the rest of the body. In this study, an intranasally administered infrared dye reached the brain within 10 minutes. Distribution of dye is consistent with dye entering the trigeminal nerve after intranasal administration through three regions with high drug concentrations in the nasal cavity: the middle concha, the maxillary sinus, and the choana. In humans the trigeminal nerve passes through the maxillary sinus to innervate the maxillary teeth. Delivering lidocaine intranasally may provide an effective anesthetic technique for a noninvasive maxillary nerve block. Intranasal delivery could be used to target vaccinations and treat disorders with fewer side effects such as tooth pain, TMJ disorder, trigeminal neuralgia, headache, and brain diseases.
Keep, Marcus F; DeMare, Paul A; Ashby, Lynn S
2005-01-01
The authors tested the hypothesis that two targets are needed to treat postherpetic trigeminal neuralgia (TN): one in the trigeminal nerve for the direct sharp pain and one in the thalamus for the diffuse burning pain. Three patients with refractory postherpetic TN were treated with gamma knife surgery (GKS) through a novel two-target approach. In a single treatment session, both the trigeminal nerve and centromedian nucleus were targeted. First, the trigeminal nerve, ipsilateral to the facial pain, was treated with 60 to 80 Gy. Second, the centromedian nucleus was localized using standard coordinates and by comparing magnetic resonance images with a stereotactic atlas. A single dose of 120 to 140 Gy was delivered to the target point with a single 4-mm isocenter. Patients were followed clinically and with neuroimaging studies. Pain relief was scored as excellent (75-100%), good (50-75%), poor (25-50%); or none (0-25%). Follow up ranged from 6 to 53 months. There were no GKS-related complications. Two patients died of unrelated medical illnesses but had good or excellent pain relief until death. One patient continues to survive with 44 months follow up and no decrease in pain intensity, but with a decreased area of pain. Combined GKS of the centromedian nucleus and trigeminal nerve in a single treatment session is feasible and safe, and the effect was promising. A larger study is required to confirm and expand these results.
The nucleus raphe magnus OFF-cells are involved in diffuse noxious inhibitory controls.
Chebbi, R; Boyer, N; Monconduit, L; Artola, A; Luccarini, P; Dallel, R
2014-06-01
Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting descending inhibitory controls which are pivotal in modulating the activity of spinal and trigeminal nociceptive neurons. DNIC are subserved by a loop involving supraspinal structures such as the lateral parabrachial nucleus and the subnucleus reticularis dorsalis. Surprisingly, though, whether the nucleus raphe magnus (NRM), another supraspinal area which is long known to be important in pain modulation, is involved in DNIC is still a matter of discussion. Here, we reassessed the role of the NRM neurons in DNIC by electrophysiologically recording from wide dynamic range (WDR) neurons in the trigeminal subnucleus oralis and pharmacologically manipulating the NRM OFF- and ON-cells. In control conditions, C-fiber-evoked responses in trigeminal WDR neurons are inhibited by a conditioning noxious heat stimulation applied to the hindpaw. We show that inactivating the NRM by microinjecting the GABAA receptor agonist, muscimol, both facilitates C-fiber-evoked responses of trigeminal WDR neurons and strongly attenuates their inhibition by heat applied to the hindpaw. Interestingly, selective blockade of ON-cells by microinjecting the broad-spectrum excitatory amino acid antagonist, kynurenate, into the NRM neither affects C-fiber-evoked responses nor attenuates DNIC of trigeminal WDR neurons. These results indicate that the NRM tonically inhibits trigeminal nociceptive inputs and is involved in the neuronal network underlying DNIC. Moreover, within NRM, OFF-cells might be more specifically involved in both the tonic and phasic descending inhibitory controls of trigeminal nociception. Copyright © 2014 Elsevier Inc. All rights reserved.
Intracranial stimulation of the trigeminal nerve in man. III. Sensory potentials.
Cruccu, G; Inghilleri, M; Manfredi, M; Meglio, M
1987-01-01
Percutaneous electrical stimulation of the trigeminal root was performed in 18 subjects undergoing surgery for idiopathic trigeminal neuralgia or implantation of electrodes into Meckel's cave for recording of limbic epileptic activity. All subjects had normal trigeminal reflexes and evoked potentials. Sensory action potentials were recorded antidromically from the supraorbital (V1), infraorbital (V2) and mental (V3) nerves. In the awake subject, sensory potentials were usually followed by myogenic artifacts due to direct activation of masticatory muscles or reflex activation of facial muscles. In the anaesthetised and curarised subject, sensory potentials from the three nerves showed 1.4-2.2 ms onset latency, 1.9-2.7 ms peak latency and 17-29 microV amplitude. Sensory conduction velocity was computed at the onset latency (maximum CV) and at the peak latency (peak CV). On average, maximum and peak CV were 52 and 39 m/s for V1, 54 and 42 m/s for V2 and 54 and 44 m/s for V3. There was no apparent difference in CV between subjects with trigeminal neuralgia and those with epilepsy. A significant inverse correlation was found between CV and age, the overall maximum CV declining from 59 m/s (16 years) to 49 m/s (73 years). This range of CV is compatible both with histometric data and previous electrophysiological findings on trigeminal nerve conduction. Intraoperative intracranial stimulation is also proposed as a method of monitoring trigeminal function under general anaesthesia. Images PMID:3681311
NASA Astrophysics Data System (ADS)
Skrutskie, Michael F.; de Kleer, Katherine R.; Stone, Jordan; Conrad, Al; Davies, Ashley; de Pater, Imke; Leisenring, Jarron; Hinz, Philip; Skemer, Andrew; Veillet, Christian; Woodward, Charles E.; Ertel, Steve; Spalding, Eckhart
2017-10-01
The Arizona Lenslet for Exoplanet Spectroscopy (ALES) is an enhancement to the Large Binocular Telescope's mid-infrared imager, LMIRcam, that permits low-resolution (R~20) spectroscopy between 2.8 and 4.2 μm of every diffraction-limited resolution element in a 2.5"x2.5" field-of-view on a 2048x2048 HAWAII-2RG 5.2 μm-cutoff array. The 1" disk of Io, dotted with powerful self-luminous volcanic eruptions, provides an ideal target for ALES, where the single 8.4-meter aperture diffraction-limited scale for Io at opposition ranges from 240 kilometers (80 milliarcseconds) at 2.8 μm to 360 kilometers (120 milliarcseconds) at 4.2 μm. ALES provides the capability to assess the color temperature of each volcanic thermal emission site as well as map broadband absorbers such as SO2 frost. A monitoring campaign in the Spring 2017 semester provided two global snapshots of Io's volcanic activity with ALES as well as characterization of a new brightening episode at Loki Patera over four epochs between January and May 2017.
... Bland foods, such as gelatin, frozen desserts, broth, ginger ale, and saltine crackers, also soothe the stomach. ... your stomach does not get too full. Seltzer, ginger ale, or other sparkling waters may help control ...
Han, Xun; Ran, Ye; Su, Min; Liu, Yinglu; Tang, Wenjing; Dong, Zhao; Yu, Shengyuan
2017-01-01
Background Preclinical experimental studies revealed an acute alteration of pituitary adenylate cyclase-activating polypeptide in response to a single activation of the trigeminovascular system, which suggests a potential role of pituitary adenylate cyclase-activating polypeptide in the pathogenesis of migraine. However, changes in pituitary adenylate cyclase-activating polypeptide after repeated migraine-like attacks in chronic migraine are not clear. Therefore, the present study investigated chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulations in the rat. Methods A rat model of chronic migraine was established by repeated chemical dural stimulations using an inflammatory soup for a different numbers of days. The pituitary adenylate cyclase-activating polypeptide levels were quantified in plasma, the trigeminal ganglia, and the trigeminal nucleus caudalis using radioimmunoassay and Western blotting in trigeminal ganglia and trigeminal nucleus caudalis tissues. Western blot analysis and real-time polymerase chain reaction were used to measure the protein and mRNA expression of pituitary adenylate cyclase-activating polypeptide-related receptors (PAC1, VPAC1, and VPAC2) in the trigeminal ganglia and trigeminal nucleus caudalis to identify changes associated with repetitive applications of chemical dural stimulations. Results All rats exhibited significantly decreased periorbital nociceptive thresholds to repeated inflammatory soup stimulations. Radioimmunoassay and Western blot analysis demonstrated significantly decreased pituitary adenylate cyclase-activating polypeptide levels in plasma and trigeminal ganglia after repetitive chronic inflammatory soup stimulation. Protein and mRNA analyses of pituitary adenylate cyclase-activating polypeptide-related receptors demonstrated significantly increased PAC1 receptor protein and mRNA expression in the trigeminal ganglia, but not in the trigeminal nucleus caudalis, and no significant differences were found in the expression of the VPAC1 and VPAC2 receptors. Conclusions This study demonstrated the chronic alteration of pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in the rat, which suggests the crucial involvement of pituitary adenylate cyclase-activating polypeptide in the development of migraine. The selective increase in pituitary adenylate cyclase-activating polypeptide-related receptors suggests that the PAC1 receptor pathway is a novel target for the treatment of migraine.
Trigeminal neuralgia treatment dosimetry of the Cyberknife
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ho, Anthony; Lo, Anthony T., E-mail: tonyho22003@yahoo.com; Dieterich, Sonja
2012-04-01
There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patient's right, whereas the second is on the patient's left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculationmore » algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.« less
NASA Astrophysics Data System (ADS)
Maher, Nicola; England, Matthew H.; Gupta, Alex Sen; Spence, Paul
2018-05-01
Patients with the feeling of a congested nose not always suffer from an anatomical obstruction but might just have a low trigeminal sensibility, which prevents them from perceiving the nasal airstream. We examined whether intermittent trigeminal stimulation increases sensitivity of the nasal trigeminal nerve and whether this effect is accompanied by subjective improvement of nasal breathing.
Feistel, Stephan; Albrecht, Stephanie; Messlinger, Karl
2013-11-20
Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches.
St. John, James A.; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W.; Batzloff, Michael R.
2016-01-01
Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. PMID:27382023
Neurovascular Study of the Trigeminal Nerve at 3 T MRI
Gonzalez, Nadia; Muñoz, Alexandra; Bravo, Fernando; Sarroca, Daniel; Morales, Carlos
2015-01-01
This study aimed to show a novel visualization method to investigate neurovascular compression of the trigeminal nerve (TN) using a volume-rendering fusion imaging technique of 3D fast imaging employing steady-state acquisition (3D FIESTA) and coregistered 3D time of flight MR angiography (3D TOF MRA) sequences, which we called “neurovascular study of the trigeminal nerve”. We prospectively studied 30 patients with unilateral trigeminal neuralgia (TN) and 50 subjects without symptoms of TN (control group), on a 3 Tesla scanner. All patients were assessed using 3D FIESTA and 3D TOF MRA sequences centered on the pons, as well as a standard brain protocol including axial T1, T2, FLAIR and GRE sequences to exclude other pathologies that could cause TN. Post-contrast T1-weighted sequences were also performed. All cases showing arterial imprinting on the trigeminal nerve (n = 11) were identified on the ipsilateral side of the pain. No significant relationship was found between the presence of an artery in contact with the trigeminal nerve and TN. Eight cases were found showing arterial contact on the ipsilateral side of the pain and five cases of arterial contact on the contralateral side. The fusion imaging technique of 3D FIESTA and 3D TOF MRA sequences, combining the high anatomical detail provided by the 3D FIESTA sequence with the 3D TOF MRA sequence and its capacity to depict arterial structures, results in a tool that enables quick and efficient visualization and assessment of the relationship between the trigeminal nerve and the neighboring vascular structures. PMID:25924169
Cyto- and chemoarchitecture of the sensory trigeminal nuclei of the echidna, platypus and rat.
Ashwell, Ken W S; Hardman, Craig D; Paxinos, George
2006-02-01
We have examined the cyto- and chemoarchitecture of the trigeminal nuclei of two monotremes using Nissl staining, enzyme reactivity for cytochrome oxidase, immunoreactivity for calcium binding proteins and non-phosphorylated neurofilament (SMI-32 antibody) and lectin histochemistry (Griffonia simplicifolia isolectin B4). The principal trigeminal nucleus and the oralis and interpolaris spinal trigeminal nuclei were substantially larger in the platypus than in either the echidna or rat, but the caudalis subnucleus was similar in size in both monotremes and the rat. The numerical density of Nissl stained neurons was higher in the principal, oralis and interpolaris nuclei of the platypus relative to the echidna, but similar to that in the rat. Neuropil immunoreactivity for parvalbumin was particularly intense in the principal trigeminal, oralis and interpolaris subnuclei of the platypus, but the numerical density of parvalbumin immunoreactive neurons was not particularly high in these nuclei of the platypus. Neuropil immunoreactivity for calbindin and calretinin was relatively weak in both monotremes, although calretinin immunoreactive somata made up a large proportion of neurons in the principal, oralis and interpolaris subnuclei of the echidna. Distribution of calretinin immunoreactivity and Griffonia simplicifolia B4 isolectin reactivity suggested that the caudalis subnucleus of the echidna does not have a clearly defined gelatinosus region. Our findings indicate that the trigeminal nuclei of the echidna do not appear to be highly specialized, but that the principal, oralis and interpolaris subnuclei of the platypus trigeminal complex are highly differentiated, presumably for processing of tactile and electrosensory information from the bill.
Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.
Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke
2015-01-01
Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.
Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism
Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke
2015-01-01
Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus. PMID:26244675
Shelukhina, Irina; Mikhailov, Nikita; Abushik, Polina; Nurullin, Leniz; Nikolsky, Evgeny E; Giniatullin, Rashid
2017-01-01
Parasympathetic innervation of meninges and ability of carbachol, acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests contribution of cholinergic mechanisms to primary headaches. However, neurochemical mechanisms of cholinergic regulation of peripheral nociception in meninges, origin place for headache, are almost unknown. Using electrophysiology, calcium imaging, immunohistochemistry, and staining of meningeal mast cells, we studied effects of cholinergic agents on peripheral nociception in rat hemiskulls and isolated trigeminal neurons. Both ACh and carbachol significantly increased nociceptive firing in peripheral terminals of meningeal trigeminal nerves recorded by local suction electrode. Strong nociceptive firing was also induced by nicotine, implying essential role of nicotinic AChRs in control of excitability of trigeminal nerve endings. Nociceptive firing induced by carbachol was reduced by muscarinic antagonist atropine, whereas the action of nicotine was prevented by the nicotinic blocker d-tubocurarine but was insensitive to the TRPA1 antagonist HC-300033. Carbachol but not nicotine induced massive degranulation of meningeal mast cells known to release multiple pro-nociceptive mediators. Enzymes terminating ACh action, acetylcholinesterase (AChE) and butyrylcholinesterase, were revealed in perivascular meningeal nerves. The inhibitor of AChE neostigmine did not change the firing per se but induced nociceptive activity, sensitive to d-tubocurarine, after pretreatment of meninges with the migraine mediator CGRP. This observation suggested the pro-nociceptive action of endogenous ACh in meninges. Both nicotine and carbachol induced intracellular Ca 2+ transients in trigeminal neurons partially overlapping with expression of capsaicin-sensitive TRPV1 receptors. Trigeminal nerve terminals in meninges, as well as dural mast cells and trigeminal ganglion neurons express a repertoire of pro-nociceptive nicotinic and muscarinic AChRs, which could be activated by the ACh released from parasympathetic nerves. These receptors represent a potential target for novel therapeutic interventions in trigeminal pain and probably in migraine.
Active Learning in Engineering Education: a (re)introduction
NASA Astrophysics Data System (ADS)
Lima, Rui M.; Andersson, Pernille Hammar; Saalman, Elisabeth
2017-01-01
The informal network 'Active Learning in Engineering Education' (ALE) has been promoting Active Learning since 2001. ALE creates opportunity for practitioners and researchers of engineering education to collaboratively learn how to foster learning of engineering students. The activities in ALE are centred on the vision that learners construct their knowledge based on meaningful activities and knowledge. In 2014, the steering committee of the ALE network reinforced the need to discuss the meaning of Active Learning and that was the base for this proposal for a special issue. More than 40 submissions were reviewed by the European Journal of Engineering Education community and this theme issue ended up with eight contributions, which are different both in their research and Active Learning approaches. These different Active Learning approaches are aligned with the different approaches that can be increasingly found in indexed journals.
Adaptive reconnection-based arbitrary Lagrangian Eulerian method
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bo, Wurigen; Shashkov, Mikhail
We present a new adaptive Arbitrary Lagrangian Eulerian (ALE) method. This method is based on the reconnection-based ALE (ReALE) methodology of Refs. [35], [34] and [6]. The main elements in a standard ReALE method are: an explicit Lagrangian phase on an arbitrary polygonal (in 2D) mesh in which the solution and positions of grid nodes are updated; a rezoning phase in which a new grid is defined by changing the connectivity (using Voronoi tessellation) but not the number of cells; and a remapping phase in which the Lagrangian solution is transferred onto the new grid. Furthermore, in the standard ReALEmore » method, the rezoned mesh is smoothed by using one or several steps toward centroidal Voronoi tessellation, but it is not adapted to the solution in any way.« less
Adaptive reconnection-based arbitrary Lagrangian Eulerian method
Bo, Wurigen; Shashkov, Mikhail
2015-07-21
We present a new adaptive Arbitrary Lagrangian Eulerian (ALE) method. This method is based on the reconnection-based ALE (ReALE) methodology of Refs. [35], [34] and [6]. The main elements in a standard ReALE method are: an explicit Lagrangian phase on an arbitrary polygonal (in 2D) mesh in which the solution and positions of grid nodes are updated; a rezoning phase in which a new grid is defined by changing the connectivity (using Voronoi tessellation) but not the number of cells; and a remapping phase in which the Lagrangian solution is transferred onto the new grid. Furthermore, in the standard ReALEmore » method, the rezoned mesh is smoothed by using one or several steps toward centroidal Voronoi tessellation, but it is not adapted to the solution in any way.« less
Apocynum venetum Attenuates Acetaminophen-Induced Liver Injury in Mice.
Xie, Wenyan; Chen, Chen; Jiang, Zhihui; Wang, Jian; Melzig, Matthias F; Zhang, Xiaoying
2015-01-01
Apocynum venetum L. (A. venetum) has long been used in oriental folk medicine for the treatment of some liver diseases; however, the underlying mechanisms remain to be fully elucidated. Acetaminophen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. In this study, we investigated the potential protective effect of A. venetum leaf extract (ALE) against APAP-induced hepatotoxicity. Mice were intragastrically administered with ALE once daily for 3 consecutive days prior to receiving a single intraperitoneal injection of APAP. The APAP group showed severe liver injury characterized by the noticeable fluctuations in the following parameters: serum aminotransferases; hepatic malondialdehyde (MDA), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH). These liver damages induced by APAP were significantly attenuated by ALE pretreatments. A collective analysis of histopathological examination, DNA laddering and western blot for caspase-3 and cytochrome c indicated that the ALE is also capable of preventing APAP-induced hepatocyte death. Hyperoside, isoquercitrin and their derivatives have been identified as the major components of ALE using HPLC-MS/MS. Taken together, the A. venetum possesses hepatoprotective effects partially due to its anti-oxidant action.
Yang, Woong-Suk; Lee, Sung Ryul; Jeong, Yong Joon; Park, Dae Won; Cho, Young Mi; Joo, Hae Mi; Kim, Inhye; Seu, Young-Bae; Sohn, Eun-Hwa; Kang, Se Chan
2016-05-11
The antiallergic potential of Arctium lappa L. was investigated in Sprague-Dawley rats, ICR mice, and RBL-2H3 cells. Ethanol extract (90%) of A. lappa (ALE, 100 μg/mL) inhibited the degranulation rate by 52.9%, determined by the level of β-hexosaminidase. ALE suppressed passive cutaneous anaphylaxis (PCA) in rats and attenuated anaphylaxis and histamine release in mice. To identify the active compound of ALE, we subsequently fractionated and determined the level of β-hexosaminidase in all subfractions. Oleamide was identified as an active compound of ALE, which attenuated the secretion of histamine and the production of tumor necrosis factor (TNF)-α and interleukin-4 (IL-4) in cells treated with compound 48/80 or A23187/phorbol myristate acetate (PMA). Oleamide suppressed FcεRI-tyrosine kinase Lyn-mediated pathway, c-Jun N-terminal kinases (JNK/SAPK), and p38 mitogen-activated protein kinases (p38-MAPKs). These results showed that ALE and oleamide attenuated allergic reactions and should serve as a platform to search for compounds with antiallergic activity.
2005-06-01
derived cells, we isolated first branchial arch mesenchymal populations, as well as trigeminal ganglion non-neuronal cells, from mouse embryos and measured...demonstrate that loss of neurofibromin affects the invasiveness of neural crest-derived (trigeminal ganglion) and cranial mesenchymal ( branchial arch) cell...trigeminal and branchial arch cells between El0 and El 2 indicates that the roles of neurofibromin in controlling motility may become increasingly
Evaluation of Coastal Sea Level from Jason-2 Altimetry Offshore Hong Kong
NASA Astrophysics Data System (ADS)
Birol, F.; Xu, X. Y., , Dr; Cazenave, A. A.
2017-12-01
In the recent years, several coastal altimetry products of Jason-2 mission have been distributed by different agencies, the most advance ones of which are XTRACK, PISTACH and ALES. Each product represents extraordinary endeavors on some aspects of retracking or advanced geophysical corrections, and each has its advantage. The motivation of this presentation is to evaluate these products in order to refine the sea level measurements at the coast. Three retrackers: MLE4, MLE3 and ALES are focused on. Within 20km coastward, neither GDR nor ALES readily provides sea level anomaly (SLA) measurements, so we recomputed the 20Hz GDR and ALES SLA from the raw data, adopting auxiliary information (such as waveform classification and wet tropospheric delay) from PISTACH. The region of interest is track #153 of the Jason-2 satellite (offshore Hong Kong, China), and the altimetry products are processed over seven years (2008-2015, cycles 1-252). The coastline offshore Hong Kong is rather complicated and we feel that it can be a good indicator of the performance of coastal altimetry under undesirable coast conditions. We computed the bias and noise level of ALES, MLE3 and MLE4 SLA over open ocean and in the coastal zone (within 10km or 5km coast-ward). The results showed that, after outlier-editing, ALES performs better than MLE4 and MLE3 both in terms of noise level and uncertainty in sea level trend estimation. We validated the coastal altimetry-based SLA by comparing with data from the Hong Kong tide gauge (located 10km across-track). An interesting , but still preliminary, result is that the computed sea level trend within 5 km from the coast is significantly larger than the trend estimated at larger distances from the coast. Keywords: Jason-2, Hong Kong coast, ALES, MLE3, MLE4
Stuck, B A; Frey, S; Freiburg, C; Hörmann, K; Zahnert, T; Hummel, T
2006-06-01
For chemosensory event-related potentials (ERP) significant effects of age and sex have been demonstrated. The aim of the present study was to assess the effects of stimulus concentration, side of stimulation, and sex on the topographical distribution of chemosensory ERP in a large group of subjects stratified for different age groups. In addition, psychophysical measures of both olfactory and trigeminal function should be assessed in greater detail compared to previous work. A total of 95 healthy subjects participated in the study. Olfactory functions were tested using the 'Sniffin' Sticks' comprising tests of odor identification, odor discrimination, and odor threshold. Trigeminal sensitivity was assessed on a psychophysical level using a lateralization paradigm. ERP to the olfactory stimulant H2S and the trigeminal irritant CO2 were recorded; stimuli were presented in different concentrations to the left and right nostril. Olfactory thresholds exhibited an age-related increase while the outcome of psychophysical trigeminal tests was not significantly affected by age. In contrast, there was no significant main effect of the factor 'sex' for olfactory tests, while women scored higher than men in the trigeminal task. ERP to olfactory and trigeminal stimuli exhibited a relationship to stimulus concentration, age, and sex with youngest women showing largest amplitudes and shortest latencies. There was no significant main effect of left- or right-sided stimulation on ERP. Measures of olfactory function were found to correlate with parameters of olfactory ERP even when controlling for the subject's age. In addition, correlations between scores in the lateralization task and parameters of the trigeminal ERP were found. Based on electrophysiological data obtained in a large sample size the present results established an age-related loss of olfactory and trigeminal function, which appears to be almost linear. Further, the present results emphasize that responses to chemosensory stimuli are related to sex, while the side of stimulation does not play a major role in the presently used paradigm. Finally, these data establish the lateralization paradigm as a psychophysical tool to investigate intranasal trigeminal function. The present results obtained in a representative group of healthy subjects establishes a comprehensive set of data, which will serve as reference for future work in this area of research.
St John, James A; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W; Ulett, Glen C; Batzloff, Michael R; Beacham, Ifor R; Ekberg, Jenny A K
2016-09-01
Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Schwend, Tyler; Deaton, Ryan J.; Zhang, Yuntao; Caterson, Bruce; Conrad, Gary W.
2012-01-01
Purpose. Sensory trigeminal nerve growth cones innervate the cornea in a highly coordinated fashion. The purpose of this study was to determine if extracellular matrix glycosaminoglycans (ECM–GAGs), including keratan sulfate (KS), dermatan sulfate (DS), and chondroitin sulfate A (CSA) and C (CSC), polymerized in developing eyefronts, may provide guidance cues to nerves during cornea innervation. Methods. Immunostaining using antineuron-specific-β-tubulin and monoclonal antibodies for KS, DS, and CSA/C was performed on eyefronts from embryonic day (E) 9 to E14 and staining visualized by confocal microscopy. Effects of purified GAGs on trigeminal nerve growth cone behavior were tested using in vitro neuronal explant cultures. Results. At E9 to E10, nerves exiting the pericorneal nerve ring grew as tight fascicles, advancing straight toward the corneal stroma. In contrast, upon entering the stroma, nerves bifurcated repeatedly as they extended anteriorly toward the epithelium. KS was localized in the path of trigeminal nerves, whereas DS and CSA/C–rich areas were avoided by growth cones. When E10 trigeminal neurons were cultured on different substrates comprised of purified GAG molecules, their neurite growth cone behavior varied depending on GAG type, concentration, and mode of presentation (immobilized versus soluble). High concentrations of immobilized KS, DS, and CSA/C inhibited neurite growth to varying degrees. Neurites traversing lower, permissive concentrations of immobilized DS and CSA/C displayed increased fasciculation and decreased branching, whereas KS caused decreased fasciculation and increased branching. Enzymatic digestion of sulfated GAGs canceled their effects on trigeminal neurons. Conclusions. Data herein suggest that GAGs may direct the movement of trigeminal nerve growth cones innervating the cornea. PMID:23132805
Yegutkin, Gennady G; Guerrero-Toro, Cindy; Kilinc, Erkan; Koroleva, Kseniya; Ishchenko, Yevheniia; Abushik, Polina; Giniatullina, Raisa; Fayuk, Dmitriy; Giniatullin, Rashid
2016-09-01
Extracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pro-nociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher. CGRP increased ATP and ADP levels in meninges and trigeminal cultures and reduced adenosine concentration in trigeminal cells. Degradation rates for exogenous nucleotides remained similar in control and CGRP-treated meninges, indicating that CGRP triggers nucleotide release without affecting nucleotide-inactivating pathways. Lead nitrate-based enzyme histochemistry of whole mount meninges revealed the presence of high ATPase, ADPase, and AMPase activities, primarily localized in the medial meningeal artery. ATP and ADP induced large intracellular Ca(2+) transients both in neurons and in glial cells whereas AMP and adenosine were ineffective. In trigeminal glia, ATP partially operated via P2X7 receptors. ATP, but not other nucleotides, activated nociceptive spikes in meningeal trigeminal nerve fibers providing a rationale for high degradation rate of pro-nociceptive ATP. Pro-nociceptive effect of ATP in meningeal nerves was reproduced by α,β-meATP operating via P2X3 receptors. Collectively, extracellular ATP, which level is controlled by CGRP, can persistently activate trigeminal nerves in meninges which considered as the origin site of migraine headache. These data are consistent with the purinergic hypothesis of migraine pain and suggest new targets against trigeminal pain.
Panneton, W. Michael; Gan, Qi
2014-01-01
Few trigeminal sensory fibers project centrally beyond the trigeminal sensory complex, with only projections of fibers carried in its sensory anterior ethmoidal (AEN) and intraoral nerves described. Fibers of the AEN project into the brainstem reticular formation where immunoreactivity against substance P and CGRP are found. We investigated whether the source of these peptides could be from trigeminal ganglion neurons by performing unilateral rhizotomies of the trigeminal root and looking for absence of label. After an 8–14 days survival, substance P immunoreactivity in the trigeminal sensory complex was diminished, but we could not conclude that the sole source of this peptide in the lateral parabrachial area and lateral reticular formation arises from primary afferent fibers. Immunoreactivity to CGRP after rhizotomy however was greatly diminished in the trigeminal sensory complex, confirming the observations of others. Moreover, CGRP immunoreactivity was nearly eliminated in fibers in the lateral parabrachial area, the caudal ventrolateral medulla, both the peri-ambiguus and ventral parts of the rostral ventrolateral medulla, in the external formation of the nucleus ambiguus, and diminished in the caudal pressor area. The nearly complete elimination of CGRP in the lateral reticular formation after rhizotomy suggests this peptide is carried in primary afferent fibers. Moreover, the arborization of CGRP immunoreactive fibers in these areas mimics that of direct projections from the AEN. Since electrical stimulation of the AEN induces cardiorespiratory adjustments including an apnea, peripheral vasoconstriction, and bradycardia similar to those seen in the mammalian diving response, we suggest these perturbations of autonomic behavior are enhanced by direct somatic primary afferent projections to these reticular neurons. We believe this to be first description of potential direct somatoautonomic projections to brainstem neurons regulating autonomic activity. PMID:24926231
2011-01-01
Background Calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD. PMID:22145886
Panneton, W Michael; Gan, Qi
2014-01-01
Few trigeminal sensory fibers project centrally beyond the trigeminal sensory complex, with only projections of fibers carried in its sensory anterior ethmoidal (AEN) and intraoral nerves described. Fibers of the AEN project into the brainstem reticular formation where immunoreactivity against substance P and CGRP are found. We investigated whether the source of these peptides could be from trigeminal ganglion neurons by performing unilateral rhizotomies of the trigeminal root and looking for absence of label. After an 8-14 days survival, substance P immunoreactivity in the trigeminal sensory complex was diminished, but we could not conclude that the sole source of this peptide in the lateral parabrachial area and lateral reticular formation arises from primary afferent fibers. Immunoreactivity to CGRP after rhizotomy however was greatly diminished in the trigeminal sensory complex, confirming the observations of others. Moreover, CGRP immunoreactivity was nearly eliminated in fibers in the lateral parabrachial area, the caudal ventrolateral medulla, both the peri-ambiguus and ventral parts of the rostral ventrolateral medulla, in the external formation of the nucleus ambiguus, and diminished in the caudal pressor area. The nearly complete elimination of CGRP in the lateral reticular formation after rhizotomy suggests this peptide is carried in primary afferent fibers. Moreover, the arborization of CGRP immunoreactive fibers in these areas mimics that of direct projections from the AEN. Since electrical stimulation of the AEN induces cardiorespiratory adjustments including an apnea, peripheral vasoconstriction, and bradycardia similar to those seen in the mammalian diving response, we suggest these perturbations of autonomic behavior are enhanced by direct somatic primary afferent projections to these reticular neurons. We believe this to be first description of potential direct somatoautonomic projections to brainstem neurons regulating autonomic activity.
Trigeminal Neuralgia Following Lightning Injury.
López Chiriboga, Alfonso S; Cheshire, William P
2017-01-01
Lightning and other electrical incidents are responsible for more than 300 injuries and 100 deaths per year in the United States alone. Lightning strikes can cause a wide spectrum of neurologic manifestations affecting any part of the neuraxis through direct strikes, side flashes, touch voltage, connecting leaders, or acoustic shock waves. This article describes the first case of trigeminal neuralgia induced by lightning injury to the trigeminal nerve, thereby adding a new syndrome to the list of possible lightning-mediated neurologic injuries.
Shigetani, Yasuyo; Howard, Sara; Guidato, Sonia; Furushima, Kenryo; Abe, Takaya; Itasaki, Nobue
2008-07-15
While most cranial ganglia contain neurons of either neural crest or placodal origin, neurons of the trigeminal ganglion derive from both populations. The Wnt signaling pathway is known to be required for the development of neural crest cells and for trigeminal ganglion formation, however, migrating neural crest cells do not express any known Wnt ligands. Here we demonstrate that Wise, a Wnt modulator expressed in the surface ectoderm overlying the trigeminal ganglion, play a role in promoting the assembly of placodal and neural crest cells. When overexpressed in chick, Wise causes delamination of ectodermal cells and attracts migrating neural crest cells. Overexpression of Wise is thus sufficient to ectopically induce ganglion-like structures consisting of both origins. The function of Wise is likely synergized with Wnt6, expressed in an overlapping manner with Wise in the surface ectoderm. Electroporation of morpholino antisense oligonucleotides against Wise and Wnt6 causes decrease in the contact of neural crest cells with the delaminated placode-derived cells. In addition, targeted deletion of Wise in mouse causes phenotypes that can be explained by a decrease in the contribution of neural crest cells to the ophthalmic lobe of the trigeminal ganglion. These data suggest that Wise is able to function cell non-autonomously on neural crest cells and promote trigeminal ganglion formation.
2013-01-01
Background Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. Methods In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). Results After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. Conclusions CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches. PMID:24256609
Atkinson, M E; Shehab, S A
1986-12-01
In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.
Pain. Part 2a: Trigeminal Anatomy Related to Pain.
Renton, Tara; Egbuniwe, Obi
2015-04-01
In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.
Eickhoff, Simon B; Nichols, Thomas E; Laird, Angela R; Hoffstaedter, Felix; Amunts, Katrin; Fox, Peter T; Bzdok, Danilo; Eickhoff, Claudia R
2016-08-15
Given the increasing number of neuroimaging publications, the automated knowledge extraction on brain-behavior associations by quantitative meta-analyses has become a highly important and rapidly growing field of research. Among several methods to perform coordinate-based neuroimaging meta-analyses, Activation Likelihood Estimation (ALE) has been widely adopted. In this paper, we addressed two pressing questions related to ALE meta-analysis: i) Which thresholding method is most appropriate to perform statistical inference? ii) Which sample size, i.e., number of experiments, is needed to perform robust meta-analyses? We provided quantitative answers to these questions by simulating more than 120,000 meta-analysis datasets using empirical parameters (i.e., number of subjects, number of reported foci, distribution of activation foci) derived from the BrainMap database. This allowed to characterize the behavior of ALE analyses, to derive first power estimates for neuroimaging meta-analyses, and to thus formulate recommendations for future ALE studies. We could show as a first consequence that cluster-level family-wise error (FWE) correction represents the most appropriate method for statistical inference, while voxel-level FWE correction is valid but more conservative. In contrast, uncorrected inference and false-discovery rate correction should be avoided. As a second consequence, researchers should aim to include at least 20 experiments into an ALE meta-analysis to achieve sufficient power for moderate effects. We would like to note, though, that these calculations and recommendations are specific to ALE and may not be extrapolated to other approaches for (neuroimaging) meta-analysis. Copyright © 2016 Elsevier Inc. All rights reserved.
Eickhoff, Simon B.; Nichols, Thomas E.; Laird, Angela R.; Hoffstaedter, Felix; Amunts, Katrin; Fox, Peter T.
2016-01-01
Given the increasing number of neuroimaging publications, the automated knowledge extraction on brain-behavior associations by quantitative meta-analyses has become a highly important and rapidly growing field of research. Among several methods to perform coordinate-based neuroimaging meta-analyses, Activation Likelihood Estimation (ALE) has been widely adopted. In this paper, we addressed two pressing questions related to ALE meta-analysis: i) Which thresholding method is most appropriate to perform statistical inference? ii) Which sample size, i.e., number of experiments, is needed to perform robust meta-analyses? We provided quantitative answers to these questions by simulating more than 120,000 meta-analysis datasets using empirical parameters (i.e., number of subjects, number of reported foci, distribution of activation foci) derived from the BrainMap database. This allowed to characterize the behavior of ALE analyses, to derive first power estimates for neuroimaging meta-analyses, and to thus formulate recommendations for future ALE studies. We could show as a first consequence that cluster-level family-wise error (FWE) correction represents the most appropriate method for statistical inference, while voxel-level FWE correction is valid but more conservative. In contrast, uncorrected inference and false-discovery rate correction should be avoided. As a second consequence, researchers should aim to include at least 20 experiments into an ALE meta-analysis to achieve sufficient power for moderate effects. We would like to note, though, that these calculations and recommendations are specific to ALE and may not be extrapolated to other approaches for (neuroimaging) meta-analysis. PMID:27179606
... Elsevier Saunders; 2015:chap 117. Zakrzewska JM, Chen HI, Lee JYK. Trigeminal and glossopharyngeal neuralgia. In: McMohan ... A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the ...
Fujiwara, M; Hayashi, H; Muramatsu, I; Ueda, N
1984-01-01
The rabbit left ophthalmic nerve (first branch of the left trigeminal nerve) was cut at the intracranial, peripheral side of the trigeminal ganglion and the effects of denervation were examined using iris sphincter muscle preparations isolated from the left and right eye, as denervated and control innervated preparations, respectively. Electrical transmural stimulation produced a substance P-operated contraction, in addition to a cholinergic one, in the preparation isolated from the right control eye. The former response was abolished in the preparation isolated from the left denervated eye, thereby indicating that the trigeminal, substance P nerve ipsilaterally innervates the iris sphincter muscle. Exogenously applied carbachol and substance P produced concentration-dependent contractions in preparations isolated from either eye. Supersensitivity characterized by a decrease in median effective concentration (EC50) values and an increase in maximal response was observed in the responses to both agents of the left denervated preparation. Such supersensitivity developed slowly after trigeminal denervation and 3 weeks was required for full development. Exogenously applied KCl produced substance P-operated and direct muscle contractions in the right control preparations. In the left denervated preparations, the substance P-operated contraction was either markedly attenuated or abolished, while the direct muscle-related contraction was enhanced after trigeminal denervation. The length of the left denervated preparation was longer than that of the right control preparation, and the resting tensions required to produce maximal carbachol contraction shifted to lower values. These physical changes of the iris sphincter muscle developed within 5 days after trigeminal denervation. In the non-denervated preparation treated with capsaicin in vitro, electrical transmural stimulation and KCl failed to produce the substance P-related contraction. However, supersensitivity to neither exogenously applied substance P, carbachol and KCl nor physical changes were observed in the capsaicin-treated preparation. These results suggest that trigeminal, substance P-related nerves tonically and ipsilaterally innervate the rabbit iris sphincter muscle and that the denervation results in non-specific supersensitivity. These findings are essentially the same as those observed in various types of smooth muscles after autonomic denervation. PMID:6205140
Parker, Neva; James, Steve; Dicks, Jo; Bond, Chris; Nueno-Palop, Carmen; White, Chris; Roberts, Ian N
2015-01-01
Five British ale yeast strains were subjected to flavour profiling under brewery fermentation conditions in which all other brewing parameters were kept constant. Significant variation was observed in the timing and quantity of flavour-related chemicals produced. Genetic tests showed no evidence of hybrid origins in any of the strains, including one strain previously reported as a possible hybrid of Saccharomyces cerevisiae and S. bayanus. Variation maintained in historical S. cerevisiae ale yeast collections is highlighted as a potential source of novelty in innovative strain improvement for bioflavour production. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25361168
Posteriori error determination and grid adaptation for AMR and ALE computational fluid dynamics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lapenta, G. M.
2002-01-01
We discuss grid adaptation for application to AMR and ALE codes. Two new contributions are presented. First, a new method to locate the regions where the truncation error is being created due to an insufficient accuracy: the operator recovery error origin (OREO) detector. The OREO detector is automatic, reliable, easy to implement and extremely inexpensive. Second, a new grid motion technique is presented for application to ALE codes. The method is based on the Brackbill-Saltzman approach but it is directly linked to the OREO detector and moves the grid automatically to minimize the error.
Negre-Salvayre, A; Coatrieux, C; Ingueneau, C; Salvayre, R
2008-01-01
Reactive carbonyl compounds (RCCs) formed during lipid peroxidation and sugar glycoxidation, namely Advanced lipid peroxidation end products (ALEs) and Advanced Glycation end products (AGEs), accumulate with ageing and oxidative stress-related diseases, such as atherosclerosis, diabetes or neurodegenerative diseases. RCCs induce the 'carbonyl stress' characterized by the formation of adducts and cross-links on proteins, which progressively leads to impaired protein function and damages in all tissues, and pathological consequences including cell dysfunction, inflammatory response and apoptosis. The prevention of carbonyl stress involves the use of free radical scavengers and antioxidants that prevent the generation of lipid peroxidation products, but are inefficient on pre-formed RCCs. Conversely, carbonyl scavengers prevent carbonyl stress by inhibiting the formation of protein cross-links. While a large variety of AGE inhibitors has been developed, only few carbonyl scavengers have been tested on ALE-mediated effects. This review summarizes the signalling properties of ALEs and ALE-precursors, their role in the pathogenesis of oxidative stress-associated diseases, and the different agents efficient in neutralizing ALEs effects in vitro and in vivo. The generation of drugs sharing both antioxidant and carbonyl scavenger properties represents a new therapeutic challenge in the treatment of carbonyl stress-associated diseases.
El-Boshy, Mohamed; Ashshi, Ahmad; Gaith, Mazen; Qusty, Naeem; Bokhary, Thalat; AlTaweel, Nagwa; Abdelhady, Mohamed
2017-05-01
Our objective was to explore the protective effect of artichoke leaf extract (ALE) against cadmium (Cd) toxicity-induced oxidative organ damage in rats. Male albino Wistar rats were divided into four equal groups of eight animals each. The first group was assigned as a control. Groups 2-4 were orally administered with ALE (300 mg/kg bw), Cd (CdCl 2 , 100 mg/L drinking water), and ALE plus Cd, respectively, daily for 4 weeks. After treatment with Cd, the liver and kidney malondialdehyde (MDA) increased significantly compared with the control rats. The sera interleukin (IL)-1β, tumor necrosis factor (TNF-α), and IL-10, liver transaminase, urea, creatinine, and peripheral neutrophil count were significantly increased in Cd-exposed rats compared to the control group. The reduced glutathione (GSH), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) decreased in the liver and kidney in Cd-exposed group. In combination treatment, Cd and ALE significantly improved immune response, an antioxidant system, and hepatorenal function with a significant decline in MDA. In conclusion, ALE ameliorates the immunosuppressive and hepatorenal oxidative injury stimulated by Cd in rats. These results suggest that artichoke has shown promising effects against adverse effects of Cd toxicity.
Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation.
Kim, Young-Kyu; Koppula, Sushruta; Shim, Do-Wan; In, Eun-Jung; Kwak, Su-Bin; Kim, Myong-Ki; Yu, Sang-Hyeun; Lee, Kwang-Ho; Kang, Tae-Bong
2018-01-01
Arctium lappa (A. lappa) , Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1 β secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1 β in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa , which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.
Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation
Kim, Young-Kyu; Koppula, Sushruta; Shim, Do-Wan; In, Eun-Jung; Kwak, Su-Bin; Yu, Sang-Hyeun
2018-01-01
Arctium lappa (A. lappa), Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1β secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1β in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa, which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders. PMID:29576797
Fact Sheet: Trigeminal Neuralgia
... causes extreme, sporadic, sudden burning or shock-like facial pain that lasts anywhere from a few seconds to ... stroke, or facial trauma) may also produce neuropathic facial pain. top What are the symptoms of trigeminal neuralgia? ...
Managing Radiation Therapy Side Effects: What to Do When You Have Loose Stools (Diarrhea)
... Drink lots of clear liquids, such as water, ginger ale, and clear soup. n Most people who ... beef Drinks (clear liquids) • Clear soda, such as ginger ale • Cranberry or grape juice • Oral rehydration solution ...
Unilateral Punctate Keratitis Secondary to Wallenberg Syndrome
Boto, Ana; Del Hierro, Almudena; Capote, Maria; Noval, Susana; Garcia, Amanda; Santiago, Susana
2014-01-01
We studied three patients who developed left unilateral punctate keratitis after suffering left-sided Wallenberg Syndrome. A complex evolution occurred in two of them. In all cases, neurophysiological studies showed damage in the trigeminal sensory component at the bulbar level. Corneal involvement secondary to Wallenberg syndrome is a rare cause of unilateral superficial punctate keratitis. The loss of corneal sensitivity caused by trigeminal neuropathy leads to epithelial erosions that are frequently unobserved by the patient, resulting in a high risk of corneal-ulcer development with the possibility of superinfection. Neurophysiological studies can help to locate the anatomical level of damage at the ophthalmic branch of the trigeminal nerve, confirming the suspected etiology of stroke, and demonstrating that prior vascular involvement coincides with the location of trigeminal nerve damage. In some of these patients, oculofacial pain is a distinctive feature. PMID:24882965
Allam, Abdallah El-Sayed; Khalil, Adham Aboul Fotouh; Eltawab, Basma Aly; Wu, Wei-Ting
2018-01-01
Orofacial myofascial pain is prevalent and most often results from entrapment of branches of the trigeminal nerves. It is challenging to inject branches of the trigeminal nerve, a large portion of which are shielded by the facial bones. Bony landmarks of the cranium serve as important guides for palpation-guided injections and can be delineated using ultrasound. Ultrasound also provides real-time images of the adjacent muscles and accompanying arteries and can be used to guide the needle to the target region. Most importantly, ultrasound guidance significantly reduces the risk of collateral injury to vital neurovascular structures. In this review, we aimed to summarize the regional anatomy and ultrasound-guided injection techniques for the trigeminal nerve and its branches, including the supraorbital, infraorbital, mental, auriculotemporal, maxillary, and mandibular nerves. PMID:29808105
Botulinum toxin in trigeminal neuralgia.
Castillo-Álvarez, Federico; Hernando de la Bárcena, Ignacio; Marzo-Sola, María Eugenia
2017-01-06
Trigeminal neuralgia is one of the most disabling facial pain syndromes, with a significant impact on patients' quality of life. Pharmacotherapy is the first choice for treatment but cases of drug resistance often require new strategies, among which various interventional treatments have been used. In recent years a new therapeutic strategy consisting of botulinum toxin has emerged, with promising results. We reviewed clinical cases and case series, open-label studies and randomized clinical trials examining the use of botulinum toxin for drug-refractory trigeminal neuralgia published in the literature. The administration of botulinum toxin has proven to be a safe and effective therapeutic strategy in patients with drug-refractory idiopathic trigeminal neuralgia, but many questions remain unanswered as to the precise role of botulinum toxin in the treatment of this disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Anheim, M; Echaniz-Laguna, A; Rey, D; Tranchant, C
2006-01-01
Pure trigeminal motor neuropathy (PTMN) is a rarely described condition. We report the case of a 41-year-old woman infected with the human immunodeficiency virus (HIV1) and hepatitis C virus who presented with weakness of left temporalis and masseter muscles and painful left temporomandibular joint dysfunction (TMD) a few months after cerebral toxoplasmosis revealing acquired immunodeficiency syndrome (AIDS). Magnetic resonance imaging revealed severe wasting and fat replacement of the left temporalis, pterygoid and masseter muscles and showed neither abnormalities in the left motor nucleus of the trigeminal nerve nor compression of the left trigeminal nerve. Electromyographic examination gave evidence of denervation in the left temporalis, masseter and pterygoid muscles and blink reflex studies were normal, confirming the diagnosis of PTMN which was probably secondary to HIV and HCV co-infection.
Hegarty, Deborah M; Hermes, Sam M; Largent-Milnes, Tally M; Aicher, Sue A
2014-11-01
We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. Copyright © 2014 Elsevier B.V. All rights reserved.
Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals.
Tizzano, Marco; Gulbransen, Brian D; Vandenbeuch, Aurelie; Clapp, Tod R; Herman, Jake P; Sibhatu, Hiruy M; Churchill, Mair E A; Silver, Wayne L; Kinnamon, Sue C; Finger, Thomas E
2010-02-16
The upper respiratory tract is continually assaulted with harmful dusts and xenobiotics carried on the incoming airstream. Detection of such irritants by the trigeminal nerve evokes protective reflexes, including sneezing, apnea, and local neurogenic inflammation of the mucosa. Although free intra-epithelial nerve endings can detect certain lipophilic irritants (e.g., mints, ammonia), the epithelium also houses a population of trigeminally innervated solitary chemosensory cells (SCCs) that express T2R bitter taste receptors along with their downstream signaling components. These SCCs have been postulated to enhance the chemoresponsive capabilities of the trigeminal irritant-detection system. Here we show that transduction by the intranasal solitary chemosensory cells is necessary to evoke trigeminally mediated reflex reactions to some irritants including acyl-homoserine lactone bacterial quorum-sensing molecules, which activate the downstream signaling effectors associated with bitter taste transduction. Isolated nasal chemosensory cells respond to the classic bitter ligand denatonium as well as to the bacterial signals by increasing intracellular Ca(2+). Furthermore, these same substances evoke changes in respiration indicative of trigeminal activation. Genetic ablation of either G alpha-gustducin or TrpM5, essential elements of the T2R transduction cascade, eliminates the trigeminal response. Because acyl-homoserine lactones serve as quorum-sensing molecules for gram-negative pathogenic bacteria, detection of these substances by airway chemoreceptors offers a means by which the airway epithelium may trigger an epithelial inflammatory response before the bacteria reach population densities capable of forming destructive biofilms.
Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals
Tizzano, Marco; Gulbransen, Brian D.; Vandenbeuch, Aurelie; Clapp, Tod R.; Herman, Jake P.; Sibhatu, Hiruy M.; Churchill, Mair E. A.; Silver, Wayne L.; Kinnamon, Sue C.; Finger, Thomas E.
2010-01-01
The upper respiratory tract is continually assaulted with harmful dusts and xenobiotics carried on the incoming airstream. Detection of such irritants by the trigeminal nerve evokes protective reflexes, including sneezing, apnea, and local neurogenic inflammation of the mucosa. Although free intra-epithelial nerve endings can detect certain lipophilic irritants (e.g., mints, ammonia), the epithelium also houses a population of trigeminally innervated solitary chemosensory cells (SCCs) that express T2R bitter taste receptors along with their downstream signaling components. These SCCs have been postulated to enhance the chemoresponsive capabilities of the trigeminal irritant-detection system. Here we show that transduction by the intranasal solitary chemosensory cells is necessary to evoke trigeminally mediated reflex reactions to some irritants including acyl–homoserine lactone bacterial quorum-sensing molecules, which activate the downstream signaling effectors associated with bitter taste transduction. Isolated nasal chemosensory cells respond to the classic bitter ligand denatonium as well as to the bacterial signals by increasing intracellular Ca2+. Furthermore, these same substances evoke changes in respiration indicative of trigeminal activation. Genetic ablation of either Gα-gustducin or TrpM5, essential elements of the T2R transduction cascade, eliminates the trigeminal response. Because acyl–homoserine lactones serve as quorum-sensing molecules for Gram-negative pathogenic bacteria, detection of these substances by airway chemoreceptors offers a means by which the airway epithelium may trigger an epithelial inflammatory response before the bacteria reach population densities capable of forming destructive biofilms. PMID:20133764
Holle, Ann Van; Machado, Manuela D; Soares, Eduardo V
2012-02-01
Flocculation is an eco-friendly process of cell separation, which has been traditionally exploited by the brewing industry. Cell surface charge (CSC), cell surface hydrophobicity (CSH) and the presence of active flocculins, during the growth of two (NCYC 1195 and NCYC 1214) ale brewing flocculent strains, belonging to the NewFlo phenotype, were examined. Ale strains, in exponential phase of growth, were not flocculent and did not present active flocculent lectins on the cell surface; in contrast, the same strains, in stationary phase of growth, were highly flocculent (>98%) and presented a hydrophobicity of approximately three to seven times higher than in exponential phase. No relationship between growth phase, flocculation and CSC was observed. For comparative purposes, a constitutively flocculent strain (S646-1B) and its isogenic non-flocculent strain (S646-8D) were also used. The treatment of ale brewing and S646-1B strains with pronase E originated a loss of flocculation and a strong reduction of CSH; S646-1B pronase E-treated cells displayed a similar CSH as the non-treated S646-8D cells. The treatment of the S646-8D strain with protease did not reduce CSH. In conclusion, the increase of CSH observed at the onset of flocculation of ale strains is a consequence of the presence of flocculins on the yeast cell surface and not the cause of yeast flocculation. CSH and CSC play a minor role in the auto-aggregation of the ale strains since the degree of flocculation is defined, primarily, by the presence of active flocculins on the yeast cell wall.
Li, Huige; Xia, Ning; Brausch, Isolde; Yao, Ying; Förstermann, Ulrich
2004-09-01
Nitric oxide (NO) produced by endothelial nitric-oxide synthase (eNOS) represents an antithrombotic and anti-atherosclerotic principle in the vasculature. Hence, an enhanced expression of eNOS in response to pharmacological interventions could provide protection against cardiovascular diseases. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVECs), an artichoke leaf extract (ALE) increased the activity of the human eNOS promoter (determined by luciferase reporter gene assay). An organic subfraction from ALE was more potent in this respect than the crude extract, whereas an aqueous subfraction of ALE was without effect. ALE and the organic subfraction thereof also increased eNOS mRNA expression (measured by an RNase protection assay) and eNOS protein expression (determined by Western blot) both in EA.hy 926 cells and in native HUVECs. NO production (measured by NO-ozone chemiluminescence) was increased by both extracts. In organ chamber experiments, ex vivo incubation (18 h) of rat aortic rings with the organic subfraction of ALE enhanced the NO-mediated vasodilator response to acetylcholine, indicating that the up-regulated eNOS remained functional. Caffeoylquinic acids and flavonoids are two major groups of constituents of ALE. Interestingly, the flavonoids luteolin and cynaroside increased eNOS promoter activity and eNOS mRNA expression, whereas the caffeoylquinic acids cynarin and chlorogenic acid were without effect. Thus, in addition to the lipid-lowering and antioxidant properties of artichoke, an increase in eNOS gene transcription may also contribute to its beneficial cardiovascular profile. Artichoke flavonoids are likely to represent the active ingredients mediating eNOS up-regulation.
NASA Technical Reports Server (NTRS)
Woodruff, Kristin K.; Johnson, Anyika N.; Lee, Stuart M. C.; Gernhardt, Michael; Schneider, Suzanne M.; Foster, Philip P.
2000-01-01
Decompression sickness (DCS) is a serious risk to astronauts performing extravehicular activity (EVA). To reduce this risk, the addition of ten minutes of moderate exercise (75% VO2pk) during prebreathe has been shown to decrease the total prebreathe time from 4 to 2 hours and to decrease the incidence of DCS. The overall purpose of this pilot study was to develop an exercise protocol using flight hardware and an in-flight physical fitness cycle test to perform prebreathe exercise before an EVA. Eleven subjects volunteered to participate in this study. The first objective of this study was to compare the steady-state heart rate (HR) and oxygen consumption (VO2) from a submaximal arm and leg exercise (ALE) session with those predicted from a maximal ALE test. The second objective was to compare the steady-state HR and V02 from a submaximal elastic tube and leg exercise (TLE) session with those predicted from the maximal ALE test. The third objective involved a comparison of the maximal ALE test with a maximal leg-only (LE) test to conform to the in- flight fitness assessment test. The 75% VO2pk target HR from the LE test was significantly less than the target HR from the ALE test. Prescribing exercise using data from the maximal ALE test resulted in the measured submaximal values being higher than predicted VO2 and HR. The results of this pilot study suggest that elastic tubing is valid during EVA prebreathe as a method of arm exercise with the flight leg ergometer and it is recommended that prebreathe countermeasure exercise protocol incorporate this method.
Benlahfid, Mohammed; Erguibi, Driss; Elhattabi, Khalid; Bensardi, Fatimazahra; Khaiz, Driss; Lafriekh, Rachid; Rebroub, Dounia; Fadil, Abdelaziz; Aboussaouira, Touria
2017-01-01
Introduction La carcinose péritonéale est une diffusion inéluctablement terminale chez les patients atteints de cancers abdominaux. C'est le signe d'une maladie avancée ou d'une ré-évolution le plus souvent associée à un pronostic sombre. Environ deux tiers de l'ensemble des carcinoses péritonéales sont d'origine digestive et un tiers d'origine non digestive. Méthodes Il s'agit d'une étude rétrospective descriptive menée entre janvier 2008 et décembre 2010, dans le but de dresser le profil épidémiologique et les facteurs de risques de la carcinose péritonéale d'origine digestive au Centre Hospitalier Universitaire de Casablanca. Résultats Quarante-sept cas de carcinose péritonéale d'origine digestive ont été recensées (22 femmes, 25 hommes) ce qui représente une prévalence de 6.19% et un nombre moyen de 15.6 cas par an. L'âge était le facteur de risque essentiel dans notre série avec un âge moyen de 55.55 ans ±12.32. Les antécédents familiaux présentaient aussi un facteur de risque à prendre en considération. Conclusion A travers notre étude, nous avons conclus que les principaux facteurs de risque de la carcinose péritonéale d'origine digestive au Centre Hospitalier Universitaire Ibn Rochd Casablanca, sont l'âge et les antécédents familiaux. PMID:28979636
Surgical treatment of parapontine epidermoid cysts presenting with trigeminal neuralgia.
Guo, Zhilin; Ouyang, Huoniu; Cheng, Zhihua
2011-03-01
We retrospectively reviewed the management of 49 patients with parapontine epidermoid cyst presenting with trigeminal neuralgia, emphasizing the importance of fully removing the tumor to relieve the trigeminal neuralgia. Clinical symptoms, MRI, the operative approach, and post-operative results were examined. Trigeminal neuralgia was noted in all patients. The mean duration from onset of symptoms to surgery was 18 months. Total removal was achieved in 23 patients, near-total removal in 21, and subtotal removal in five patients. However, all tumor capsule that adhered to the trigeminal nerve was completely removed. After the operation, 33 patients developed facial hypoesthesia, three complained of double vision, and two developed acute hydrocephalus. At six months of follow-up, all patients had recovered and returned to their normal lives. At 2 years of follow-up, one patient experienced pain recurrence and underwent another operation. Parapontine epidermoid cysts either encase cranial nerve (CN) V but with intact arachnoid between the capsule and the nerve, or compress and distort the nerve with tumor capsule adherent or attached to the nerve surface. Resecting the tumor capsule's attachment to CN V is critical in relieving pain, even though this method may damage the nerve. Copyright © 2010 Elsevier Ltd. All rights reserved.
Molecular basis of tactile specialization in the duck bill.
Schneider, Eve R; Anderson, Evan O; Mastrotto, Marco; Matson, Jon D; Schulz, Vincent P; Gallagher, Patrick G; LaMotte, Robert H; Gracheva, Elena O; Bagriantsev, Sviatoslav N
2017-12-05
Tactile-foraging ducks are specialist birds known for their touch-dependent feeding behavior. They use dabbling, straining, and filtering to find edible matter in murky water, relying on the sense of touch in their bill. Here, we present the molecular characterization of embryonic duck bill, which we show contains a high density of mechanosensory corpuscles innervated by functional rapidly adapting trigeminal afferents. In contrast to chicken, a visually foraging bird, the majority of duck trigeminal neurons are mechanoreceptors that express the Piezo2 ion channel and produce slowly inactivating mechano-current before hatching. Furthermore, duck neurons have a significantly reduced mechano-activation threshold and elevated mechano-current amplitude. Cloning and electrophysiological characterization of duck Piezo2 in a heterologous expression system shows that duck Piezo2 is functionally similar to the mouse ortholog but with prolonged inactivation kinetics, particularly at positive potentials. Knockdown of Piezo2 in duck trigeminal neurons attenuates mechano current with intermediate and slow inactivation kinetics. This suggests that Piezo2 is capable of contributing to a larger range of mechano-activated currents in duck trigeminal ganglia than in mouse trigeminal ganglia. Our results provide insights into the molecular basis of mechanotransduction in a tactile-specialist vertebrate.
Molecular basis of tactile specialization in the duck bill
Anderson, Evan O.; Mastrotto, Marco; Matson, Jon D.; Schulz, Vincent P.; Gallagher, Patrick G.; LaMotte, Robert H.; Gracheva, Elena O.; Bagriantsev, Sviatoslav N.
2017-01-01
Tactile-foraging ducks are specialist birds known for their touch-dependent feeding behavior. They use dabbling, straining, and filtering to find edible matter in murky water, relying on the sense of touch in their bill. Here, we present the molecular characterization of embryonic duck bill, which we show contains a high density of mechanosensory corpuscles innervated by functional rapidly adapting trigeminal afferents. In contrast to chicken, a visually foraging bird, the majority of duck trigeminal neurons are mechanoreceptors that express the Piezo2 ion channel and produce slowly inactivating mechano-current before hatching. Furthermore, duck neurons have a significantly reduced mechano-activation threshold and elevated mechano-current amplitude. Cloning and electrophysiological characterization of duck Piezo2 in a heterologous expression system shows that duck Piezo2 is functionally similar to the mouse ortholog but with prolonged inactivation kinetics, particularly at positive potentials. Knockdown of Piezo2 in duck trigeminal neurons attenuates mechano current with intermediate and slow inactivation kinetics. This suggests that Piezo2 is capable of contributing to a larger range of mechano-activated currents in duck trigeminal ganglia than in mouse trigeminal ganglia. Our results provide insights into the molecular basis of mechanotransduction in a tactile-specialist vertebrate. PMID:29109250
47 CFR 87.149 - Special requirements for automatic link establishment (ALE).
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 5 2010-10-01 2010-10-01 false Special requirements for automatic link establishment (ALE). 87.149 Section 87.149 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Technical Requirements § 87.149 Special requirements...
Ishihara, H; San Millán Ruíz, D; Abdo, G; Asakura, F; Yilmaz, H; Lovblad, K O; Rüfenacht, D A
2011-09-01
A 32-year-old woman hospitalized for subarachnoid hemorrhage showed rare arterial variation on the right side with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. Angiography showed the right vertebral artery to originate from the right common carotid artery, the right subclavian artery to arise separately from the descending aorta, and persistent trigeminal artery on the right side. The possible embryonic mechanism of this previously unreported variant combination is discussed.
Dynamic Deployment Simulations of Inflatable Space Structures
NASA Technical Reports Server (NTRS)
Wang, John T.
2005-01-01
The feasibility of using Control Volume (CV) method and the Arbitrary Lagrangian Eulerian (ALE) method in LSDYNA to simulate the dynamic deployment of inflatable space structures is investigated. The CV and ALE methods were used to predict the inflation deployments of three folded tube configurations. The CV method was found to be a simple and computationally efficient method that may be adequate for modeling slow inflation deployment sine the inertia of the inflation gas can be neglected. The ALE method was found to be very computationally intensive since it involves the solving of three conservative equations of fluid as well as dealing with complex fluid structure interactions.
SU-F-J-160: Clinical Evaluation of Targeting Accuracy in Radiosurgery Using Tractography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Juh, R; Han, J; Kim, C
Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 males, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve. Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement. Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.« less
Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon
2015-09-01
Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they do with migraine. Copyright © 2015 Elsevier Inc. All rights reserved.
Berti, Aldo; Granville, Michelle; Jacobson, Robert E
2018-01-12
A case of an extremely healthy, active, 96-year-old patient, nonsmoker, is reviewed. He was initially treated for left V1, V2, and V3 trigeminal neuralgia in 2001, at age 80, with stereotactic radiosurgery (SRS) with a dose of 80 Gy to the left retrogasserian trigeminal nerve. He remained asymptomatic for nine years until his trigeminal pain recurred in 2010. He was first treated medically but was intolerant to increasing doses of carbamazepine and gabapentin. He underwent a second SRS in 2012 with a dose of 65.5 Gy to the same retrogasserian area of the trigeminal nerve, making the total cumulative dose 125.5 Gy. In late 2016, four years after the 2 nd SRS, he was found to have invasive keratinizing squamous cell carcinoma in the left posterior mandibular oral mucosa. Keratinizing squamous cell carcinoma is seen primarily in smokers or associated with the human papillomavirus, neither of which was found in this patient. A review of his two SRS plans shows that the left lower posterior mandibular area was clearly within the radiation fields for both SRS treatments. It is postulated that his cancer developed secondary to the long-term radiation effect with a very localized area being exposed twice to a focused, cumulative, high-dose radiation. There are individual reports in the literature of oral mucositis immediately after radiation for trigeminal neuralgia and the delayed development of malignant tumors, including glioblastoma found after SRS for acoustic neuromas, but there are no reports of delayed malignant tumors developing within the general radiation field. Using repeat SRS is an accepted treatment for recurrent trigeminal neuralgia, but physicians and patients should be aware of the potential effects of higher cumulative radiation effects within the treatment field when patients undergo repeat procedures.
SU-E-J-34: Clinical Evaluation of Targeting Accuracy and Tractogrphy Delineation of Radiosurgery
DOE Office of Scientific and Technical Information (OSTI.GOV)
Juh, R; Suh, T; Kim, Y
2014-06-01
Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 male, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve . Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.« less
Lulz, Ana Paula; Kopach, Olga; Santana-Varela, Sonia; Wood, John N
2015-01-01
Trigeminal neuralgia is accompanied by severe mechanical, thermal and chemical hypersensitivity of the orofacial area innervated by neurons of trigeminal ganglion (TG). We examined the role of the voltage-gated sodium channel subtype Nav1.9 in the development of trigeminal neuralgia. We found that Nav1.9 is required for the development of both thermal and mechanical hypersensitivity induced by constriction of the infraorbital nerve (CION). The CION model does not induce change on Nav1.9 mRNA expression in the ipsilateral TG neurons when evaluated 9 days after surgery. These results demonstrate that Nav1.9 channels play a critical role in the development of orofacial neuropathic pain. New routes for the treatment of orofacial neuropathic pain focussing on regulation of the voltage-gated Nav1.9 sodium channel activity should be investigated. © 2015 Luiz et al.
Trigeminal induced arousals during human sleep.
Heiser, Clemens; Baja, Jan; Lenz, Franziska; Sommer, J Ulrich; Hörmann, Karl; Herr, Raphael M; Stuck, Boris A
2015-05-01
Arousals caused by external stimuli during human sleep have been studied for most of the sensorial systems. It could be shown that a pure nasal trigeminal stimulus leads to arousals during sleep. The frequency of arousals increases dependent on the stimulus concentration. The aim of the study was to evaluate the influence of different stimulus durations on arousal frequency during different sleep stages. Ten young healthy volunteers with 20 nights of polysomnography were included in the study. Pure trigeminal stimulation with both different concentrations of CO2 (0, 10, 20, 40% v/v) and different stimulus durations (1, 3, 5, and 10 s) were applied during different sleep stages to the volunteers using an olfactometer. The application was performed during different sleep stages (light sleep, deep sleep, REM sleep). The number of arousals increased with rising stimulus duration and stimulus concentration during each sleep stage. Trigeminal stimuli during sleep led to arousals in dose- and time-dependent manner.
Molecular and cellular mechanisms of trigeminal chemosensation.
Gerhold, Kristin A; Bautista, Diana M
2009-07-01
Three sensory systems, olfaction, taste, and somatosensation, are dedicated to the detection of chemicals in the environment. Trigeminal somatosensory neurons enable us to detect a wide range of environmental stimuli, including pressure, temperature, and chemical irritants, within the oral and nasal mucosa. Natural plant-derived irritants have served as powerful pharmacological tools for identifying receptors underlying somatosensation. This is illustrated by the use of capsaicin, menthol, and wasabi to identify the heat-sensitive ion channel TRPV1, the cold-sensitive ion channel TRPM8, and the irritant receptor TRPA1, respectively. In addition to TRP channels, members of the two-pore potassium channel family have also been implicated in trigeminal chemosensation. KCNK18 was recently identified as a target for hydroxy-alpha-sanshool, the tingling and numbing compound produced in Schezuan peppers and other members of the Xanthoxylum genus. The role of these channels in trigeminal thermosensation and pain will be discussed.
Molecular and Cellular Mechanisms of Trigeminal Chemosensation
Gerhold, Kristin A.; Bautista, Diana M.
2010-01-01
Three sensory systems, olfaction, taste, and somatosensation, are dedicated to the detection of chemicals in the environment. Trigeminal somatosensory neurons enable us to detect a wide range of environmental stimuli, including pressure, temperature, and chemical irritants, within the oral and nasal mucosa. Natural plant-derived irritants have served as powerful pharmacological tools for identifying receptors underlying somatosensation. This is illustrated by the use of capsaicin, menthol, and wasabi to identify the heat-sensitive ion channel TRPV1, the cold-sensitive ion channel TRPM8, and the irritant receptor TRPA1, respectively. In addition to TRP channels, members of the two-pore potassium channel family have also been implicated in trigeminal chemosensation. KCNK18 was recently identified as a target for hydroxy-α-sanshool, the tingling and numbing compound produced in Schezuan peppers and other members of the Xanthoxylum genus. The role of these channels in trigeminal thermosensation and pain will be discussed. PMID:19686135
DOE Office of Scientific and Technical Information (OSTI.GOV)
Metzler, Dominik; Li, Chen; Engelmann, Sebastian
The need for atomic layer etching (ALE) is steadily increasing as smaller critical dimensions and pitches are required in device patterning. A flux-control based cyclic Ar/C 4F 8 ALE based on steady-state Ar plasma in conjunction with periodic, precise C 4F 8 injection and synchronized plasma-based low energy Ar + ion bombardment has been established for SiO 2. 1 In this work, the cyclic process is further characterized and extended to ALE of silicon under similar process conditions. The use of CHF 3 as a precursor is examined and compared to C 4F 8. CHF 3 is shown to enablemore » selective SiO 2/Si etching using a fluorocarbon (FC) film build up. Other critical process parameters investigated are the FC film thickness deposited per cycle, the ion energy, and the etch step length. Etching behavior and mechanisms are studied using in situ real time ellipsometry and X-ray photoelectron spectroscopy. Silicon ALE shows less self-limitation than silicon oxide due to higher physical sputtering rates for the maximum ion energies used in this work, ranged from 20 to 30 eV. The surface chemistry is found to contain fluorinated silicon oxide during the etching of silicon. As a result, plasma parameters during ALE are studied using a Langmuir probe and establish the impact of precursor addition on plasma properties.« less
Yi, Zhiqian; Xu, Maonian; Magnusdottir, Manuela; Zhang, Yuetuan; Brynjolfsson, Sigurdur; Fu, Weiqi
2015-09-29
Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE) was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS) was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress.
Yi, Zhiqian; Xu, Maonian; Magnusdottir, Manuela; Zhang, Yuetuan; Brynjolfsson, Sigurdur; Fu, Weiqi
2015-01-01
Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE) was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS) was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress. PMID:26426027
Phenotypic regional fMRI activation patterns during memory encoding in MCI and AD
Browndyke, Jeffrey N.; Giovanello, Kelly; Petrella, Jeffrey; Hayden, Kathleen; Chiba-Falek, Ornit; Tucker, Karen A.; Burke, James R.; Welsh-Bohmer, Kathleen A.
2014-01-01
Background Reliable blood-oxygen-level-dependent (BOLD) fMRI phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. Methods A series of random-effects, activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based upon a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. Results ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal controls across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe (MTL), specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal controls. Conclusions ALE consistencies broadly support the presence of frontal compensatory activity, MTL activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective pre-disease condition. Taken together these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD. PMID:22841497
A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization.
Akerman, Simon; Holland, Philip R; Summ, Oliver; Lasalandra, Michele P; Goadsby, Peter J
2012-12-01
Trigeminal autonomic cephalalgias are highly disabling primary headache disorders, characterized by severe unilateral head pain and associated ipsilateral cranial autonomic features. There is limited understanding of their pathophysiology and how and where treatments act to reduce symptoms; this is significantly hindered by a lack of animal models. We have developed the first animal model to explore trigeminal autonomic cephalalgias, using stimulation within the brainstem, at the level of the superior salivatory nucleus, to activate the trigeminal autonomic reflex arc. Using electrophysiological recording of neurons of the trigeminocervical complex and laser Doppler blood flow changes around the ipsilateral lacrimal duct, superior salivatory nucleus stimulation exhibited both neuronal trigeminovascular and cranial autonomic manifestations. These responses were specifically inhibited by the autonomic ganglion blocker hexamethonium bromide. These data demonstrate that brainstem activation may be the driver of both sensory and autonomic symptoms in these disorders, and part of this activation may be via the parasympathetic outflow to the cranial vasculature. Additionally, both sensory and autonomic manifestations were significantly inhibited by highly effective treatments for trigeminal autonomic cephalalgias, such as oxygen, indomethacin and triptans, and some part of their therapeutic action appears to be specifically on the parasympathetic outflow to the cranial vasculature. Treatments more used to migraine, such as naproxen and a calcitonin gene-related peptide receptor inhibitor, olcegepant, were less effective in this model. This is the first model to represent the phenotype of trigeminal autonomic cephalalgias and their response to therapies, and indicates the parasympathetic pathway may be uniquely involved in their pathophysiology and targeted to relieve symptoms.
VASS, Z.; DAI, C. F.; STEYGER, P. S.; JANCSÓ, G.; TRUNE, D. R.; NUTTALL, A. L.
2014-01-01
Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1—TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system. Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles. The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea. PMID:15026132
Cady, Ryan J.; Durham, Paul L.
2010-01-01
Activation of trigeminal nerves and release of neuropeptides that promote inflammation are implicated in the underlying pathology of migraine and temporomandibular joint (TMJ) disorders. The overall response of trigeminal nerves to peripheral inflammatory stimuli involves a balance between enzymes that promote inflammation, kinases, and those that restore homeostasis, phosphatases. The goal of this study was to determine the effects of a cocoa-enriched diet on the expression of key inflammatory proteins in trigeminal ganglion neurons under basal and inflammatory conditions. Rats were fed a control diet or an isocaloric diet enriched in cocoa for 14 days prior to an injection of noxious stimuli to cause acute or chronic excitation of trigeminal neurons. In animals fed a cocoa-enriched diet, basal levels of the mitogen-activated kinase (MAP) phosphatases MKP-1 and MKP-3 were elevated in neurons. Importantly, the stimulatory effects of acute or chronic peripheral inflammation on neuronal expression of the MAPK p38 and extracellular signal-regulated kinases (ERK) were significantly repressed in response to cocoa. Similarly, dietary cocoa significantly suppressed basal neuronal expression of calcitonin gene-related peptide (CGRP) as well as stimulated levels of the inducible form of nitric oxide synthase (iNOS), proteins implicated in the underlying pathology of migraine and TMJ disorders. To our knowledge, this is first evidence that a dietary supplement can cause upregulation of MKP, and that cocoa can prevent inflammatory responses in trigeminal ganglion neurons. Furthermore, our data provide evidence that cocoa contains biologically active compounds that would be beneficial in the treatment of migraine and TMJ disorders. PMID:20138852
Arakaki, Xianghong; McCleary, Paige; Techy, Matthew; Chiang, Jiarong; Kuo, Linus; Fonteh, Alfred N; Armstrong, Brian; Levy, Dan; Harrington, Michael G
2013-03-14
Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and -3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer.
2013-01-01
Background Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Methods Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. Results The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and −3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Conclusion Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer. PMID:23497725
Flickinger, John C; Kim, Hyun; Kano, Hideyuki; Greenberger, Joel S; Arai, Yoshio; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas; Flickinger, John C
2012-07-15
Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age ≤70 years, and Type 1 typical trigeminal neuralgia pain compared with 25% (7 of 28), 20% (23 of 114), and 33% (4 of 12) of patients taking no anticonvulsants, age >70 years, and partly atypical Type 2 trigeminal neuralgia, respectively. The use of carbamazepine or gabapentin at the time of radiosurgery does not decrease the rates of obtaining partial or complete pain relief after radiosurgery, but gabapentin may reduce the risks of developing post-radiosurgery trigeminal neuropathy. Copyright © 2012 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Flickinger, John C.; College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA; Kim, Hyun
2012-07-15
Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patientsmore » were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age {<=}70 years, and Type 1 typical trigeminal neuralgia pain compared with 25% (7 of 28), 20% (23 of 114), and 33% (4 of 12) of patients taking no anticonvulsants, age >70 years, and partly atypical Type 2 trigeminal neuralgia, respectively. Conclusions: The use of carbamazepine or gabapentin at the time of radiosurgery does not decrease the rates of obtaining partial or complete pain relief after radiosurgery, but gabapentin may reduce the risks of developing post-radiosurgery trigeminal neuropathy.« less
Unilateral or "side-locked" migrainous headache with autonomic symptoms linked to night guard use.
Strahlendorf, Jean; Schiffer, Randolph; Strahlendorf, Howard
2008-01-01
Night guards are commonly prescribed as a palliative measure for bruxism, temporomandibular joint symptoms, and associated disorders. We describe a patient with a 10- to 12-year history of night guard use with concurrent unilateral side-locked migrainous headaches with autonomic symptoms characteristic of trigeminal autonomic cephalgia. These headaches were refractory to numerous pharmacological interventions. Upon self-initiated cessation of night guard use, there was complete remission of headaches. We believe the headaches were initiated by night guard-initiated irritation of the trigeminal nerve and a trigeminal autonomic reflex resulting in unilateral migrainous headache with autonomic signs.
Bowen, Elizabeth J; Schmidt, Thomas W; Firm, Christina S; Russo, Andrew F; Durham, Paul L
2006-01-01
Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor-alpha (TNF-alpha). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNF-alpha stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNF-alpha caused a coordinate increase in CGRP promoter activity. TNF-alpha treatment activated the transcription factor NF-kappaB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNF-alpha induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels.
Bowen, Elizabeth J.; Schmidt, Thomas W.; Firm, Christina S.; Russo, Andrew F.; Durham, Paul L.
2006-01-01
Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factorα (TNFα). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNFα stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNFα caused a coordinate increase in CGRP promoter activity. TNFα treatment activated the transcription factor NF-κB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNFα induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels. PMID:16277606
Bortolami, R; Calzà, L; Lucchi, M L; Giardino, L; Callegari, E; Manni, E; Pettorossi, V E; Barazzoni, A M; Lalatta Costerbosa, G
1991-04-26
The peripheral territories of sheep trigeminal neurons which send their central process to the brainstem through the oculomotor nerve were investigated by the use of fluorescent tracers in double-labeling experiments. For this purpose Diamidino yellow (DY) injection into the oculomotor nerve was combined with Fast blue (FB) injection either into the extraocular muscles (EOMs), or the cornea, or the superior eyelid. Double-labeled DY + FB cells were found in the ophthalmic region of the trigeminal ganglion in addition to single-labeled DY or FB cells. The DY and DY + FB-labeled trigeminal cells were analysed immunocytochemically for their content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and cholecystokinin-8 (CCK-8)-like. All single-labeled DY cells showed SP-, CGRP- or CCK-8-like immunoreactivity. Double-labeled DY + FB neurons innervating the EOMs were immunoreactive for each of the three peptides, whereas double-labeled neurons supplying the cornea were only CGRP-like positive. The findings suggest that, in the sheep, trigeminal neurons which send their process centrally through the oculomotor nerve supply the EOMs, the cornea, and the superior eyelid and contain neuropeptides which are usually associated with pain sensation.
Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.
Viggiano, A; Manara, R; Conforti, R; Paccone, A; Secondulfo, C; Lorusso, L; Sbordone, L; Di Salle, F; Monda, M; Tedeschi, G; Esposito, F
2015-12-17
Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Bellamy, Jamie; Bowen, Elizabeth J.; Russo, Andrew F.; Durham, Paul L.
2006-01-01
Calcitonin gene-related peptide (CGRP) and nitric oxide are involved in the underlying pathophysiology of migraine and other diseases involving neurogenic inflammation. We have tested the hypothesis that nitric oxide might trigger signaling mechanisms within the trigeminal ganglia neurons that would coordinately stimulate CGRP synthesis and release. Treatment of primary trigeminal ganglia cultures with nitric oxide donors caused a greater than four-fold increase in CGRP release compared with unstimulated cultures. Similarly, CGRP promoter activity was also stimulated by nitric oxide donors and overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric oxide stimulation of CGRP secretion did not require cGMP or PI3-kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T-type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen-activated protein kinases Jun amino-terminal kinase and p38 but not extracellular signal-related kinase in trigeminal neurons. In summary, our results provide new insight into the cellular mechanisms by which nitric oxide induces CGRP synthesis and secretion from trigeminal neurons. PMID:16630053
Notsu, Kazuki; Tsumori, Toshiko; Yokota, Shigefumi; Sekine, Joji; Yasui, Yukihiko
2008-12-09
This study was performed to understand the anatomical substrates of hypothalamic modulation of jaw movements. After cholera toxin B subunit (CTb) injection into the parvicellular reticular formation (RFp) of the rat medulla oblongata, where many trigeminal premotor neurons have been known to exist, numerous CTb-labeled neurons were found in the posterior lateral hypothalamus (PLH) bilaterally with a clear-cut ipsilateral dominance. After ipsilateral injections of biotinylated dextran amine (BDA) into the PLH and CTb into the motor trigeminal nucleus (Vm), the prominent distribution of BDA-labeled axon terminals around CTb-labeled neurons was found in the RFp region just ventral to the nucleus of the solitary tract and medial to the spinal trigeminal nucleus ipsilateral to the injection sites. Within the neuropil of the RFp, BDA-labeled axon terminals made an asymmetrical synaptic contact predominantly with dendrites and additionally with somata of the RFp neurons, some of which were labeled with CTb. It was further revealed that these BDA-labeled axon terminals were immunoreactive for vesicular glutamate transporter 2. The present data suggest that the PLH plays an important role in the control of jaw movements by exerting its glutamatergic excitatory action upon RFp neurons presynaptic to trigeminal motoneurons.
Clinico-pathological correlation in adenylate kinase 5 autoimmune limbic encephalitis
Ng, Adeline S.L.; Kramer, Joel; Centurion, Alejandro; Dalmau, Josep; Huang, Eric; Cotter, Jennifer A.; Geschwind, Michael D.
2016-01-01
Autoantibodies associated with autoimmune limbic encephalitis (ALE) have been well-characterized, with intracellular neuronal antibodies being less responsive to immunotherapy than antibodies to cell surface antigens. Adenylate kinase 5 (AK5) is a nucleoside monophosphate kinase vital for neuronal-specific metabolism and is located intracellularly in the cytosol and expressed exclusively in the brain. Antibodies to AK5 had been previously identified but were not known to be associated with human disease prior to the report of two patients with AK5-related ALE (Tuzun et al., 2007). We present the complete clinical picture for one of these patients and the first reported neuropathology for AK5 ALE. PMID:26439959
ERIC Educational Resources Information Center
Adank, Patti
2012-01-01
The role of speech production mechanisms in difficult speech comprehension is the subject of on-going debate in speech science. Two Activation Likelihood Estimation (ALE) analyses were conducted on neuroimaging studies investigating difficult speech comprehension or speech production. Meta-analysis 1 included 10 studies contrasting comprehension…
Don't Panic! Closed String Tachyons in ALE Spacetimes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Silverstein, Eva M
2001-08-20
We consider closed string tachyons localized at the fixed points of noncompact nonsupersymmetric orbifolds. We argue that tachyon condensation drives these orbifolds to flat space or supersymmetric ALE spaces. The decay proceeds via an expanding shell of dilaton gradients and curvature which interpolates between two regions of distinct angular geometry. The string coupling remains weak throughout. For small tachyon VEVs, evidence comes from quiver theories on D-branes probes, in which deformations by twisted couplings smoothly connect non-supersymmetric orbifolds to supersymmetric orbifolds of reduced order. For large tachyon VEVs, evidence comes from worldsheet RG flow and spacetime gravity. For C{sup 2}/Z{submore » n}, we exhibit infinite sequences of transitions producing SUSY ALE spaces via twisted closed string condensation from non-supersymmetric ALE spaces. In a T-dual description this provides a mechanism for creating NS5-branes via closed string tachyon condensation similar to the creation of D-branes via open string tachyon condensation. We also apply our results to recent duality conjectures involving fluxbranes and the type 0 string.« less
Active life expectancy from annual follow-up data with missing responses.
Izmirlian, G; Brock, D; Ferrucci, L; Phillips, C
2000-03-01
Active life expectancy (ALE) at a given age is defined as the expected remaining years free of disability. In this study, three categories of health status are defined according to the ability to perform activities of daily living independently. Several studies have used increment-decrement life tables to estimate ALE, without error analysis, from only a baseline and one follow-up interview. The present work conducts an individual-level covariate analysis using a three-state Markov chain model for multiple follow-up data. Using a logistic link, the model estimates single-year transition probabilities among states of health, accounting for missing interviews. This approach has the advantages of smoothing subsequent estimates and increased power by using all follow-ups. We compute ALE and total life expectancy from these estimated single-year transition probabilities. Variance estimates are computed using the delta method. Data from the Iowa Established Population for the Epidemiologic Study of the Elderly are used to test the effects of smoking on ALE on all 5-year age groups past 65 years, controlling for sex and education.
Khattab, Hala Ah; Wazzan, Maha Am; Al-Ahdab, Maha A
2016-09-01
Nephrotoxicity represents a major health problem. This study aims to determine nephroprotective of artichoke leaves extract (ALE) against gentamicin (GM) injection in male rats. Rats (n=30) were divided into; negative control, nephrotoxic (GM) injected intraperitoneally (i.p.) with GM (100 mg/kg b.wt/d for 10 days), and groups administered orally with ALE (200, 400 or 600 mg/kg b.wt/d) and injected with GM. The results revealed that, GM injection induced marked nephrotoxicity as evidenced by significant increase in kidney functions, albumin and potassium (K+), with significant decrease in serum levels of total protein and sodium (Na + ) as compared with negative control group. There was significant increase in malondialdehyde (MDA) level in GM group compared with negative control group. Renal examined tissues showed severe changes manifested by atrophy of glomerular tuft, necrosis of epithelial lining renal tubules with apoptosis of tubular epithelium and renal hemorrhage. Simultaneous administration of ALE during GM therapy protected kidney tissues as evidenced by normalization of kidney biochemical parameters and minimized the histopathological changes. Therefore, ALE has nephroprotective and antioxidant effects, thus could be beneficial for kidney patients.
Modeling NIF experimental designs with adaptive mesh refinement and Lagrangian hydrodynamics
NASA Astrophysics Data System (ADS)
Koniges, A. E.; Anderson, R. W.; Wang, P.; Gunney, B. T. N.; Becker, R.; Eder, D. C.; MacGowan, B. J.; Schneider, M. B.
2006-06-01
Incorporation of adaptive mesh refinement (AMR) into Lagrangian hydrodynamics algorithms allows for the creation of a highly powerful simulation tool effective for complex target designs with three-dimensional structure. We are developing an advanced modeling tool that includes AMR and traditional arbitrary Lagrangian-Eulerian (ALE) techniques. Our goal is the accurate prediction of vaporization, disintegration and fragmentation in National Ignition Facility (NIF) experimental target elements. Although our focus is on minimizing the generation of shrapnel in target designs and protecting the optics, the general techniques are applicable to modern advanced targets that include three-dimensional effects such as those associated with capsule fill tubes. Several essential computations in ordinary radiation hydrodynamics need to be redesigned in order to allow for AMR to work well with ALE, including algorithms associated with radiation transport. Additionally, for our goal of predicting fragmentation, we include elastic/plastic flow into our computations. We discuss the integration of these effects into a new ALE-AMR simulation code. Applications of this newly developed modeling tool as well as traditional ALE simulations in two and three dimensions are applied to NIF early-light target designs.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Metzler, Dominik; Oehrlein, Gottlieb S., E-mail: oehrlein@umd.edu; Li, Chen
The need for atomic layer etching (ALE) is steadily increasing as smaller critical dimensions and pitches are required in device patterning. A flux-control based cyclic Ar/C{sub 4}F{sub 8} ALE based on steady-state Ar plasma in conjunction with periodic, precise C{sub 4}F{sub 8} injection and synchronized plasma-based low energy Ar{sup +} ion bombardment has been established for SiO{sub 2} [Metzler et al., J. Vac. Sci. Technol. A 32, 020603 (2014)]. In this work, the cyclic process is further characterized and extended to ALE of silicon under similar process conditions. The use of CHF{sub 3} as a precursor is examined and comparedmore » to C{sub 4}F{sub 8}. CHF{sub 3} is shown to enable selective SiO{sub 2}/Si etching using a fluorocarbon (FC) film build up. Other critical process parameters investigated are the FC film thickness deposited per cycle, the ion energy, and the etch step length. Etching behavior and mechanisms are studied using in situ real time ellipsometry and x-ray photoelectron spectroscopy. Silicon ALE shows less self-limitation than silicon oxide due to higher physical sputtering rates for the maximum ion energies used in this work, ranged from 20 to 30 eV. The surface chemistry is found to contain fluorinated silicon oxide during the etching of silicon. Plasma parameters during ALE are studied using a Langmuir probe and establish the impact of precursor addition on plasma properties.« less
Metzler, Dominik; Li, Chen; Engelmann, Sebastian; ...
2015-11-11
The need for atomic layer etching (ALE) is steadily increasing as smaller critical dimensions and pitches are required in device patterning. A flux-control based cyclic Ar/C 4F 8 ALE based on steady-state Ar plasma in conjunction with periodic, precise C 4F 8 injection and synchronized plasma-based low energy Ar + ion bombardment has been established for SiO 2. 1 In this work, the cyclic process is further characterized and extended to ALE of silicon under similar process conditions. The use of CHF 3 as a precursor is examined and compared to C 4F 8. CHF 3 is shown to enablemore » selective SiO 2/Si etching using a fluorocarbon (FC) film build up. Other critical process parameters investigated are the FC film thickness deposited per cycle, the ion energy, and the etch step length. Etching behavior and mechanisms are studied using in situ real time ellipsometry and X-ray photoelectron spectroscopy. Silicon ALE shows less self-limitation than silicon oxide due to higher physical sputtering rates for the maximum ion energies used in this work, ranged from 20 to 30 eV. The surface chemistry is found to contain fluorinated silicon oxide during the etching of silicon. As a result, plasma parameters during ALE are studied using a Langmuir probe and establish the impact of precursor addition on plasma properties.« less
Yun, Chanyong; Jung, Youngchul; Chun, Wonjoo; Yang, Beodeul; Ryu, Junghyun; Lim, Chiyeon; Kim, Jung-Hoon; Kim, Hyungwoo; Cho, Su-In
2016-01-01
The leaves of Artemisia argyi Lev. et Vant. and A. princeps Pamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects of Artemisia leaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2 (PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2 in Raw 264.7 cells. These results indicate that Artemisia leaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues.
Yun, Chanyong; Jung, Youngchul; Chun, Wonjoo; Yang, Beodeul; Ryu, Junghyun; Cho, Su-In
2016-01-01
The leaves of Artemisia argyi Lev. et Vant. and A. princeps Pamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects of Artemisia leaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2 (PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2 in Raw 264.7 cells. These results indicate that Artemisia leaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues. PMID:27647952
Capuano, Alessandro; Greco, Maria Cristina; Navarra, Pierluigi; Tringali, Giuseppe
2014-10-05
The neural mechanism(s) underlying migraine remain poorly defined at present; preclinical and clinical studies show an involvement of CGRP in this disorder. However current evidence pointed out that CGRP does not exert an algogenic action per se, but it is able to mediate migraine pain only if the trigeminal-vascular system is sensitized. The present study was addressed to investigate CGRP-evoked behavior in nitric oxide (NO) sensitized rats, using an experimental model of nitroglycerin induced sensitization of trigeminal system, looking at neuropeptide release from different cerebral areas after the intra-peritoneal (i.p.) administration of NO-donors. CGRP injected into the rat whisker pad did not induce significant changes in face rubbing behavior compared to controls. On the contrary, CGRP injected in animals pre-treated with 10mg/kg nitroglycerin significantly increased the time spent in face rubbing. Nitroglycerin pre-treated animals did not show any rubbing behavior after locally injected saline. Furthermore, the i.p. treatment with nitroglycerin produced an increase of CGRP levels in brainstem and trigeminal ganglia, but not in the hypothalamus and hippocampus. The absolute amounts of CGRP produced in the brainstem were lower compared to those in the trigeminal ganglion; however, after nitroglycerin stimulation the percentage increase was higher in the brainstem. In conclusion, findings presented in this study suggest that CGRP induces a painful behavior in rats only after sensitization of trigeminal system; thus supporting the concept that a genetic as well as acquired predisposition to trigemino- vascular activation represents the neurobiological basis of CGRP nociceptive effects in migraineurs. Copyright © 2014 Elsevier B.V. All rights reserved.
Ling, Jennifer; Erol, Ferhat; Viatchenko-Karpinski, Viacheslav; Kanda, Hirosato; Gu, Jianguo G
2017-01-01
Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a dose-limiting side effect in cancer treatment. The mechanisms underlying chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels are low-threshold voltage-gated K+ channels that play a role in controlling neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be an underlying mechanism of sensory hypersensitivity that leads to neuropathic pain. However, it is currently unknown whether KCNQ channels may be downregulated by chemotherapy drugs in trigeminal ganglion neurons to contribute to the pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present study, mechanical sensitivity in orofacial regions is measured using the operant behavioral test in rats treated with oxaliplatin. Operant behaviors in these animals show the gradual development of orofacial neuropathic pain that manifests with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2 immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are significantly reduced in oxaliplatin-treated animals. Immunostaining is also performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc) in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in oxaliplatin-treated animals. We further show with the operant behavioral test that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2 downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain and KCNQ2 potentiators may be useful for alleviating the neuropathic pain.
SU-E-T-669: Radiosurgery Failure for Trigeminal Neuralgia: A Study of Radiographic Spatial Fidelity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Howe, J; Spalding, A
Purpose: Management of Trigeminal Neuralgia with radiosurgery is well established, but often met with limited success. Recent advancements in imaging afford improvements in target localization for radiosurgery. Methods: A Trigeminal Neuralgia radiosurgery specific protocol was established for MR enhancement of the trigeminal nerve using a CISS scan with slice spacing of 0.7mm. Computed Tomography simulation was performed using axial slices on a 40 slice CT with slice spacing of 0.6mm. These datasets were registered using a mutual information algorithm and localized in a stereotactic coordinate system. Image registration between the MR and CT was evaluated for each patient by amore » Medical Physicist to ensure accuracy. The dorsal root entry zone target was defined on the CISS MR by a Neurosurgeon and dose calculations performed on the localized CT. Treatment plans were reviewed and approved by a Radiation Oncologist and Neurosurgeon. Image guided radiosurgery was delivered using positioning tolerance of 0.5mm and 1°. Eight patients with Trigeminal Neuralgia were treated with this protocol. Results: Seven patients reported a favorable response to treatment with average Barrow Neurological Index pain score of four before treatment and one following treatment. Only one patient had a BNI>1 following treatment and review of the treatment plan revealed that the CISS MR was registered to the CT via a low resolution (5mm slice spacing) T2 MR. All other patients had CISS MR registered directly with the localized CT. This patient was retreated 6 months later using direct registration between CISS MR and localized CT and subsequently responded to treatment with a BNI of one. Conclusion: Frameless radiosurgery offers an effective solution to Trigeminal Neuralgia management provided appropriate technology and imaging protocols (utilizing submillimeter imaging) are established and maintained.« less
Magnetic field changes activate the trigeminal brainstem complex in a migratory bird
Heyers, Dominik; Zapka, Manuela; Hoffmeister, Mara; Wild, John Martin; Mouritsen, Henrik
2010-01-01
The upper beak of birds, which contains putative magnetosensory ferro-magnetic structures, is innervated by the ophthalmic branch of the trigeminal nerve (V1). However, because of the absence of replicable neurobiological evidence, a general acceptance of the involvement of the trigeminal nerve in magnetoreception is lacking in birds. Using an antibody to ZENK protein to indicate neuronal activation, we here document reliable magnetic activation of neurons in and near the principal (PrV) and spinal tract (SpV) nuclei of the trigeminal brainstem complex, which represent the two brain regions known to receive primary input from the trigeminal nerve. Significantly more neurons were activated in PrV and in medial SpV when European robins (Erithacus rubecula) experienced a magnetic field changing every 30 seconds for a period of 3 h (CMF) than when robins experienced a compensated, zero magnetic field condition (ZMF). No such differences in numbers of activated neurons were found in comparison structures. Under CMF conditions, sectioning of V1 significantly reduced the number of activated neurons in and near PrV and medial SpV, but not in lateral SpV or in the optic tectum. Tract tracing of V1 showed spatial proximity and regional overlap of V1 nerve endings and ZENK-positive (activated) neurons in SpV, and partly in PrV, under CMF conditions. Together, these results suggest that magnetic field changes activate neurons in and near the trigeminal brainstem complex and that V1 is necessary for this activation. We therefore suggest that V1 transmits magnetic information to the brain in this migratory passerine bird. PMID:20439705
Zakharov, A.; Vitale, C.; Kilinc, E.; Koroleva, K.; Fayuk, D.; Shelukhina, I.; Naumenko, N.; Skorinkin, A.; Khazipov, R.; Giniatullin, R.
2015-01-01
Trigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters) were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish “responder” (65%) from “non-responder” clusters (35%). Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at brainstem and spinal cord level. Almost all spikes were suppressed by tetrodotoxin (TTX) suggesting an involvement of the TTX-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing) and long-lasting (slowly desensitizing) responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine. PMID:26283923
Hung, Peter S-P; Chen, David Q; Davis, Karen D; Zhong, Jidan; Hodaie, Mojgan
2017-01-01
Trigeminal neuralgia (TN) is a chronic neuropathic facial pain disorder that commonly responds to surgery. A proportion of patients, however, do not benefit and suffer ongoing pain. There are currently no imaging tools that permit the prediction of treatment response. To address this paucity, we used diffusion tensor imaging (DTI) to determine whether pre-surgical trigeminal nerve microstructural diffusivities can prognosticate response to TN treatment. In 31 TN patients and 16 healthy controls, multi-tensor tractography was used to extract DTI-derived metrics-axial (AD), radial (RD), mean diffusivity (MD), and fractional anisotropy (FA)-from the cisternal segment, root entry zone and pontine segment of trigeminal nerves for false discovery rate-corrected Student's t -tests. Ipsilateral diffusivities were bootstrap resampled to visualize group-level diffusivity thresholds of long-term response. To obtain an individual-level statistical classifier of surgical response, we conducted discriminant function analysis (DFA) with the type of surgery chosen alongside ipsilateral measurements and ipsilateral/contralateral ratios of AD and RD from all regions of interest as prediction variables. Abnormal diffusivity in the trigeminal pontine fibers, demonstrated by increased AD, highlighted non-responders (n = 14) compared to controls. Bootstrap resampling revealed three ipsilateral diffusivity thresholds of response-pontine AD, MD, cisternal FA-separating 85% of non-responders from responders. DFA produced an 83.9% (71.0% using leave-one-out-cross-validation) accurate prognosticator of response that successfully identified 12/14 non-responders. Our study demonstrates that pre-surgical DTI metrics can serve as a highly predictive, individualized tool to prognosticate surgical response. We further highlight abnormal pontine segment diffusivities as key features of treatment non-response and confirm the axiom that central pain does not commonly benefit from peripheral treatments.
Weon, Haein; Kim, Tae Wan; Youn, Dong-Ho
2017-11-01
Both N-type and P/Q-type voltage-gated Ca 2+ channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs). (S)-3,5-Dihydroxyphenylglycine (DHPG; 10μM for 5min), the group I mGluR agonist, was used to induce LTP of excitatory postsynaptic currents that were evoked in the Vo neurons by stimulating the trigeminal track. Weak blockade of the N-type or P/Q-type VGCCs by ω-conotoxin GVIA or ω-agatoxin IVA, respectively, which inhibited only 20-40% of Ca 2+ currents recorded in isolated trigeminal ganglion neurons but had no effect on the basal excitatory synaptic transmission, completely blocked the induction of LTP. In contrast, stronger blockade of the channels, which inhibited >50% of Ca 2+ currents and about 30% of basal synaptic transmission, resulted in the development of long-term depression (LTD), the long-lasting decrease of synaptic strength. Interestingly, the postsynaptic mechanism of DHPG-induced LTP, which was determined by paired-pulse ratio, disappeared when LTP was blocked, or LTD occurred, while a presynaptic mechanism still remained. Our data suggest that postsynaptic N-type and P/Q-type VGCCs mediate the DHPG-induced LTP at the trigeminal afferent synapses in the Vo. Copyright © 2017 Elsevier Inc. All rights reserved.
Efficient Exploration of the Space of Reconciled Gene Trees
Szöllősi, Gergely J.; Rosikiewicz, Wojciech; Boussau, Bastien; Tannier, Eric; Daubin, Vincent
2013-01-01
Gene trees record the combination of gene-level events, such as duplication, transfer and loss (DTL), and species-level events, such as speciation and extinction. Gene tree–species tree reconciliation methods model these processes by drawing gene trees into the species tree using a series of gene and species-level events. The reconstruction of gene trees based on sequence alone almost always involves choosing between statistically equivalent or weakly distinguishable relationships that could be much better resolved based on a putative species tree. To exploit this potential for accurate reconstruction of gene trees, the space of reconciled gene trees must be explored according to a joint model of sequence evolution and gene tree–species tree reconciliation. Here we present amalgamated likelihood estimation (ALE), a probabilistic approach to exhaustively explore all reconciled gene trees that can be amalgamated as a combination of clades observed in a sample of gene trees. We implement the ALE approach in the context of a reconciliation model (Szöllősi et al. 2013), which allows for the DTL of genes. We use ALE to efficiently approximate the sum of the joint likelihood over amalgamations and to find the reconciled gene tree that maximizes the joint likelihood among all such trees. We demonstrate using simulations that gene trees reconstructed using the joint likelihood are substantially more accurate than those reconstructed using sequence alone. Using realistic gene tree topologies, branch lengths, and alignment sizes, we demonstrate that ALE produces more accurate gene trees even if the model of sequence evolution is greatly simplified. Finally, examining 1099 gene families from 36 cyanobacterial genomes we find that joint likelihood-based inference results in a striking reduction in apparent phylogenetic discord, with respectively. 24%, 59%, and 46% reductions in the mean numbers of duplications, transfers, and losses per gene family. The open source implementation of ALE is available from https://github.com/ssolo/ALE.git. [amalgamation; gene tree reconciliation; gene tree reconstruction; lateral gene transfer; phylogeny.] PMID:23925510
de OLIVEIRA, Danila; HASSUMI, Jaqueline Suemi; GOMES-FERREIRA, Pedro Henrique da Silva; POLO, Tárik Ocon Braga; FERREIRA, Gabriel Ramalho; FAVERANI, Leonardo Perez; OKAMOTO, Roberta
2017-01-01
Abstract Sodium alendronate is a bisphosphonate drug that exerts antiresorptive action and is used to treat osteoporosis. Objective The aim of this study was to evaluate the bone repair process at the bone/implant interface of osteoporotic rats treated with sodium alendronate through the analysis of microtomography, real time polymerase chain reactions and immunohistochemistry (RUNX2 protein, bone sialoprotein (BSP), alkaline phosphatase, osteopontin and osteocalcin). Material and Methods A total of 42 rats were used and divided in to the following experimental groups: CTL: control group (rats submitted to fictitious surgery and fed with a balanced diet), OST: osteoporosis group (rats submitted to a bilateral ovariectomy and fed with a low calcium diet) and ALE: alendronate group (rats submitted to a bilateral ovariectomy, fed with a low calcium diet and treated with sodium alendronate). A surface treated implant was installed in both tibial metaphyses of each rat. Euthanasia of the animals was conducted at 14 (immunhostochemistry) and 42 days (immunohistochemistry, micro CT and PCR). Data were subjected to statistical analysis with a 5% significance level. Results Bone volume (BV) and total pore volume were higher for ALE group (P<0.05). Molecular data for RUNX2 and BSP proteins were significantly expressed in the ALE group (P<0.05), in comparison with the other groups. ALP expression was higher in the CTL group (P<0.05). The immunostaining for RUNX2 and osteopontin was positive in the osteoblastic lineage cells of neoformed bone for the CTL and ALE groups in both periods (14 and 42 days). Alkaline phosphatase presented a lower staining area in the OST group compared to the CTL in both periods and the ALE at 42 days. Conclusion There was a decrease of osteocalcin precipitation at 42 days for the ALE and OST groups. Therefore, treatment with short-term sodium alendronate improved bone repair around the implants installed in the tibia of osteoporotic rats. PMID:28198975
Modeling Three-Dimensional Shock Initiation of PBX 9501 in ALE3D
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leininger, L; Springer, H K; Mace, J
A recent SMIS (Specific Munitions Impact Scenario) experimental series performed at Los Alamos National Laboratory has provided 3-dimensional shock initiation behavior of the HMX-based heterogeneous high explosive, PBX 9501. A series of finite element impact calculations have been performed in the ALE3D [1] hydrodynamic code and compared to the SMIS results to validate and study code predictions. These SMIS tests used a powder gun to shoot scaled NATO standard fragments into a cylinder of PBX 9501, which has a PMMA case and a steel impact cover. This SMIS real-world shot scenario creates a unique test-bed because (1) SMIS tests facilitatemore » the investigation of 3D Shock to Detonation Transition (SDT) within the context of a considerable suite of diagnostics, and (2) many of the fragments arrive at the impact plate off-center and at an angle of impact. A particular goal of these model validation experiments is to demonstrate the predictive capability of the ALE3D implementation of the Tarver-Lee Ignition and Growth reactive flow model [2] within a fully 3-dimensional regime of SDT. The 3-dimensional Arbitrary Lagrange Eulerian (ALE) hydrodynamic model in ALE3D applies the Ignition and Growth (I&G) reactive flow model with PBX 9501 parameters derived from historical 1-dimensional experimental data. The model includes the off-center and angle of impact variations seen in the experiments. Qualitatively, the ALE3D I&G calculations reproduce observed 'Go/No-Go' 3D Shock to Detonation Transition (SDT) reaction in the explosive, as well as the case expansion recorded by a high-speed optical camera. Quantitatively, the calculations show good agreement with the shock time of arrival at internal and external diagnostic pins. This exercise demonstrates the utility of the Ignition and Growth model applied for the response of heterogeneous high explosives in the SDT regime.« less
NASA Astrophysics Data System (ADS)
DuMont, Jaime Willadean
In this thesis, in situ Fourier transform infrared (FTIR) spectroscopy was used to study: i) the growth and pyrolysis of molecular layer deposition (MLD) films. ii) the surface chemistry of atomic layer etching (ALE) processes. Atomic layer processes such as molecular layer deposition (MLD) and atomic layer etching (ALE) are techniques that can add or remove material with atomic level precision using sequential, self-limiting surface reactions. Deposition and removal processes at the atomic scale are powerful tools for many industrial and research applications such as energy storage and semiconductor nanofabrication. The first section of this thesis describes the chemistry of reactions leading to the MLD of aluminum and tin alkoxide polymer films known as "alucone" and "tincone", respectively. The subsequent pyrolysis of these films to produce metal oxide/carbon composites was also investigated. In situ FTIR spectroscopy was conducted to monitor surface species during MLD film growth and to monitor the films background infrared absorbance versus pyrolysis temperature. Ex situ techniques such as transmission electron microscopy (TEM), four-point probe and X-ray diffraction (XRD) were utilized to study the properties of the films post-pyrolysis. TEM confirmed that the pyrolyzed films maintained conformality during post-processing. Four-point probe monitored film resistivity versus pyrolysis temperature and XRD determined the film crystallinity. The second section of this thesis focuses on the surface chemistry of Al2O3 and SiO2 ALE processes, respectively. Thermal ALE processes have been recently developed which utilize sequential fluorination and ligand exchange reactions. An intimate knowledge of the surface chemistry is important in understanding the ALE process. In this section, the competition between the Al2O3 etching and AlF 3 growth that occur during sequential HF (fluorinating agent) and TMA (ligand exchange) exposures is investigated using in situ FTIR spectroscopy. Also included in this section is the first demonstration of thermal ALE for SiO2. In situ FTIR spectroscopy was conducted to monitor the loss of bulk Si-O vibrational modes corresponding to the removal of SiO2. FTIR was also used to monitor surface species during each ALE half cycle and to verify self-limiting behavior. X-ray reflectivity experiments were conducted to establish etch rates on thermal oxide silicon wafers.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Chen; Metzler, Dominik; Oehrlein, Gottlieb S., E-mail: oehrlein@umd.edu
Angstrom-level plasma etching precision is required for semiconductor manufacturing of sub-10 nm critical dimension features. Atomic layer etching (ALE), achieved by a series of self-limited cycles, can precisely control etching depths by limiting the amount of chemical reactant available at the surface. Recently, SiO{sub 2} ALE has been achieved by deposition of a thin (several Angstroms) reactive fluorocarbon (FC) layer on the material surface using controlled FC precursor flow and subsequent low energy Ar{sup +} ion bombardment in a cyclic fashion. Low energy ion bombardment is used to remove the FC layer along with a limited amount of SiO{sub 2} frommore » the surface. In the present article, the authors describe controlled etching of Si{sub 3}N{sub 4} and SiO{sub 2} layers of one to several Angstroms using this cyclic ALE approach. Si{sub 3}N{sub 4} etching and etching selectivity of SiO{sub 2} over Si{sub 3}N{sub 4} were studied and evaluated with regard to the dependence on maximum ion energy, etching step length (ESL), FC surface coverage, and precursor selection. Surface chemistries of Si{sub 3}N{sub 4} were investigated by x-ray photoelectron spectroscopy (XPS) after vacuum transfer at each stage of the ALE process. Since Si{sub 3}N{sub 4} has a lower physical sputtering energy threshold than SiO{sub 2}, Si{sub 3}N{sub 4} physical sputtering can take place after removal of chemical etchant at the end of each cycle for relatively high ion energies. Si{sub 3}N{sub 4} to SiO{sub 2} ALE etching selectivity was observed for these FC depleted conditions. By optimization of the ALE process parameters, e.g., low ion energies, short ESLs, and/or high FC film deposition per cycle, highly selective SiO{sub 2} to Si{sub 3}N{sub 4} etching can be achieved for FC accumulation conditions, where FC can be selectively accumulated on Si{sub 3}N{sub 4} surfaces. This highly selective etching is explained by a lower carbon consumption of Si{sub 3}N{sub 4} as compared to SiO{sub 2}. The comparison of C{sub 4}F{sub 8} and CHF{sub 3} only showed a difference in etching selectivity for FC depleted conditions. For FC accumulation conditions, precursor chemistry has a weak impact on etching selectivity. Surface chemistry analysis shows that surface fluorination and FC reduction take place during a single ALE cycle for FC depleted conditions. A fluorine rich carbon layer was observed on the Si{sub 3}N{sub 4} surface after ALE processes for which FC accumulation takes place. The angle resolved-XPS thickness calculations confirmed the results of the ellipsometry measurements in all cases.« less
AlMasri, Omar A; Brown, Emma E; Forster, Alan; Kamel, Mahmoud H
2014-11-01
The aim in this paper was to localize and detect incipient damage to the ophthalmic and maxillary branches of the trigeminal nerve during tumor surgery. This was an observational study of patients with skull base, retroorbital, or cavernous sinus tumors warranting dissection toward the cavernous sinus at a university hospital. Stimuli were applied as normal during approach to the cavernous sinus to localize cranial nerves (CNs) III, IV, and VI. Recordings were also obtained from the facial muscles to localize CN VII. The trigeminofacial reflex was sought simply by observing a longer time base routinely. Clear facial electromyography responses were reproduced when stimuli were applied to the region of V1, V2, and V3. Response latency was increased compared with direct CN VII stimuli seen in some cases. Responses gave early warning of approach to these sensory trigeminal branches. The authors submit this as a new technique, which may improve the chances of preserving trigeminal sensory branches during surgery in this region.
Sleep disorders and chronic craniofacial pain: Characteristics and management possibilities.
Almoznino, Galit; Benoliel, Rafael; Sharav, Yair; Haviv, Yaron
2017-06-01
Chronic craniofacial pain involves the head, face and oral cavity and is associated with significant morbidity and high levels of health care utilization. A bidirectional relationship is suggested in the literature for poor sleep and pain, and craniofacial pain and sleep are reciprocally related. We review this relationship and discuss management options. Part I reviews the relationship between pain and sleep disorders in the context of four diagnostic categories of chronic craniofacial pain: 1) primary headaches: migraines, tension-type headache (TTH), trigeminal autonomic cephalalgias (TACs) and hypnic headache, 2) secondary headaches: sleep apnea headache, 3) temporomandibular joint disorders (TMD) and 4) painful cranial neuropathies: trigeminal neuralgia, post-herpetic trigeminal neuropathy, painful post-traumatic trigeminal neuropathy (PTTN) and burning mouth syndrome (BMS). Part II discusses the management of patients with chronic craniofacial pain and sleep disorders addressing the factors that modulate the pain experience as well as sleep disorders and including both non-pharmacological and pharmacological modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.
Orofacial pain management: current perspectives.
Romero-Reyes, Marcela; Uyanik, James M
2014-01-01
Some of the most prevalent and debilitating pain conditions arise from the structures innervated by the trigeminal system (head, face, masticatory musculature, temporomandibular joint and associated structures). Orofacial pain (OFP) can arise from different regions and etiologies. Temporomandibular disorders (TMD) are the most prevalent orofacial pain conditions for which patients seek treatment. Temporomandibular disorders include a number of clinical problems that involve the masticatory musculature, the temporomandibular joint (TMJ) or both. Trigeminal neuropathic pain conditions can arise from injury secondary to dental procedures, infection, neoplasias, or disease or dysfunction of the peripheral and/or central nervous system. Neurovascular disorders, such as primary headaches, can present as chronic orofacial pain, such as in the case of facial migraine, where the pain is localized in the second and third division of the trigeminal nerve. Together, these disorders of the trigeminal system impact the quality of life of the sufferer dramatically. A multidisciplinary pain management approach should be considered for the optimal treatment of orofacial pain disorders including both non-pharmacological and pharmacological modalities.
Orofacial pain management: current perspectives
Romero-Reyes, Marcela; Uyanik, James M
2014-01-01
Some of the most prevalent and debilitating pain conditions arise from the structures innervated by the trigeminal system (head, face, masticatory musculature, temporomandibular joint and associated structures). Orofacial pain (OFP) can arise from different regions and etiologies. Temporomandibular disorders (TMD) are the most prevalent orofacial pain conditions for which patients seek treatment. Temporomandibular disorders include a number of clinical problems that involve the masticatory musculature, the temporomandibular joint (TMJ) or both. Trigeminal neuropathic pain conditions can arise from injury secondary to dental procedures, infection, neoplasias, or disease or dysfunction of the peripheral and/or central nervous system. Neurovascular disorders, such as primary headaches, can present as chronic orofacial pain, such as in the case of facial migraine, where the pain is localized in the second and third division of the trigeminal nerve. Together, these disorders of the trigeminal system impact the quality of life of the sufferer dramatically. A multidisciplinary pain management approach should be considered for the optimal treatment of orofacial pain disorders including both non-pharmacological and pharmacological modalities. PMID:24591846
Khan, Mohammad; Nishi, Shamima Easmin; Hassan, Siti Nazihahasma; Islam, Md Asiful; Gan, Siew Hua
2017-01-01
Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome.
Nishi, Shamima Easmin; Hassan, Siti Nazihahasma
2017-01-01
Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome. PMID:28827979
[Trigeminal motor paralysis and dislocation of the temporo-mandibular joints].
Ohkawa, S; Yoshida, T; Ohsumi, Y; Tabuchi, M
1996-07-01
A 64-year-old woman with diabetes mellitus was admitted to our hospital with left hemiparesis of sudden onset. A brain MRI demonstrated a cerebral infarction in the ventral part of the right lower pons. When left hemiparesis worsened, she had dislocation of the temporo-mandibular joints repeatedly. Then, her lower jaw deviated to the right when she opened her mouth. Also, there was decreased contraction of the right masseter when she clenched her teeth. These findings suggest that there was trigeminal motor paralysis on the right side resulting from involvement of the intrapontine trigeminal motor nerve. She has no history of dislocation of the temporo-mandibular joints. An X-ray film showed that the temporo-mandibular joints were intact. Thus, it is possible that deviation of the lower jaw was the cause of this dislocation. We suspect that dislocation of the temporo-mandibular joints may occur as a complication of unilateral trigeminal motor paralysis. This has not been reported to our knowledge.
Schwend, Tyler; Lwigale, Peter Y.; Conrad, Gary W.
2012-01-01
The cornea, the most densely innervated tissue on the surface of the body, becomes innervated in a series of highly coordinated developmental events. During cornea development, chick trigeminal nerve growth cones reach the cornea margin at embryonic day (E)5, where they are initially repelled for days from E5-8, instead encircling the corneal periphery in a nerve ring prior to entering on E9. The molecular events coordinating growth cone guidance during cornea development are poorly understood. Here we evaluated a potential role for the Robo-Slit nerve guidance family. We found that Slit 1, 2 and 3 expression in the cornea and lens persisted during all stages of cornea innervation examined. Robo1 expression was developmentally regulated in trigeminal cell bodies, expressed robustly during nerve ring formation (E5-8), then later declining concurrent with projection of growth cones into the cornea. In this study we provide in vivo and in vitro evidence that Robo-Slit signaling guides trigeminal nerves during cornea innervation. Transient, localized inhibition of Robo-Slit signaling, by means of beads loaded with inhibitory Robo-Fc protein implanted into the developing eyefield in vivo, led to disorganized nerve ring formation and premature cornea innervation. Additionally, when trigeminal explants (source of neurons) were oriented adjacent to lens vesicles or corneas (source of repellant molecules) in organotypic tissue culture both lens and cornea tissues strongly repelled E7 trigeminal neurites, except in the presence of inhibitory Robo-Fc protein. In contrast, E10 trigeminal neurites were not as strongly repelled by cornea, and presence of Robo-Slit inhibitory protein had no effect. In full, these findings suggest that nerve repulsion from the lens and cornea during nerve ring formation is mediated by Robo-Slit signaling. Later, a shift in nerve guidance behavior occurs, in part due to molecular changes in trigeminal neurons, including Robo1 downregulation, thus allowing nerves to find the Slit-expressing cornea permissive for growth cones. PMID:22236962
Wu, Min; Fu, Xianming; Ji, Ying; Ding, Wanhai; Deng, Dali; Wang, Yehan; Jiang, Xiaofeng; Niu, Chaoshi
2018-05-01
Microvascular decompression of the trigeminal nerve is the most effective treatment for trigeminal neuralgia. However, when encountering classical trigeminal neuralgia caused by venous compression, the procedure becomes much more difficult, and failure or recurrence because of incomplete decompression may become frequent. This study aimed to investigate the anatomic variation of the culprit veins and discuss the surgical strategy for different types. We performed a retrospective analysis of 64 consecutive cases in whom veins were considered as responsible vessels alone or combined with other adjacent arteries. The study classified culprit veins according to operative anatomy and designed personalized approaches and decompression management according to different forms of compressive veins. Curative effects were assessed by the Barrow Neurological Institute (BNI) pain intensity score and BNI facial numbness score. The most commonly encountered veins were the superior petrosal venous complex (SPVC), which was artificially divided into 4 types according to both venous tributary distribution and empty point site. We synthetically considered these factors and selected an approach to expose the trigeminal root entry zone, including the suprafloccular transhorizontal fissure approach and infratentorial supracerebellar approach. The methods of decompression consist of interposing and transposing by using Teflon, and sometimes with the aid of medical adhesive. Nerve combing (NC) of the trigeminal root was conducted in situations of extremely difficult neurovascular compression, instead of sacrificing veins. Pain completely disappeared in 51 patients, and the excellent outcome rate was 79.7%. There were 13 patients with pain relief treated with reoperation. Postoperative complications included 10 cases of facial numbness, 1 case of intracranial infection, and 1 case of high-frequency hearing loss. The accuracy recognition of anatomic variation of the SPVC is crucial for the management of classical trigeminal neuralgia caused by venous compression. Selecting an appropriate approach and using reasonable decompression methods can bring complete postoperative pain relief for most cases. NC can be an alternative choice for extremely difficult cases, but it could lead to facial numbness more frequently. Copyright © 2018 Elsevier Inc. All rights reserved.
Nakaya, Yuka; Tsuboi, Yoshiyuki; Okada-Ogawa, Akiko; Shinoda, Masamichi; Kubo, Asako; Chen, Jui Yen; Noma, Noboru; Batbold, Dulguun; Imamura, Yoshiki; Sessle, Barry J; Iwata, Koichi
2016-01-01
Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats. These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying. © The Author(s) 2016.
Glendinning, John I; Tang, Joyce; Morales Allende, Ana Paula; Bryant, Bruce P; Youngentob, Lisa; Youngentob, Steven L
2017-08-01
Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes. NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal chemosensory neurons. We found that FAE substantially reduced taste and trigeminal responsiveness to ethanol and its flavor components. Copyright © 2017 the American Physiological Society.
Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N. B.; Hummel, Thomas
2011-01-01
Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality. PMID:21556139
Croy, Ilona; Springborn, Maria; Lötsch, Jörn; Johnston, Amy N B; Hummel, Thomas
2011-04-27
Correlations between personality traits and a wide range of sensory thresholds were examined. Participants (N = 124) completed a personality inventory (NEO-FFI) and underwent assessment of olfactory, trigeminal, tactile and gustatory detection thresholds, as well as examination of trigeminal and tactile pain thresholds. Significantly enhanced odor sensitivity in socially agreeable people, significantly enhanced trigeminal sensitivity in neurotic subjects, and a tendency for enhanced pain tolerance in highly conscientious participants was revealed. It is postulated that varied sensory processing may influence an individual's perception of the environment; particularly their perception of socially relevant or potentially dangerous stimuli and thus, varied with personality.
Trigeminal Neuralgia and Multiple Sclerosis: A Historical Perspective.
Burkholder, David B; Koehler, Peter J; Boes, Christopher J
2017-09-01
Trigeminal neuralgia (TN) associated with multiple sclerosis (MS) was first described in Lehrbuch der Nervenkrankheiten für Ärzte und Studirende in 1894 by Hermann Oppenheim, including a pathologic description of trigeminal root entry zone demyelination. Early English-language translations in 1900 and 1904 did not so explicitly state this association compared with the German editions. The 1911 English-language translation described a more direct association. Other later descriptions were clinical with few pathologic reports, often referencing Oppenheim but citing the 1905 German or 1911 English editions of Lehrbuch. This discrepancy in part may be due to the translation differences of the original text.
Trigeminal autonomic cephalgias
2012-01-01
Summary points 1. Trigeminal autonomic cephalgias (TACs) are headaches/facial pains classified together based on:a suspected common pathophysiology involving the trigeminovascular system, the trigeminoparasympathetic reflex and centres controlling circadian rhythms;a similar clinical presentation of trigeminal pain, and autonomic activation. 2. There is much overlap in the diagnostic features of individual TACs. 3. In contrast, treatment response is relatively specific and aids in establishing a definitive diagnosis. 4. TACs are often presentations of underlying pathology; all patients should be imaged. 5. The aim of the article is to provide the reader with a broad introduction to, and an overview of, TACs. The reading list is extensive for the interested reader. PMID:26516482
Olfactory threshold increase in trigeminal neuralgia after balloon compression.
Siqueira, S R D T; Nóbrega, J C M; Teixeira, M J; Siqueira, J T T
2006-12-01
Idiopathic trigeminal neuralgia (ITN) is a well-known disease often treated with neurosurgical procedures, which may produce sensorial abnormalities, such as numbness, dysesthesia and taste complaints. We studied 12 patients that underwent this technique, in order to verify pain, gustative and olfactory thresholds abnormalities, with a follow-up of 120 days. We compared the patients with a matched control group of 12 patients. Our results found a significant difference in the olfactory threshold at the immediate post-operative period (p=0.048). We concluded that injured trigeminal fibers are probably associated with the increase in the olfactory threshold after the surgery, supporting the sensorial interaction theory.
Blast Fragmentation Modeling and Analysis
2010-10-31
weapons device containing a multiphase blast explosive (MBX). 1. INTRODUCTION The ARL Survivability Lethality and Analysis Directorate (SLAD) is...velocity. In order to simulate the highly complex phenomenon, the exploding cylinder is modeled with the hydrodynamics code ALE3D , an arbitrary...Lagrangian-Eulerian multiphysics code, developed at Lawrence Livermore National Laboratory. ALE3D includes physical properties, constitutive models for
Huang, Jie; Ni, Zhongge; Finch, Philip
2017-09-01
Varicella zoster virus reactivation can cause permanent histological changes in the central and peripheral nervous system. Neural inflammatory changes or damage to the dorsal root ganglia sensory nerve fibers during reactivation can lead to postherpetic neuralgia (PHN). For PHN of the first division of the fifth cranial nerve (ophthalmic division of the trigeminal ganglion), there is evidence of inflammatory change in the ganglion and adjacent ocular neural structures. First division trigeminal nerve PHN can prove to be difficult and sometimes even impossible to manage despite the use of a wide range of conservative measures, including anticonvulsant and antidepressant medication. Steroids have been shown to play an important role by suppressing neural inflammatory processes. We therefore chose the trigeminal ganglion as an interventional target for an 88-year-old woman with severe ophthalmic division PHN after she failed to respond to conservative treatment. Under fluoroscopic guidance, a trigeminal ganglion nerve block was performed with lidocaine combined with dexamethasone. A retrobulbar block with lidocaine and triamcinolone settled residual oculodynia. At 1-year follow-up, the patient remained pain free and did not require analgesic medication. To our knowledge, this is the first reported case of ophthalmic division PHN successfully treated with a combination of trigeminal ganglion and retrobulbar nerve block using a local anesthetic agent and steroid for central and peripheral neural inflammatory processes. © 2016 World Institute of Pain.
Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro.
Gulbransen, Brian D; Clapp, Tod R; Finger, Thomas E; Kinnamon, Sue C
2008-06-01
Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear. Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein alpha-gustducin, PLCbeta2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants. SCCs from the anterior nasal cavity were isolated from transgenic mice in which green fluorescent protein (GFP) expression was driven by either TRPM5 or gustducin. Isolated cells were exposed to a variety of test stimuli to determine which substances caused an increase in intracellular Ca2+ ([Ca2+]i). GFP-positive cells respond with increased [Ca2+]i to the bitter receptor ligand denatonium and this response is blocked by the PLC inhibitor U73122. In addition, GFP+ cells respond to the neuromodulators adenosine 5'-triphosphate and acetylcholine but only very rarely to other bitter-tasting or trigeminal stimuli. Our results demonstrate that TRPM5- and gustducin-expressing nasal SCCs respond to the T2R agonist denatonium via a PLC-coupled transduction cascade typical of T2Rs in the taste system.
Greco, M C; Capuano, A; Navarra, P; Tringali, G
2016-07-01
Several classes of drugs are effective in prevention and treatment of migraine, although they may differ among each other in their mode of action and in indications. One such class is represented by antiepileptics. Lacosamide is an approved antiepileptic drug that also shows antinociceptive activity in animal models, including analgesic efficacy in central and trigeminal pain. Calcitonin gene-related peptide (CGRP) is considered the main neuro-mediator of trigeminal signalling, playing an essential role in headache, migraine in particular. Here, we investigated the effects of lacosamide on CGRP signalling in both in vitro and ex vivo/vitro models in the rat. We assessed: (1) CGRP released from brainstem explants at baseline or after pharmacological challenges; and (2) CGRP levels in brain areas after in vivo treatments with test drugs. We found that: (1) lacosamide inhibits CGRP release from brainstem explants under basal conditions as well as after stimulation by 56 mM KCl, 10 μM veratridine or 1 μM capsaicin; and (2) the i.p. administration of nitroglycerine produces an increase in CGRP levels in the brainstem and trigeminal ganglia, which is inhibited by a pre-treatment with lacosamide. These findings provide preliminary evidence suggesting that lacosamide is able to control pain transmission under conditions affecting the trigeminal system, such as migraine. © 2015 European Pain Federation - EFIC®
Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo
2016-02-01
To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.
Cady, Ryan J.; Denson, Jennifer E.; Durham, Paul L.
2013-01-01
Scope Central sensitization is implicated in the pathology of temporomandibular joint disorder (TMD) and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves. Methods and results Male Sprague Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 14 days prior to bilateral injection of complete Freund’s adjuvant (CFA) into the temporomandibular joint to promote prolonged activation of trigeminal ganglion neurons and glia. While dietary cocoa stimulated basal expression of GLAST and MKP-1 when compared to animals on a normal diet, cocoa suppressed basal calcitonin gene-related peptide levels in the STN. CFA-stimulated levels of protein kinase A, P2X3, P-p38, GFAP, and OX-42, whose elevated levels in the STN are implicated in central sensitization, were repressed to near control levels in animals on a cocoa enriched diet. Similarly, dietary cocoa repressed CFA-stimulated inflammatory cytokine expression. Conclusion Based on our findings, we speculate that cocoa enriched diets could be beneficial as a natural therapeutic option for TMD and other chronic orofacial pain conditions. PMID:23576361
Robo2 determines subtype-specific axonal projections of trigeminal sensory neurons
Pan, Y. Albert; Choy, Margaret; Prober, David A.; Schier, Alexander F.
2012-01-01
How neurons connect to form functional circuits is central to the understanding of the development and function of the nervous system. In the somatosensory system, perception of sensory stimuli to the head requires specific connections between trigeminal sensory neurons and their many target areas in the central nervous system. Different trigeminal subtypes have specialized functions and downstream circuits, but it has remained unclear how subtype-specific axonal projection patterns are formed. Using zebrafish as a model system, we followed the development of two trigeminal sensory neuron subtypes: one that expresses trpa1b, a nociceptive channel important for sensing environmental chemicals; and a distinct subtype labeled by an islet1 reporter (Isl1SS). We found that Trpa1b and Isl1SS neurons have overall similar axon trajectories but different branching morphologies and distributions of presynaptic sites. Compared with Trpa1b neurons, Isl1SS neurons display reduced branch growth and synaptogenesis at the hindbrain-spinal cord junction. The subtype-specific morphogenesis of Isl1SS neurons depends on the guidance receptor Robo2. robo2 is preferentially expressed in the Isl1SS subset and inhibits branch growth and synaptogenesis. In the absence of Robo2, Isl1SS afferents acquire many of the characteristics of Trpa1b afferents. These results reveal that subtype-specific activity of Robo2 regulates subcircuit morphogenesis in the trigeminal sensory system. PMID:22190641
Astringency: A More Stringent Definition
Gong, Naihua N.; Matsunami, Hiroaki
2014-01-01
Despite being an everyday sensory experience, the nature of astringency perception is not clear. In this issue of Chemical Senses, Schöbel et al. demonstrate that astringency is a trigeminal sensation in human, and astringents trigger a G protein-coupled pathway in trigeminal ganglion cells in the mouse. PMID:24860069
ERIC Educational Resources Information Center
Lee, Jeongwoo
2017-01-01
The objectives of this dissertation include describing and analyzing the patterns of inequality in ALE participation at both the micro and macro levels. Special attention is paid to social origins of individual adults and their association with two groups of macro-level factors, social inequality (income, education, and skill inequality) and…
Ecological perspectives of land use history: The Arid Lands Ecology (ALE) Reserve
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hinds, N R; Rogers, L E
The objective of this study was to gather information on the land use history of the Arid Land Ecology (ALE) Reserve so that current ecological research could be placed within a historical perspective. The data were gathered in the early 1980s by interviewing former users of the land and from previously published research (where available). Interviews with former land users of the ALE Reserve in Benton County, Washington, revealed that major land uses from 1880 to 1940 were homesteading, grazing, oil/gas production, and road building. Land use practices associated with grazing and homesteading have left the greatest impact on themore » landscape. Disturbed sites where succession is characterized by non-native species, plots where sagebrush was railed away, and sheep trails are major indications today of past land uses. Recent estimates of annual bunchgrass production do ALE do not support the widespread belief that bunchgrass were more productive during the homesteading era, though the invasion of cheatgrass (Bromus tectorum), Jim Hill mustard (Sisymbrium altissium), and other European alien plant species has altered pre-settlement succession patterns. 15 refs., 6 figs., 1 tab.« less
Renton, T
2017-07-01
The issues specific to trigeminal pain include the complexity of the region, the problematic impact on daily function and significant psychological impact (J Dent, 43, 2015, 1203). By nature of the geography of the pain (affecting the face, eyes, scalp, nose, mouth), it may interfere with just about every social function we take for granted and enjoy (J Orofac Pain, 25, 2011, 333). The trigeminal nerve is the largest sensory nerve in the body, protecting the essential organs that underpin our very existence (brain, eyes, nose, mouth). It is no wonder that pain within the trigeminal system in the face is often overwhelming and inescapable for the affected individual. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Application of cyclic fluorocarbon/argon discharges to device patterning
DOE Office of Scientific and Technical Information (OSTI.GOV)
Metzler, Dominik, E-mail: dmetzler@umd.edu; Uppireddi, Kishore; Bruce, Robert L.
2016-01-15
With increasing demands on device patterning to achieve smaller critical dimensions and pitches for the 5 nm node and beyond, the need for atomic layer etching (ALE) is steadily increasing. In this work, a cyclic fluorocarbon/Ar plasma is successfully used for ALE patterning in a manufacturing scale reactor. Self-limited etching of silicon oxide is observed. The impact of various process parameters on the etch performance is established. The substrate temperature has been shown to play an especially significant role, with lower temperatures leading to higher selectivity and lower etch rates, but worse pattern fidelity. The cyclic ALE approach established with thismore » work is shown to have great potential for small scale device patterning, showing self-limited etching, improved uniformity and resist mask performance.« less
Application of cyclic fluorocarbon/argon discharges to device patterning
Metzler, Dominik; Uppiredi, Kishore; Bruce, Robert L.; ...
2015-11-13
With increasing demands on device patterning to achieve smaller critical dimensions and pitches for the 5nm node and beyond, the need for atomic layer etching (ALE) is steadily increasing. In this study, a cyclic fluorocarbon/Ar plasma is successfully used for ALE patterning in a manufacturing scale reactor. Self-limited etching of silicon oxide is observed. The impact of various process parameters on the etch performance is established. The substrate temperature has been shown to play an especially significant role, with lower temperatures leading to higher selectivity and lower etch rates, but worse pattern fidelity. The cyclic ALE approach established with thismore » work is shown to have great potential for small scale device patterning, showing self-limited etching, improved uniformity and resist mask performance.« less
Ringkamp, Matthias; Wooten, Matthew; Carson, Benjamin S; Lim, Michael; Hartke, Timothy; Guarnieri, Michael
2016-02-01
Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model. This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion. Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement. Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans.
Trigeminal activation using chemical, electrical, and mechanical stimuli.
Iannilli, E; Del Gratta, C; Gerber, J C; Romani, G L; Hummel, T
2008-10-15
Tactile, proprioceptive, and nociceptive information, including also chemosensory functions are expressed in the trigeminal nerve sensory response. To study differences in the processing of different stimulus qualities, we performed a study based on functional magnetic resonance imaging. The first trigeminal branch (ophthalmic nerve) was activated by (a) intranasal chemical stimulation with gaseous CO2 which produces stinging and burning sensations, but is virtually odorless, (b) painful, but not nociceptive specific cutaneous electrical stimulation, and (c) cutaneous mechanical stimulation using air puffs. Eighteen healthy subjects participated (eight men, 10 women, mean age 31 years). Painful stimuli produced patterns of activation similar to what has been reported for other noxious stimuli, namely activation in the primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and thalamus. In addition, analyses indicated intensity-related activation in the prefrontal cortex which was specifically involved in the evaluation of stimulus intensity. Importantly, the results also indicated similarities between activation patterns after intranasal chemosensory trigeminal stimulation and patterns usually found following intranasal odorous stimulation, indicating the intimate connection between these two systems in the processing of sensory information.
Bhatjiwale, M; Bhatjiwale, M; Naik, L D; Chopade, P
2018-05-29
Trigeminal neuralgia and deafferentation neuropathic pain, or trigeminal neuropathy, are different symptomatologies, rarely reported to present together. The case of a 65-year-old gentleman suffering from trigeminal neuralgia of the maxillary and mandibular division is reported. He first underwent an infraorbital neurectomy that was complicated by deafferentation neuropathic pain, whilst his mandibular neuralgia continued. He was treated successfully for both the neuropathic and neuralgic symptoms in the same session using ultra-extended euthermic pulsed radiofrequency treatment for the maxillary division (V2) and radiofrequency thermocoagulation for the mandibular division (V3). This report is novel in describing the use of dual modalities in the same session for two distinct coexisting clinical entities in two different divisions of the same cranial nerve. The use of ultra-extended pulsed radiofrequency treatment for neuropathic pain in this case is also unique. Nearly 2years after the procedure, the patient continues to have complete pain relief. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Hernández, C J; Ortíz, T; Rosa, C; Foster, K; Tyagi, M; Lugo, N; Albrecht, R; Chinapen, S
2007-04-01
Mucociliary activity is an important clearance mechanism in the respiratory system of air breathing vertebrates. Substance P (SP) and acetylcholine play a key role in the stimulation of the mucociliary transport in the frog palate. In this study, retrograde neuronal tracing was combined with immunocytochemistry for SP and choline acetyl transferase (ChAT) in the trigeminal ganglion and for neurokinin-1 receptor (NK1R) in the palate of Rana pipiens. The cells of origin of the palatine nerve were identified in the trigeminal ganglion using the retrograde tracer Fluorogold (FG). Optimal labeling of FG cells in the trigeminal ganglion was obtained at 96 h of exposure. Immunoflorescent shows that SP and acetylcholine are co-localized in 92% of the cells labeled with FG in the trigeminal ganglion. NK1 receptors were found in the membrane of epithelial and goblet cells of the palate. Ultrastructural study of the palate showed axonal-like endings with vesicles in connection with epithelial and goblet cells. These results further support the concerted action of both neurotransmitters in the regulation of mucociliary activity in the frog palate.
Rehabilitation of the trigeminal nerve
Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank
2005-01-01
When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts. In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID:22073060
Role of transcutaneous electric nerve stimulation in the management of trigeminal neuralgia.
Singla, Sanju; Prabhakar, Vikram; Singla, Rajan Kumar
2011-07-01
Trigeminal neuralgia typically involves nerves supplying teeth, jaws and face of older females. Though the etiology is usually obscure, different treatment modalities have been tried for it viz. medicinal treatment, injection alcohol, peripheral neurectomy, rhizotomy, and microvascular decompression etc. Transcutaneous electric nerve stimulation (TENS) is an emerging and promising option for management of such patients. The present study was designed with an aim to study the efficacy of TENS in management of trigeminal neuralgia. The study was conducted on 30 patients of trigeminal neuralgia confirmed by diagnostic nerve block. They were given bursts of TENS for 20-40 days over the path of the affected nerve and subsequently evaluated at 1 month and 3 month intervals by visual analogue scale (VAS), verbal pain scale (VPS), a functional outcome scales for main daily activities like sleep, chewing, talking, or washing face. The results showed that, on VAS, the score decreased from 8.9 (Pre TENS) to 3.1 at 1 month and 1.3 at 3 months, and on VPS, the score decreased from 3.5 (Pre TENS) to 1.2 at 1 month and 0.3 at 3 months. Similarly, a considerable decrease in scores was seen on functional outcome scale for different activities. No side effects like irritation or redness of skin were seen in any of the patients. Thus, TENS was found to be a safe, easily acceptable, and non-invasive outdoor patient department procedure for management of trigeminal neuralgia.
Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E
2014-01-01
Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher-order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42°C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772
Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro
Gulbransen, Brian D; Clapp, Tod R; Kinnamon, Sue C; Finger, Thomas E
2009-01-01
Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear (Finger et al. 2003). Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein α-gustducin, PLCβ2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants. SCCs from the anterior nasal cavity were isolated from transgenic mice in which green fluorescent protein (GFP) expression was driven by either TRPM5 or gustducin. Isolated cells were exposed to a variety of test stimuli to determine which substances caused an increase in intracellular Ca2+ ([Ca2+]i). GFP positive cells respond with increased [Ca2+]i to the bitter receptor ligand denatonium, and this response is blocked by the PLC inhibitor U73122. In addition GFP+ cells respond to the PLC activator 3M3FBS, the neuromodulators ATP and ACh, but only very rarely to other bitter-tasting or trigeminal stimuli. Our results demonstrate that TRPM5- and gustducin-expressing nasal SCCs respond to the T2R agonist, denatonium via a PLC-coupled transduction cascade typical of T2Rs in the taste system. PMID:18417634
Mehboob, Riffat
2017-01-01
Sudden demise of a healthy fetus or a neonate is a very tragic episode in the life of parents. These deaths have been a mystery since ages but still remain unexplained. This review proposes the involvement of trigeminal nerve, neurotransmitter substance P (SP), and its receptor neurokinin 1 (NK-1R) in regulation of cardiorespiratory control in fetuses and newborns. Anomalies and immaturity of neuroregulatory systems such as trigeminal system in medulla oblongata of brainstem may provide a possible mechanism of sudden perinatal deaths. Vulnerable infants are born with respiratory center immaturity which in combination with any stressor such as cold, hypoxia, and smoking may lead to cessation of breathing and ventilatory response. SP/NK-1R may be involved in regulating the ventilatory control in neonates while it is decreased in fetal and adult life in humans, and any alterations from these may lead to irreversible sleep apnea and fatal breathing, ultimately sudden death. This review summarizes the studies performed to highlight the expression of SP or NK-1R in sudden perinatal deaths and proposes the involvement of trigeminal ganglion along with its nerve and SP/NK-1R expression alteration as one of the possible pathophysiological underlying mechanism. However, further studies are required to explore the role of SP, NK-1R, and trigeminal system in the pathogenesis of sudden infant deaths, sudden intrauterine deaths, stillbirths, and sudden deaths later in human life. PMID:28348544
Mehboob, Riffat
2017-01-01
Sudden demise of a healthy fetus or a neonate is a very tragic episode in the life of parents. These deaths have been a mystery since ages but still remain unexplained. This review proposes the involvement of trigeminal nerve, neurotransmitter substance P (SP), and its receptor neurokinin 1 (NK-1R) in regulation of cardiorespiratory control in fetuses and newborns. Anomalies and immaturity of neuroregulatory systems such as trigeminal system in medulla oblongata of brainstem may provide a possible mechanism of sudden perinatal deaths. Vulnerable infants are born with respiratory center immaturity which in combination with any stressor such as cold, hypoxia, and smoking may lead to cessation of breathing and ventilatory response. SP/NK-1R may be involved in regulating the ventilatory control in neonates while it is decreased in fetal and adult life in humans, and any alterations from these may lead to irreversible sleep apnea and fatal breathing, ultimately sudden death. This review summarizes the studies performed to highlight the expression of SP or NK-1R in sudden perinatal deaths and proposes the involvement of trigeminal ganglion along with its nerve and SP/NK-1R expression alteration as one of the possible pathophysiological underlying mechanism. However, further studies are required to explore the role of SP, NK-1R, and trigeminal system in the pathogenesis of sudden infant deaths, sudden intrauterine deaths, stillbirths, and sudden deaths later in human life.
Hyper-excitability of brainstem pathways in cerebral palsy.
Smith, Allison Teresa; Gorassini, Monica Ann
2018-06-27
Individuals with cerebral palsy (CP) experience impairments in the control of head and neck movements, suggesting dysfunction in brainstem circuitry. To examine if brainstem circuitry is altered in CP we compared reflexes evoked in the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults with CP and age/sex-matched controls. Increasing the intensity of trigeminal nerve stimulation produced progressive increases in the long-latency suppression of ongoing SCM EMG in controls. In contrast, participants with CP showed progressively increased facilitation around the same reflex window, suggesting heightened excitability of brainstem pathways. We also examined if there was altered activation of cortico-brainstem pathways in response to pre-natal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were conditioned by a prior trigeminal afferent stimulation were more facilitated in CP compared to controls, especially in ipsilateral MEPs that are likely mediated by cortico-reticulospinal pathways. In some participants with CP, but not in controls, a combined trigeminal nerve and cortical stimulation near threshold intensities produced large, long-lasting responses in both the SCM and biceps brachii muscles. We propose that the enhanced excitatory responses evoked from trigeminal and cortical inputs in CP are produced by heightened excitability of brainstem circuits, resulting in the augmented activation of reticulospinal pathways. Enhanced activation of reticulospinal pathways in response to early injury of the corticospinal tract may provide a compensated activation of the spinal cord, or alternatively, contribute to impairments in the precise control of head and neck functions.
Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia
Vit, Jean-Philippe; Ohara, Peter T; Sundberg, Christopher; Rubi, Blanca; Maechler, Pierre; Liu, Chunyan; Puntel, Mariana; Lowenstein, Pedro; Castro, Maria; Jasmin, Luc
2009-01-01
Background Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animal model of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) gene into satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector with high tropisms for glial cells. We postulated that GABA produced from the expression of GAD would reduce pain behavior by acting on GABA receptors on neurons within the ganglion. Results Injection of adenoviral vectors (AdGAD65) directly into the trigeminal ganglion leads to sustained expression of the GAD65 isoform over the 4 weeks observation period. Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABA synthesis were mainly in SGCs. GABAA and GABAB receptors were both seen in sensory neurons, yet only GABAA receptors decorated the neuronal surface. GABA receptors were not found on SGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statistically significant decrease of pain behavior in the orofacial formalin test, a model of inflammatory pain. Rats injected with control virus (AdGFP or AdLacZ) had no reduction in their pain behavior. AdGAD65-dependent analgesia was blocked by bicuculline, a selective GABAA receptor antagonist, but not by CGP46381, a selective GABAB receptor antagonist. Conclusion Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks pain behavior by acting on GABAA receptors on neuronal perikarya. PMID:19656360
Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia.
Vit, Jean-Philippe; Ohara, Peter T; Sundberg, Christopher; Rubi, Blanca; Maechler, Pierre; Liu, Chunyan; Puntel, Mariana; Lowenstein, Pedro; Castro, Maria; Jasmin, Luc
2009-08-05
Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animal model of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) gene into satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector with high tropisms for glial cells. We postulated that GABA produced from the expression of GAD would reduce pain behavior by acting on GABA receptors on neurons within the ganglion. Injection of adenoviral vectors (AdGAD65) directly into the trigeminal ganglion leads to sustained expression of the GAD65 isoform over the 4 weeks observation period. Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABA synthesis were mainly in SGCs. GABAA and GABAB receptors were both seen in sensory neurons, yet only GABAA receptors decorated the neuronal surface. GABA receptors were not found on SGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statistically significant decrease of pain behavior in the orofacial formalin test, a model of inflammatory pain. Rats injected with control virus (AdGFP or AdLacZ) had no reduction in their pain behavior. AdGAD65-dependent analgesia was blocked by bicuculline, a selective GABAA receptor antagonist, but not by CGP46381, a selective GABAB receptor antagonist. Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks pain behavior by acting on GABAA receptors on neuronal perikarya.
Transcriptome analysis of trigeminal ganglia following masseter muscle inflammation in rats
Park, Jennifer; Asgar, Jamila; Ro, Jin Y.
2016-01-01
Background Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined. In the present study, we performed RNA sequencing assay in rat trigeminal ganglia to identify transcriptome profiles of genes relevant to hyperalgesia following inflammation of the rat masseter muscle. Results Masseter inflammation differentially regulated >3500 genes in trigeminal ganglia. Predominant biological pathways were predicted to be related with activation of resident non-neuronal cells within trigeminal ganglia or recruitment of immune cells. To focus our analysis on the genes more relevant to nociceptors, we selected genes implicated in pain mechanisms, genes enriched in small- to medium-sized sensory neurons, and genes enriched in TRPV1-lineage nociceptors. Among the 2320 candidate genes, 622 genes showed differential expression following masseter inflammation. When the analysis was limited to these candidate genes, pathways related with G protein-coupled signaling and synaptic plasticity were predicted to be enriched. Inspection of individual gene expression changes confirmed the transcriptional changes of multiple nociceptor genes associated with masseter hyperalgesia (e.g., Trpv1, Trpa1, P2rx3, Tac1, and Bdnf) and also suggested a number of novel probable contributors (e.g., Piezo2, Tmem100, and Hdac9). Conclusion These findings should further advance our understanding of peripheral mechanisms involved in persistent craniofacial muscle pain conditions and provide a rational basis for identifying novel genes or sets of genes that can be potentially targeted for treating such conditions. PMID:27702909
He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen
2014-11-15
The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that tooth extraction should be avoided in these populations.
Clinical value of a self-designed training model for pinpointing and puncturing trigeminal ganglion.
He, Yu-Quan; He, Shu; Shen, Yun-Xia; Qian, Cheng
2014-04-01
OBJECTIVES. A training model was designed for learners and young physicians to polish their skills in clinical practices of pinpointing and puncturing trigeminal ganglion. METHODS. A head model, on both cheeks of which the deep soft tissue was replaced by stuffed organosilicone and sponge while the superficial soft tissue, skin and the trigeminal ganglion were made of organic silicon rubber for an appearance of real human being, was made from a dried skull specimen and epoxy resin. Two physicians who had experiences in puncturing foramen ovale and trigeminal ganglion were selected to test the model, mainly for its appearance, X-ray permeability, handling of the puncture, and closure of the puncture sites. Four inexperienced physicians were selected afterwards to be trained combining Hartel's anterior facial approach with the new method of real-time observation on foramen ovale studied by us. RESULTS. Both appearance and texture of the model were extremely close to those of a real human. The fact that the skin, superficial soft tissue, deep muscles of the cheeks, and the trigeminal ganglion made of organic silicon rubber all had great elasticity resulted in quick closure and sealing of the puncture sites. The head model made of epoxy resin had similar X-ray permeability to a human skull specimen under fluoroscopy. The soft tissue was made of radiolucent material so that the training can be conducted with X-ray guidance. After repeated training, all the four young physicians were able to smoothly and successfully accomplish the puncture. CONCLUSION. This self-made model can substitute for cadaver specimen in training learners and young physicians on foramen ovale and trigeminal ganglion puncture. It is very helpful for fast learning and mastering this interventional operation skill, and the puncture accuracy can be improved significantly with our new method of real-time observation on foramen ovale.
Nagoya, Kouta; Nakamura, Shiro; Ikeda, Keiko; Onimaru, Hiroshi; Yoshida, Atsushi; Nakayama, Kiyomi; Mochizuki, Ayako; Kiyomoto, Masaaki; Sato, Fumihiko; Kawakami, Kiyoshi; Takahashi, Koji; Inoue, Tomio
2017-09-01
Phox2b encodes a paired-like homeodomain-containing transcription factor essential for development of the autonomic nervous system. Phox2b-expressing (Phox2b + ) neurons are present in the reticular formation dorsal to the trigeminal motor nucleus (RdV) as well as the nucleus of the solitary tract and parafacial respiratory group. However, the nature of Phox2b + RdV neurons is still unclear. We investigated the physiological and morphological properties of Phox2b + RdV neurons using postnatal day 2-7 transgenic rats expressing yellow fluorescent protein under the control of Phox2b. Almost all of Phox2b + RdV neurons were glutamatergic, whereas Phox2b-negative (Phox2b - ) RdV neurons consisted of a few glutamatergic, many GABAergic, and many glycinergic neurons. The majority (48/56) of Phox2b + neurons showed low-frequency firing (LF), while most of Phox2b - neurons (35/42) exhibited high-frequency firing (HF) in response to intracellularly injected currents. All, but one, Phox2b + neurons (55/56) did not fire spontaneously, whereas three-fourths of the Phox2b - neurons (31/42) were spontaneously active. K + channel and persistent Na + current blockers affected the firing of LF and HF neurons. The majority of Phox2b + (35/46) and half of the Phox2b - neurons (19/40) did not respond to stimulations of the mesencephalic trigeminal nucleus, the trigeminal tract, and the principal sensory trigeminal nucleus. Biocytin labeling revealed that about half of the Phox2b + (5/12) and Phox2b - RdV neurons (5/10) send their axons to the trigeminal motor nucleus. These results suggest that Phox2b + RdV neurons have distinct neurotransmitter phenotypes and firing properties from Phox2b - RdV neurons and might play important roles in feeding-related functions including suckling and possibly mastication. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Long-Term Results for Trigeminal Schwannomas Treated With Gamma Knife Surgery
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hasegawa, Toshinori, E-mail: h-toshi@komakihp.gr.jp; Kato, Takenori; Iizuka, Hiroshi
Purpose: Surgical resection is considered the desirable curative treatment for trigeminal schwannomas. However, complete resection without any complications remains challenging. During the last several decades, stereotactic radiosurgery (SRS) has emerged as a minimally invasive treatment modality. Information regarding long-term outcomes of SRS for patients harboring trigeminal schwannomas is limited because of the rarity of this tumor. The aim of this study was to evaluate long-term tumor control and functional outcomes in patients harboring trigeminal schwannomas treated with SRS, specifically with gamma knife surgery (GKS). Methods and Materials: Fifty-three patients harboring trigeminal schwannomas treated with GKS were evaluated. Of these, 2more » patients (4%) had partial irradiation of the tumor, and 34 patients (64%) underwent GKS as the initial treatment. The median tumor volume was 6.0 cm{sup 3}. The median maximum and marginal doses were 28 Gy and 14 Gy, respectively. Results: The median follow-up period was 98 months. On the last follow-up image, 7 patients (13%) had tumor enlargement, including the 2 patients who had partial treatment. Excluding the 2 patients who had partial treatment, the actuarial 5- and 10-year progression-free survival (PFS) rates were 90% and 82%, respectively. Patients with tumors compressing the brainstem with deviation of the fourth ventricle had significantly lower PFS rates. If those patients with tumors compressing the brainstem with deviation of the fourth ventricle are excluded, the actuarial 5- and 10-year PFS rates increased to 95% and 90%, respectively. Ten percent of patients had worsened facial numbness or pain in spite of no tumor progression, indicating adverse radiation effect. Conclusions: GKS can be an acceptable alternative to surgical resection in patients with trigeminal schwannomas. However, large tumors that compress the brainstem with deviation of the fourth ventricle should be surgically removed first and then treated with GKS when necessary.« less
Jääskeläinen, Satu K
2004-01-01
Chronic orofacial pain represents a diagnostic and treatment challenge for the clinician. Some conditions, such as atypical facial pain, still lack proper diagnostic criteria, and their etiology is not known. The recent development of neurophysiological methods and quantitative sensory testing for the examination of the trigeminal somatosensory system offers several tools for diagnostic and etiological investigation of orofacial pain. This review presents some of these techniques and the results of their application in studies on orofacial pain and sensory dysfunction. Clinical neurophysiological investigation has greater diagnostic accuracy and sensitivity than clinical examination in the detection of the neurogenic abnormalities of either peripheral or central origin that may underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological testing may also reveal trigeminal pathology when magnetic resonance imaging has failed to detect it, so these methods should be considered complementary to each other in the investigation of orofacial pain patients. The blink reflex, corneal reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the recording of trigeminal somatosensory-evoked potentials with near-nerve stimulation have all proved to be sensitive and reliable in the detection of dysfunction of the myelinated sensory fibers of the trigeminal nerve or its central connections within the brainstem. With appropriately small thermodes, thermal quantitative sensory testing is useful for the detection of trigeminal small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most sensitive to lesions causing axonal injury. By combining different techniques for investigation of the trigeminal system, an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. Neurophysiological and quantitative sensory tests have already highlighted some similarities among various orofacial pain conditions and have shown heterogeneity within clinical diagnostic categories. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.
Cryptanalysis of the Sodark Family of Cipher Algorithms
2017-09-01
software project for building three-bit LUT circuit representations of S- boxes is available as a GitHub repository [40]. It contains several improvements...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release. Distribution is unlimited. 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) The...second- and third-generation automatic link establishment (ALE) systems for high frequency radios. Radios utilizing ALE technology are in use by a
Two Mechanisms Involved in Trigeminal CGRP Release: Implications for Migraine Treatment
Durham, Paul L.; Masterson, Caleb G.
2012-01-01
Objective The goal of this study was to better understand the cellular mechanisms involved in proton stimulation of calcitonin gene-related peptide (CGRP) secretion from cultured trigeminal neurons by investigating the effects of two anti-migraine therapies, onabotulinumtoxin A and rizatriptan. Background Stimulated CGRP release from peripheral and central terminating processes of trigeminal ganglia neurons is implicated in migraine pathology by promoting inflammation and nociception. Based on models of migraine pathology, several inflammatory molecules including protons are thought to facilitate sensitization and activation of trigeminal nociceptive neurons and stimulate CGRP secretion. Despite the reported efficacy of triptans and onabotulinumtoxinA to treat acute and chronic migraine, respectively, a substantial number of migraneurs do not get adequate relief with these therapies. A possible explanation is that triptans and onabutulinumtoxinA are not able to block proton mediated CGRP secretion. Methods CGRP secretion from cultured primary trigeminal ganglia neurons was quantitated by radioimmunoassay while intracellular calcium and sodium levels were measured in neurons via live cell imaging using Fura2-AM and SBFI-AM, respectively. The expression of ASIC3 was determined by immunocytochemistry and western blot analysis. In addition, the involvement of ASICs in mediating proton stimulation of CGRP was investigated using the potent and selective ASIC3 inhibitor APETx2. Results While KCl caused a significant increase in CGRP secretion that was significantly repressed by treatment with EGTA, onabotulinumtoxinA, and rizatriptan, the stimulatory effect of protons (pH 5.5) was not suppressed by EGTA, onabotulinumtoxinA, or rizatriptan. In addition, while KCl caused a transient increase in intracellular calcium levels that was blocked by EGTA, no appreciable change in calcium levels was observed with proton treatment. However, protons did significantly increase the intracellular level of sodium ions. Under our culture conditions, ASIC3 was shown to be expressed in most trigeminal ganglion neurons. Importantly, proton stimulation of CGRP secretion was repressed by pretreatment with the ASIC3 inhibitor APETx2, but not the TRPV1 antagonist capsazepine. Conclusions Our findings provide evidence that proton regulated release of CGRP from trigeminal neurons utilizes a different mechanism than the calcium and SNAP-25 dependent pathways that are inhibited by the anti-migraine therapies rizatriptan and onabotulinumtoxinA. PMID:23095108
LaCroix, Ryan A; Sandberg, Troy E; O'Brien, Edward J; Utrilla, Jose; Ebrahim, Ali; Guzman, Gabriela I; Szubin, Richard; Palsson, Bernhard O; Feist, Adam M
2015-01-01
Adaptive laboratory evolution (ALE) has emerged as an effective tool for scientific discovery and addressing biotechnological needs. Much of ALE's utility is derived from reproducibly obtained fitness increases. Identifying causal genetic changes and their combinatorial effects is challenging and time-consuming. Understanding how these genetic changes enable increased fitness can be difficult. A series of approaches that address these challenges was developed and demonstrated using Escherichia coli K-12 MG1655 on glucose minimal media at 37°C. By keeping E. coli in constant substrate excess and exponential growth, fitness increases up to 1.6-fold were obtained compared to the wild type. These increases are comparable to previously reported maximum growth rates in similar conditions but were obtained over a shorter time frame. Across the eight replicate ALE experiments performed, causal mutations were identified using three approaches: identifying mutations in the same gene/region across replicate experiments, sequencing strains before and after computationally determined fitness jumps, and allelic replacement coupled with targeted ALE of reconstructed strains. Three genetic regions were most often mutated: the global transcription gene rpoB, an 82-bp deletion between the metabolic pyrE gene and rph, and an IS element between the DNA structural gene hns and tdk. Model-derived classification of gene expression revealed a number of processes important for increased growth that were missed using a gene classification system alone. The methods described here represent a powerful combination of technologies to increase the speed and efficiency of ALE studies. The identified mutations can be examined as genetic parts for increasing growth rate in a desired strain and for understanding rapid growth phenotypes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
LaCroix, Ryan A.; Sandberg, Troy E.; O'Brien, Edward J.; Utrilla, Jose; Ebrahim, Ali; Guzman, Gabriela I.; Szubin, Richard; Palsson, Bernhard O.
2014-01-01
Adaptive laboratory evolution (ALE) has emerged as an effective tool for scientific discovery and addressing biotechnological needs. Much of ALE's utility is derived from reproducibly obtained fitness increases. Identifying causal genetic changes and their combinatorial effects is challenging and time-consuming. Understanding how these genetic changes enable increased fitness can be difficult. A series of approaches that address these challenges was developed and demonstrated using Escherichia coli K-12 MG1655 on glucose minimal media at 37°C. By keeping E. coli in constant substrate excess and exponential growth, fitness increases up to 1.6-fold were obtained compared to the wild type. These increases are comparable to previously reported maximum growth rates in similar conditions but were obtained over a shorter time frame. Across the eight replicate ALE experiments performed, causal mutations were identified using three approaches: identifying mutations in the same gene/region across replicate experiments, sequencing strains before and after computationally determined fitness jumps, and allelic replacement coupled with targeted ALE of reconstructed strains. Three genetic regions were most often mutated: the global transcription gene rpoB, an 82-bp deletion between the metabolic pyrE gene and rph, and an IS element between the DNA structural gene hns and tdk. Model-derived classification of gene expression revealed a number of processes important for increased growth that were missed using a gene classification system alone. The methods described here represent a powerful combination of technologies to increase the speed and efficiency of ALE studies. The identified mutations can be examined as genetic parts for increasing growth rate in a desired strain and for understanding rapid growth phenotypes. PMID:25304508
NASA Astrophysics Data System (ADS)
Bonacci, Ognjen; Roje-Bonacci, Tanja
2010-05-01
Construction of grout curtains in karst terrains is primarily connected with dams and reservoirs. Their role is to increase watertightness and prevent progressive erosion. In this presentation hourly continuous measurement of groundwater level in two deep piezometers near the Đale reservoir is analysed. The Đale reservoir in the Cetina River began operation in 1989. The total length of the grout curtain is 3.9 km. It spreads 120 m bellow the Đale dam. First analysed piezometer A is drilled in the interior part of the system, between the reservoir and the grout curtain, while the second one B is located in its external part. Distance between them is 200 m. In natural conditions, prior the grout curtain construction, groundwater level fluctuation in both of them was similar (practically the same). Construction of the grout curtain extremely changed groundwater behaviour in each of them. During the six month of continuous monitoring, differences between groundwater levels in them range between +19.86 m (groundwater in B is lower than in A) and -12.77 m (groundwater in A is lower than in B). During the 77% of analysed period the groundwater level in interior piezometer A is higher than the groundwater level in external piezometer B. In other 23% of analysed period the groundwater level in outside piezometer B is higher than in inside A. The construction of the grout curtain caused unnaturally high hydrostatic gradients, which can accelerate the dissolutional expansion of karst fractures. As a result, unbearable leakage of the reservoir Đale can occur over its lifetime. Careful analyses of groundwater level behaviour discover some other very important characteristics of karst underground morphology.
Wu, Xin; Yang, Wenjing; Tong, Dandan; Sun, Jiangzhou; Chen, Qunlin; Wei, Dongtao; Zhang, Qinglin; Zhang, Meng; Qiu, Jiang
2015-07-01
In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimaging studies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex [such as the inferior parietal lobule (BA 40) and precuneus (BA 7)], anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex [such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)]. The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated concepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and forming distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability). © 2015 Wiley Periodicals, Inc.
Kämppi, Antti; Kämppi, Leena; Kemppainen, Pentti; Kanerva, Mari; Toppila, Jussi; Auranen, Mari
2018-05-01
Patients with unknown clinical or radiological asymmetry in the face structures combined with atrophy and weakness of the masticatory muscles should be comprehensively examined clinically and with MRI, neurophysiological measurements, and serologically. Malignant lesions or benign idiopathic unilateral trigeminal motor neuropathy should be considered as an etiological explanation for the asymmetry.
Chronic dysphagia and trigeminal anesthesia after trichloroethylene exposure
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lawrence, W.H.; Partyka, E.K.
1981-12-01
A patient is described who inhaled trichloroethylene fumes while working in a closed underground pit. At the time of exposure he developed dysphagia, dysarthria and dyspnea. Assessment of his condition 11 years after the incident indicated major damage of cranial nerves, particularly the trigeminal, chronic involvement of the bulbar cranial nerves, and resultant esophageal and pharnygeal motility impairment. (JMT)
Effects of Millimeter-Wave Electromagnetic Radiation on the Experimental Model of Migraine.
Sivachenko, I B; Medvedev, D S; Molodtsova, I D; Panteleev, S S; Sokolov, A Yu; Lyubashina, O A
2016-02-01
Effects of millimeter-wave electromagnetic radiation (40 GHz frequency, 0.01 mW power) on the spontaneous fi ring of convergent neurons of the spinal trigeminal nucleus and their responses to electrical stimulation of the dura mater were studied in neurophysiological experiments on rats. Irradiation of the area of cutaneous receptive fields of spinal trigeminal nucleus reversibly inhibited both spontaneous discharges and activity induced by electrical stimulation of the dura mater. The second and third exposures to electromagnetic radiation with an interval of 10 min were ineffective. These results suggest that suppression of neuronal excitability in the spinal trigeminal ganglion can be a mechanism of the anti-migraine effects of electromagnetic radiation observed in clinical practice.
Poon, C Y
2000-12-01
Trigeminal neuralgia is a unique neuropathic syndrome confined to the trigeminal system with no analog in the somatic dermatomes or the other cranial nerves. Medical treatment remains the first line of treatment with carbamezapine as the drug of choice. Surgery, central or peripheral is indicated when medical treatment fails or its side effects diminishes quality of life. No surgery offers a permanent cure. Recurrence rates are highest in the most peripheral techniques but these also have the lowest morbidity. Cryotherapy produces a reliable, prolonged and reversible nerve block with no aggravation of symptoms. It is a simple and repeatable procedure in patients who want to avoid major surgery or where it is contra-indicated.
Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge
Ang, Jensen W. J.; Khanna, Arjun; Walcott, Brian P.; Kahle, Kristopher T.; Eskandar, Emad N.
2015-01-01
We describe an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel’s cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intra-cranial tumors, but its incidence has been steadily increasing in some groups [1]. It usually arises in periventricular cerebral white matter, reports of lymphoma in extra-axial regions are rare [2]. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms. PMID:25865026
Severe psychosocial compromise in idiopathic trigeminal neuralgia: case report.
Siqueira, Silvia R D T; Teixeira, Manoel J; de Siqueira, José T T
2010-03-01
This article describes a 60-year-old man with 17 years of idiopathic trigeminal neuralgia (ITN) which affected tooth brushing for 6 years, causing severe dental complications and psychosocial problems. Case report. Following ITN diagnosis, this patient underwent neurosurgery (microcompression of the trigeminal ganglion with a balloon) with immediate relief, but after three months, pain recurred and was accompanied by dysesthesia and periodontal disease. After dental treatment, he had complete alleviation of pain and no further need of medication over the following 3 years. The intense suffering of this patient represents the importance of a multidisciplinary evaluation for pain-caused secondary complications. ITN is a simple diagnosis but may have complex course. Appropriately trained health professionals are necessary to evaluate and treat these patients.
Xiao, Hui; Jacobsen, Andre; Chen, Ziqian; Wang, Yang
2017-01-01
Traumatic brain injury (TBI) can result in significant social dysfunction, which is represented by impairment to social-cognitive abilities (i.e. social cognition, social attention/executive function and communication). This study is aimed to explore brain networks mediating the social dysfunction after TBI and its underlying mechanisms. We performed a quantitative meta-analysis using the activation likelihood estimation (ALE) approach on functional magnetic resonance imaging (fMRI) studies of social-cognitive abilities following TBI. Sixteen studies fulfilled the inclusion criteria resulting in a total of 190 patients with TBI and 206 controls enrolled in the ALE meta-analysis. The temporoparietal junction (TPJ) and the medial prefrontal cortex (mPFC) were the specific regions that social cognition predominantly engaged. The cingulate gyrus, frontal gyrus and inferior parietal lobule were the main regions related to social attention/executive functions. Communication dysfunction, especially related to language deficits, was found to show greater activation of the temporal gyrus and fusiform gyrus in TBI. The current ALE meta-analytic findings provide evidence that patients have significant social-cognitive disabilities following TBI. The relatively limited pool of literature and the varied fMRI results from published studies indicate that social-cognitive abilities following TBI is an area that would greatly benefit from further investigation.
Boccia, Maddalena; Piccardi, Laura; Palermo, Liana; Nori, Raffaella; Palmiero, Massimiliano
2015-01-01
Many studies have assessed the neural underpinnings of creativity, failing to find a clear anatomical localization. We aimed to provide evidence for a multi-componential neural system for creativity. We applied a general activation likelihood estimation (ALE) meta-analysis to 45 fMRI studies. Three individual ALE analyses were performed to assess creativity in different cognitive domains (Musical, Verbal, and Visuo-spatial). The general ALE revealed that creativity relies on clusters of activations in the bilateral occipital, parietal, frontal, and temporal lobes. The individual ALE revealed different maximal activation in different domains. Musical creativity yields activations in the bilateral medial frontal gyrus, in the left cingulate gyrus, middle frontal gyrus, and inferior parietal lobule and in the right postcentral and fusiform gyri. Verbal creativity yields activations mainly located in the left hemisphere, in the prefrontal cortex, middle and superior temporal gyri, inferior parietal lobule, postcentral and supramarginal gyri, middle occipital gyrus, and insula. The right inferior frontal gyrus and the lingual gyrus were also activated. Visuo-spatial creativity activates the right middle and inferior frontal gyri, the bilateral thalamus and the left precentral gyrus. This evidence suggests that creativity relies on multi-componential neural networks and that different creativity domains depend on different brain regions. PMID:26322002
Axons giving rise to the palisade endings of feline extraocular muscles display motor features.
Zimmermann, Lars; Morado-Díaz, Camilo J; Davis-López de Carrizosa, María A; de la Cruz, Rosa R; May, Paul J; Streicher, Johannes; Pastor, Ángel M; Blumer, Roland
2013-02-13
Palisade endings are nerve specializations found in the extraocular muscles (EOMs) of mammals, including primates. They have long been postulated to be proprioceptors. It was recently demonstrated that palisade endings are cholinergic and that in monkeys they originate from the EOM motor nuclei. Nevertheless, there is considerable difference of opinion concerning the nature of palisade ending function. Palisade endings in EOMs were examined in cats to test whether they display motor or sensory characteristics. We injected an anterograde tracer into the oculomotor or abducens nuclei and combined tracer visualization with immunohistochemistry and α-bungarotoxin staining. Employing immunohistochemistry, we performed molecular analyses of palisade endings and trigeminal ganglia to determine whether cat palisade endings are a cholinergic trigeminal projection. We confirmed that palisade endings are cholinergic and showed, for the first time, that they, like extraocular motoneurons, are also immunoreactive for calcitonin gene-related peptide. Following tracer injection into the EOM nuclei, we observed tracer-positive palisade endings that exhibited choline acetyl transferase immunoreactivity. The tracer-positive nerve fibers supplying palisade endings also established motor terminals along the muscle fibers, as demonstrated by α-bungarotoxin. Neither the trigeminal ganglion nor the ophthalmic branch of the trigeminal nerve contained cholinergic elements. This study confirms that palisade endings originate in the EOM motor nuclei and further indicates that they are extensions of the axons supplying the muscle fiber related to the palisade. The present work excludes the possibility that they receive cholinergic trigeminal projections. These findings call into doubt the proposed proprioceptive function of palisade endings.
Axons Giving Rise to the Palisade Endings of Feline Extraocular Muscles Display Motor Features
Zimmermann, Lars; Morado-Díaz, Camilo J.; de Carrizosa, María A. Davis-López; de la Cruz, Rosa R.; May, Paul J.; Streicher, Johannes; Pastor, Ángel M.; Blumer, Roland
2016-01-01
Palisade endings are nerve specializations found in the extraocular muscles (EOMs) of mammals, including primates. They have long been postulated to be proprioceptors. It was recently demonstrated that palisade endings are cholinergic and that in monkeys they originate from the EOM motor nuclei. Nevertheless, there is considerable difference of opinion concerning the nature of palisade ending function. Palisade endings in EOMs were examined in cats to test whether they display motor or sensory characteristics. We injected an anterograde tracer into the oculomotor or abducens nuclei and combined tracer visualization with immunohistochemistry and α-bungarotoxin staining. Employing immunohistochemistry, we performed molecular analyses of palisade endings and trigeminal ganglia to determine whether cat palisade endings are a cholinergic trigeminal projection. We confirmed that palisade endings are cholinergic and showed, for the first time, that they, like extraocular motoneurons, are also immunoreactive for calcitonin gene-related peptide. Following tracer injection into the EOM nuclei, we observed tracer-positive palisade endings that exhibited choline acetyl transferase immunoreactivity. The tracer-positive nerve fibers supplying palisade endings also established motor terminals along the muscle fibers, as demonstrated by α-bungarotoxin. Neither the trigeminal ganglion nor the ophthalmic branch of the trigeminal nerve contained cholinergic elements. This study confirms that palisade endings originate in the EOM motor nuclei and further indicates that they are extensions of the axons supplying the muscle fiber related to the palisade. The present work excludes the possibility that they receive cholinergic trigeminal projections. These findings call into doubt the proposed proprioceptive function of palisade endings. PMID:23407938
Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache
Oshinsky, Michael L.; Sanghvi, Menka M.; Maxwell, Christina R.; Gonzalez, Dorian; Spangenberg, Rebecca J.; Cooper, Marnie; Silberstein, Stephen D.
2014-01-01
Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment. PMID:22963523
Role of transcutaneous electric nerve stimulation in the management of trigeminal neuralgia
Singla, Sanju; Prabhakar, Vikram; Singla, Rajan Kumar
2011-01-01
Background: Trigeminal neuralgia typically involves nerves supplying teeth, jaws and face of older females. Though the etiology is usually obscure, different treatment modalities have been tried for it viz. medicinal treatment, injection alcohol, peripheral neurectomy, rhizotomy, and microvascular decompression etc. Transcutaneous electric nerve stimulation (TENS) is an emerging and promising option for management of such patients. Aims and Design: The present study was designed with an aim to study the efficacy of TENS in management of trigeminal neuralgia. Materials and Methods: The study was conducted on 30 patients of trigeminal neuralgia confirmed by diagnostic nerve block. They were given bursts of TENS for 20-40 days over the path of the affected nerve and subsequently evaluated at 1 month and 3 month intervals by visual analogue scale (VAS), verbal pain scale (VPS), a functional outcome scales for main daily activities like sleep, chewing, talking, or washing face. Results: The results showed that, on VAS, the score decreased from 8.9 (Pre TENS) to 3.1 at 1 month and 1.3 at 3 months, and on VPS, the score decreased from 3.5 (Pre TENS) to 1.2 at 1 month and 0.3 at 3 months. Similarly, a considerable decrease in scores was seen on functional outcome scale for different activities. No side effects like irritation or redness of skin were seen in any of the patients. Conclusions: Thus, TENS was found to be a safe, easily acceptable, and non-invasive outdoor patient department procedure for management of trigeminal neuralgia. PMID:21897677
Kakita, Kaede; Tsubouchi, Hirona; Adachi, Mayu; Takehana, Shiori; Shimazu, Yoshihito; Takeda, Mamoru
2017-11-29
Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate potassium channel conductance and acid-sensing ion channels (ASICs) in the primary sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical stimulation of trigeminal neuronal activity remains to be determined. The present study investigated whether local administration of CGA in vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuronal activity elicited by non-noxious and noxious orofacial mechanical stimulation in pentobarbital anesthetized rats. The mean number of SpVc WDR neuronal firings responding to both non-noxious and noxious mechanical stimuli were significantly and dose-dependently inhibited by local subcutaneous administration of CGA (0.1-10mM), with the maximal inhibition of discharge frequency revealed within 10min and reversed after approximately 30min. The mean frequency of SpVc neuronal discharge inhibition by CGA was comparable to that by a local anesthetic, the sodium channel blocker, 1% lidocaine. These results suggest that local CGA injection into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via the activation of voltage-gated potassium channels and modulation of ASICs in the nociceptive nerve terminal of trigeminal ganglion neurons. Therefore, local injection of CGA could contribute to local anesthetic agents for the treatment of trigeminal nociceptive pain. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
de Tommaso, M; Ricci, K; Montemurno, A; Vecchio, E
2017-07-01
This study aimed to evaluate age-related changes in laser-evoked potential (LEP) features, including habituation, via trigeminal and hand stimulation in a large group of healthy volunteers. We recorded the LEPs by right-hand stimulation in 237 healthy subjects and by stimulation of the right supraorbital zone in 170 cases. The subjects ranged in age from 7 to 72 years and were divided into six groups by age. At the trigeminal level, the N2 and P2 latencies were significantly shorter and the N2-P2 amplitude was significantly larger in the 7-17 age group than in the other groups. The N2-P2 amplitude of the responses evoked by hand stimulation was significantly larger in the 7-40 age range than in the older subjects. The N1 amplitude and latency were not significantly different among the groups. The N2-P2 habituation increased with age, but no significant changes among groups were revealed by the Bonferroni test. Trigeminal vertex LEPs have greater amplitudes and appear earlier in children, while a progressive age-related amplitude decrease characterizes the N2-P2 waves associated with hand stimulation. The N2-P2 habituation increases in older people. The N1 latency and amplitude seem to remain stable during ageing and are therefore potentially reliable and useful patterns for nociceptive system examination. Standardization of age-related changes in trigeminal and hand LEPs is possible and should improve their reliability in the objective assessment of pain pathways. © 2017 European Pain Federation - EFIC®.
Organization of the spinal trigeminal nucleus in star-nosed moles.
Sawyer, Eva K; Leitch, Duncan B; Catania, Kenneth C
2014-10-01
Somatosensory inputs from the face project to multiple regions of the trigeminal nuclear complex in the brainstem. In mice and rats, three subdivisions contain visible representations of the mystacial vibrissae, the principal sensory nucleus, spinal trigeminal subnucleus interpolaris, and subnucleus caudalis. These regions are considered important for touch with high spatial acuity, active touch, and pain and temperature sensation, respectively. Like mice and rats, the star-nosed mole (Condylura cristata) is a somatosensory specialist. Given the visible star pattern in preparations of the star-nosed mole cortex and the principal sensory nucleus, we hypothesized there were star patterns in the spinal trigeminal nucleus subnuclei interpolaris and caudalis. In sections processed for cytochrome oxidase, we found star-like segmentation consisting of lightly stained septa separating darkly stained patches in subnucleus interpolaris (juvenile tissue) and subnucleus caudalis (juvenile and adult tissue). Subnucleus caudalis represented the face in a three-dimensional map, with the most anterior part of the face represented more rostrally than posterior parts of the face. Multiunit electrophysiological mapping was used to map the ipsilateral face. Ray-specific receptive fields in adults matched the CO segmentation. The mean areas of multiunit receptive fields in subnucleus interpolaris and caudalis were larger than previously mapped receptive fields in the mole's principal sensory nucleus. The proportion of tissue devoted to each ray's representation differed between the subnucleus interpolaris and the principal sensory nucleus. Our finding that different trigeminal brainstem maps can exaggerate different parts of the face could provide new insights for the roles of these different somatosensory stations. © 2014 Wiley Periodicals, Inc.
Organization of the spinal trigeminal nucleus in Star-Nosed Moles
Sawyer, Eva K.; Leitch, Duncan B.; Catania, Kenneth C.
2014-01-01
Somatosensory inputs from the face project to multiple regions of the trigeminal nuclear complex in the brainstem. In mice and rats three subdivisions contain visible representations of the mystacial vibrissae: the principal sensory nucleus, the spinal trigeminal subnucleus interpolaris and subnucleus caudalis. These regions are considered important for touch with high spatial acuity, active touch, and pain and temperature sensation, respectively. Like mice and rats, the star-nosed mole (Condylura cristata) is a somatosensory specialist. Given the visible star pattern in preparations of the star-nosed mole cortex and the principal sensory nucleus, we hypothesized there were star patterns in the spinal trigeminal nucleus subnuclei interpolaris and caudalis. In sections processed for cytochrome oxidase we found star-like segmentation consisting of lightly stained septa separating darkly stained patches in subnucleus interpolaris (juvenile tissue) and subnucleus caudalis (juvenile and adult tissue). Subnucleus caudalis represented the face in a three-dimensional map with the most anterior part of the face represented more rostrally than posterior parts of the face. Multi-unit electrophysiological mapping was used to map the ipsilateral face. Ray-specific receptive fields in adults matched the CO-segmentation. The mean areas of multiunit receptive fields in subnucleus interpolaris and caudalis were larger than previously mapped receptive fields in the mole's principal sensory nucleus. The proportion of tissue devoted to each ray's representation differed between subnucleus interpolaris and the principal sensory nucleus. Our finding that different trigeminal brainstem maps can exaggerate different parts of the face could provide new insights for the roles of these different somatosensory stations. PMID:24715542
Ban, Ryokuya; Matsuo, Kiyoshi; Ban, Midori; Yuzuriha, Shunsuke
2013-01-01
The mixed levator and frontalis muscles lack the interior muscle spindles normally required to induce involuntary contraction of their slow-twitch fibers. To involuntarily move the eyelid and eyebrow, voluntary contraction of the levator nonskeletal fast-twitch muscle fibers stretches the mechanoreceptors in Müller's muscle to evoke trigeminal proprioception, which then induces reflex contraction of the levator and frontalis skeletal slow-twitch muscle fibers. The trigeminal proprioceptive nerve has a long intraorbital course from the mechanoreceptors in Müller's muscle to the superior orbital fissure. Since external force to the globe may cause impairment of trigeminal proprioceptive evocation, we confirmed how unilateral blowout fracture due to a hydraulic mechanism affects ipsilateral eyebrow movement as compared with unilateral zygomatic fracture. In 16 unilateral blowout fracture patients, eyebrow heights were measured on noninjured and injured sides in primary and 60° upward gaze and statistically compared. Eyebrow heights were also measured in primary gaze in 24 unilateral zygomatic fracture patients and statistically compared. In the blowout fracture patients, eyebrow heights on the injured side were significantly smaller than on the noninjured side in both gaze. In the zygomatic fracture patients, eyebrow heights on the injured side were significantly larger than on the noninjured side in primary gaze. Since 60° upward gaze did not recover the eyebrow ptosis observed in primary gaze in blowout fracture patients, such ptosis indicated impairment of trigeminal proprioceptive evocation and the presence of a hydraulic mechanism that may require ophthalmic examination.
Ban, Ryokuya; Matsuo, Kiyoshi; Ban, Midori; Yuzuriha, Shunsuke
2013-01-01
Objective: The mixed levator and frontalis muscles lack the interior muscle spindles normally required to induce involuntary contraction of their slow-twitch fibers. To involuntarily move the eyelid and eyebrow, voluntary contraction of the levator nonskeletal fast-twitch muscle fibers stretches the mechanoreceptors in Müller's muscle to evoke trigeminal proprioception, which then induces reflex contraction of the levator and frontalis skeletal slow-twitch muscle fibers. The trigeminal proprioceptive nerve has a long intraorbital course from the mechanoreceptors in Müller's muscle to the superior orbital fissure. Since external force to the globe may cause impairment of trigeminal proprioceptive evocation, we confirmed how unilateral blowout fracture due to a hydraulic mechanism affects ipsilateral eyebrow movement as compared with unilateral zygomatic fracture. Methods: In 16 unilateral blowout fracture patients, eyebrow heights were measured on noninjured and injured sides in primary and 60° upward gaze and statistically compared. Eyebrow heights were also measured in primary gaze in 24 unilateral zygomatic fracture patients and statistically compared. Results: In the blowout fracture patients, eyebrow heights on the injured side were significantly smaller than on the noninjured side in both gaze. In the zygomatic fracture patients, eyebrow heights on the injured side were significantly larger than on the noninjured side in primary gaze. Conclusion: Since 60° upward gaze did not recover the eyebrow ptosis observed in primary gaze in blowout fracture patients, such ptosis indicated impairment of trigeminal proprioceptive evocation and the presence of a hydraulic mechanism that may require ophthalmic examination. PMID:23814636
Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf; Edvinsson, Lars
2015-01-01
Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.
Lukács, M; Warfvinge, K; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L
2017-12-01
Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C 1 -C 2 regions of the spinal cord. We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C 1 -C 2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.
Results of Percutaneous Balloon Compression in Trigeminal Pain Syndromes.
Grewal, Sanjeet S; Kerezoudis, Panagiotis; Garcia, Oscar; Quinones-Hinojosa, Alfredo; Reimer, Ronald; Wharen, Robert E
2018-06-01
To investigate initial pain relief and subsequent recurrence after percutaneous balloon compression (PBC) and describe its association with the nature of trigeminal pain, previous procedures, or other clinical factors. A total of 222 patients with medically refractory trigeminal pain treated with PBC at Mayo Clinic Florida between 1998 and 2017 were enrolled into this study. Patients were divided into those with typical trigeminal neuralgia (TN) and those with atypical trigeminal pain. The postprocedural rate of pain recurrence and associations between patient characteristics and recurrence were studied. One hundred fifty-two patients had TN and 70 patients had atypical pain. At the last follow-up, 158 patients had excellent pain relief, 37 had good pain relief, 11 had fair pain relief, and 16 had poor pain relief. The median duration of follow-up was 31.1 months. Patients with atypical pain were less likely to have an excellent result compared with patients with typical pain (61.4% vs. 82.9%; P < 0.001). Recurrence was observed in 103 patients (46.4%) and was associated with previous procedures (hazard ratio, 1.658; 95% confidence interval, 1.09-2.49; P = 0.017). Other clinical factors were not significant. Our study demonstrates the safety and efficacy of PBC, with 88% of patients pain-free at last follow-up. Patients with atypical pain have worse outcomes, and patients with previous procedures have a higher risk of recurrence. Repeat surgery does not decrease efficacy. We recommend conservative parameter selection at the initial procedure. Copyright © 2018 Elsevier Inc. All rights reserved.
Singh, Harminder; da Silva, Harley Brito; Zeinalizadeh, Mehdi; Elarjani, Turki; Straus, David; Sekhar, Laligam N
2018-02-01
Microvascular decompression for patients with trigeminal neuralgia (TGN) is widely accepted as one of the modalities of treatment. The standard approach has been retrosigmoid suboccipital craniotomy with placement of a Teflon pledget to cushion the trigeminal nerve from the offending artery, or cauterize and divide the offending vein(s). However, in cases of severe compression caused by a large artery, the standard decompression technique may not be effective. To describe a unique technique of vasculopexy of the ectatic basilar artery to the tentorium in a patient with TGN attributed to a severely ectatic and tortuous basilar artery. A case series of patients who underwent this technique of vasculopexy for arterial compression is presented. The patient underwent a subtemporal transtentorial approach and the basilar artery was mobilized away from the trigeminal nerve. A suture was then passed through the wall of the basilar artery (tunica media) and secured to the tentorial edge, to keep the artery away from the nerve. The neuralgia was promptly relieved after the operation, with no complications. A postoperative magnetic resonance imaging scan showed the basilar artery to be away from the trigeminal root. In a series of 7 patients who underwent this technique of vasculopexy, no arterial complications were noted at short- or long-term follow-up. Repositioning and vasculopexy of an ectatic basilar artery for the treatment of TGN is safe and effective. This technique can also be used for other neuropathies that result from direct arterial compression. Copyright © 2017 by the Congress of Neurological Surgeons
Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats.
Yoon, Jeong-Ho; Son, Jo-Young; Kim, Min-Ji; Kang, Song-Hee; Ju, Jin-Sook; Bae, Yong-Chul; Ahn, Dong-Kuk
2018-05-01
The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.
Durham, Zachary L.; Hawkins, Jordan L.; Durham, Paul L.
2016-01-01
Objective Elevated levels of tumor necrosis factor-alpha (TNF-α) in the capsule of the temporomandibular joint (TMJ) are implicated in the underlying pathology of temporomandibular disorders (TMD). TMD are a group of conditions that result in pain in the TMJ and/or muscles of mastication, and are associated with significant social and economic burdens. The goal of this study was to investigate the effect of elevated TNF-α levels in the TMJ capsule on nocifensive behavioral response to mechanical stimulation of trigeminal neurons and regulation of cytokines within the trigeminal ganglion. Design Male Sprague-Dawley rats were injected bilaterally in the TMJ capsule with TNF-α and changes in nocifensive head withdrawal responses to mechanical stimulation of cutaneous tissue directly over the capsule was determined using von Frey filaments. Cytokine levels in trigeminal ganglia were determined by protein array analysis at several time points post injection and correlated to nocifensive behavior. Results TNF-α caused a significant increase in the average number of nocifensive responses when compared to naive and vehicle treated animals 2 hours post injection, but levels returned to control levels at 24 hours. Based on array analysis, the levels of eight cytokines were significantly elevated above vehicle control levels at 2 hours following TNF-α injection, but all eight had returned to the vehicle control levels after 24 hours. Conclusions Our findings provide evidence that elevated levels of TNF-α in the joint capsule, which is reported to occur in TMD, promotes nociception in trigeminal ganglia neurons via a mechanism that temporally correlates with differential regulation of several cytokines. PMID:27836101
The Influence of Trigeminal Stimulation on Children's Judgements of Odor.
ERIC Educational Resources Information Center
Engen, Trygg; Moskowitz, Linda
Children's preference for odors, some of which presumably had marked trigeminal (noxious) effects, was assessed with the use of the method of pair comparison. Although the children, from 4 to 7 years old, were able to discriminate between the intensities of the odors, they were neither attracted nor repelled by them as much as the adults. In other…
Evidence for a Role of Connexin 43 in Trigeminal Pain Using RNA Interference In Vivo
Ohara, Peter T.; Vit, Jean-Philippe; Bhargava, Aditi; Jasmin, Luc
2008-01-01
The importance of glial cells in the generation and maintenance of neuropathic pain is becoming widely accepted. We examined the role of glial-specific gap junctions in nociception in the rat trigeminal ganglion in nerve-injured and -uninjured states. The connexin 43 (Cx43) gap-junction subunit was found to be confined to the satellite glial cells (SGCs) that tightly envelop primary sensory neurons in the trigeminal ganglion and we therefore used Cx43 RNA interference (RNAi) to alter gap-junction function in SGCs. Using behavioral evaluation, together with immunocytochemical and Western blot monitoring, we show that Cx43 increased in the trigeminal ganglion in rats with a chronic constriction injury (CCI) of the infraorbital nerve. Reducing Cx43 expression using RNAi in CCI rats reduced painlike behavior, whereas in non-CCI rats, reducing Cx43 expression increased painlike behavior. The degree of painlike behavior in CCI rats and intact, Cx43-silenced rats was similar. Our results support previous suggestions that increases in glial gap junctions after nerve injury increases nociceptive behavior but paradoxically the reduction of gap junctions in normal ganglia also increases nociceptive behavior, possibly a reflection of the multiple functions performed by glia. PMID:18715894
Brazoloto, Thiago Medina; de Siqueira, Silvia Regina Dowgan Tesseroli; Rocha-Filho, Pedro Augusto Sampaio; Figueiredo, Eberval Gadelha; Teixeira, Manoel Jacobsen; de Siqueira, José Tadeu Tesseroli
2017-05-01
Surgical trauma at the temporalis muscle is a potential cause of post-craniotomy headache and temporomandibular disorders (TMD). The aim of this study was to evaluate the prevalence of pain, masticatory dysfunction and trigeminal somatosensory abnormalities in patients who acquired aneurysms following pterional craniotomy. Fifteen patients were evaluated before and after the surgical procedure by a trained dentist. The evaluation consisted of the (1) research diagnostic criteria for TMD, (2) a standardized orofacial pain questionnaire and (3) a systematic protocol for quantitative sensory testing (QST) for the trigeminal nerve. After pterional craniotomy, 80% of the subjects, 12 patients, developed orofacial pain triggered by mandibular function. The pain intensity was measured by using the visual analog scale (VAS), and the mean pain intensity was 3.7. The prevalence of masticatory dysfunction was 86.7%, and there was a significant reduction of the maximum mouth opening. The sensory evaluation showed tactile and thermal hypoesthesia in the area of pterional access in all patients. There was a high frequency of temporomandibular dysfunction, postoperative orofacial pain and trigeminal sensory abnormalities. These findings can help to understand several abnormalities that can contribute to postoperative headache or orofacial pain complaints after pterional surgeries.
Trigeminal neuralgia and chiropractic care: a case report
Rodine, Robert J; Aker, Peter
2010-01-01
The following case describes a 68 year-old woman with a 7½ year history of worsening head and neck pain diagnosed as trigeminal neuralgia following surgical resection of a brain tumor. After years of unsuccessful management with medication and physical therapies, a therapeutic trial of chiropractic was carried out. Chiropractic care included ultrasound, manual therapies (manipulation and mobilization), soft tissue therapies, and home stretching exercises. After an initial treatment period followed by 18 months of supportive care the patient reported satisfactory improvement. It became evident that there were at least three sources of her symptoms: mechanical and/or degenerative neck pain, temporomandibular joint syndrome, and trigeminal neuralgia. While never completely pain-free, the patient continued to report that her pains reduced to minimal at times. At the most recent follow-up, the pain had not returned to pre-treatment intractable levels. This case study demonstrates the importance of diagnosing and treating multiple sources of pain and the positive role chiropractic care can have in the management of patients with these clinical conditions. The potential for convergence of sensory input from the upper three cervical segments and the trigeminal nerve via the trigeminocervical nucleus is discussed. PMID:20808617
Bi, Rui Yun; Ding, Yun; Gan, Ye Hua
2016-03-01
To investigate the association between the analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) and sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG). Temporomandibular joint (TMJ) inflammation was induced by complete Freund's adjuvant (CFA) in female rats. Ibuprofen, diclofenac sodium and meloxicam were given intragastrically before induction of TMJ inflammation. Histopathological evaluation and scoring of TMJ inflammation was used to evaluate the level of inflammation. The head withdrawal threshold and food intake were measured to evaluate TMJ nociceptive responses. The mRNA and protein expression of trigeminal ganglionic Nav1.7 was examined using real-time polymerase chain reaction and western blot. Twenty-four hours after the injection of CFA into the TMJs, NSAIDs attenuated hyperalgesia of inflamed TMJ and simultaneously blocked inflammation-induced upregulation of Nav1.7 mRNA and protein expression in the TG. However, ibuprofen and diclofenac sodium slightly attenuated TMJ inflammation and meloxicam did not affect TMJ inflammation. Attenuation of hyperalgesia of inflamed TMJ by NSAIDs might be associated with their role in blocking upregulation of trigeminal ganglionic Nav1.7.
A second trigeminal CGRP receptor: function and expression of the AMY1 receptor
Walker, Christopher S; Eftekhari, Sajedeh; Bower, Rebekah L; Wilderman, Andrea; Insel, Paul A; Edvinsson, Lars; Waldvogel, Henry J; Jamaluddin, Muhammad A; Russo, Andrew F; Hay, Debbie L
2015-01-01
Objective The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expression and functionality of two CGRP receptor candidates in the sensory trigeminal system. Methods Receptor expression was determined using Taqman G protein-coupled receptor arrays and immunohistochemistry in trigeminal ganglia (TG) and the spinal trigeminal complex of the brainstem in rat and human. Receptor pharmacology was quantified using sensitive signaling assays in primary rat TG neurons. Results mRNA and histological expression analysis in rat and human samples revealed the presence of two CGRP-responsive receptors (AMY1: calcitonin receptor/receptor activity-modifying protein 1 [RAMP1]) and the CGRP receptor (calcitonin receptor-like receptor/RAMP1). In support of this finding, quantification of agonist and antagonist potencies revealed a dual population of functional CGRP-responsive receptors in primary rat TG neurons. Interpretation The unexpected presence of a functional non-canonical CGRP receptor (AMY1) at neural sites important for craniofacial pain has important implications for targeting the CGRP axis in migraine. PMID:26125036
Upper Cervical Spinal Cord Stimulation as an Alternative Treatment in Trigeminal Neuropathy.
Velásquez, Carlos; Tambirajoo, Kantharuby; Franceschini, Paulo; Eldridge, Paul R; Farah, Jibril Osman
2018-06-01
To describe the indications and outcomes of upper cervical cord stimulation in trigeminal neuropathy. A consecutive single-center series of patients was retrospectively reviewed. It included 12 patients with trigeminal neuropathy treated with upper cervical spinal cord stimulation. Clinical features, complications, and outcomes were reviewed. All patients had a successful trial before the definitive implantation of a spinal cord stimulator at the level of the craniocervical junction. The mean follow-up period was 4.4 years (range, 0.3-21.1 years). The average coverage in the pain zone was 72% and the median baseline, trial, and postoperative numeric rating scale (NRS) was 7, 3, and 3, respectively. When compared with the baseline, the mean reduction achieved in the postoperative average numeric rating scale was 4 points, accounting for a 57.1% pain reduction. The long-term failure rate was 25%. Despite there being enough evidence to consider upper cervical spinal cord stimulation as an effective treatment for patients with neuropathic trigeminal pain, a randomized controlled trial is needed to fully assess its indications and outcomes and compare it with other therapeutic approaches. Copyright © 2018 Elsevier Inc. All rights reserved.
No oral-cavity-only discrimination of purely olfactory odorants.
Stephenson, Dejaimenay; Halpern, Bruce P
2009-02-01
The purely olfactory odorants coumarin, octanoic acid, phenylethyl alcohol, and vanillin had been found to be consistently identified when presented retronasally but could not be identified when presented oral-cavity only (OCO). However, OCO discrimination of these odorants was not tested. Consequently, it remained possible that the oral cavity trigeminal system might provide sufficient information to differentiate these purely olfactory odorants. To evaluate this, 20 participants attempted to discriminate vapor-phase coumarin, octanoic acid, phenylethyl alcohol, and vanillin and, as a control, the trigeminal stimulus peppermint extract, from their glycerin solvent, all presented OCO. None of the purely olfactory odorants could be discriminated OCO, but, as expected, peppermint extract was consistently discriminated. This inability to discriminate clarifies and expands the previous report of lack of OCO identification of purely olfactory odorants. Taken together with prior data, these results suggest that the oral cavity trigeminal system is fully unresponsive to these odorants in vapor phase and that coumarin, octanoic acid, phenylethyl alcohol, and vanillin are indeed purely olfactory stimuli. The OCO discrimination of peppermint extract demonstrated that the absence of discrimination for the purely olfactory odorants was odorant dependent and confirmed that the oral cavity trigeminal system will provide differential response information to some vapor-phase stimuli.
JNK1 regulates histone acetylation in trigeminal neurons following chemical stimulation
Wu, Jing; Zhang, Xuan; Nauta, Haring J; Lin, Qing; Li, Junfa; Fang, Li
2008-01-01
Trigeminal nerve fibers in nasal and oral cavities are sensitive to various environmental hazardous stimuli, which trigger many neurotoxic problems such as chronic migraine headache and trigeminal irritated disorders. However, the role of JNK kinase cascade and its epigenetic modulation of histone remodeling in trigeminal ganglion (TG) neurons activated by environmental neurotoxins remains unknown. Here we investigated the role of JNK/c-Jun cascade in the regulation of acetylation of H3 histone in TG neurons following in vitro stimulation by a neuro-inflammatory agent, mustard oil (MO). We found that MO stimulation elicited JNK/c-Jun pathway significantly by enhancing phospho-JNK1, phospho-c-Jun expression, and c-Jun activity, which were correlated with an elevated acetylated H3 histone in TG neurons. However, increases in phospho-c-Jun and c-Jun activity were significantly blocked by a JNK inhibitor, SP600125. We also found that altered H3 histone remodeling, assessed by H3 acetylation in triggered TG neurons, was reduced by SP600125. The study suggests that the activated JNK signaling in regulation of histone remodeling may contribute to neuro-epigentic changes in peripheral sensory neurons following environmental neurotoxic exposure. PMID:18822271
Hernández, C. J.; Ortíz, T.; Foster, C. Rosa K.; Tyagi, M; Lugo, N.; Albrecht, R.; Chinapen, S.
2007-01-01
Mucociliary activity is an important clearance mechanism in the respiratory system of air breathing vertebrates. Substance P (SP) and acetylcholine play a key role in the stimulation of the mucociliary transport in the frog palate. In this study, retrograde neuronal tracing was combined with immunocytochemistry for SP and choline acetyl transferase (ChAT) in the trigeminal ganglion and for neurokinin-1 receptor (NK1R) in the palate of Rana pipiens. The cells of origin of the palatine nerve were identified in the trigeminal ganglion using the retrograde tracer Fluorogold (FG). Optimal labeling of FG cells in the trigeminal ganglion was obtained at 96 h of exposure. Immunoflorescent shows that SP and acetylcholine are co-localized in 92% of the cells labeled with FG in the trigeminal ganglion. NK1 receptors were found in the membrane of epithelial and goblet cells of the palate. Ultrastructural study of the palate showed axonal-like endings with vesicles in connection with epithelial and goblet cells. These results further support the concerted action of both neurotransmitters in the regulation of mucociliary activity in the frog palate. PMID:17276713
Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge.
Ang, Jensen W J; Khanna, Arjun; Walcott, Brian P; Kahle, Kristopher T; Eskandar, Emad N
2015-07-01
We describe an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel's cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intracranial tumors, but its incidence has been steadily increasing in some groups [1]. It usually arises in the periventricular cerebral white matter, and reports of lymphoma in extra-axial regions are rare [2]. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-01
... 1. JIM'ALE, Ahmed Nur Ali (a.k.a. JIMALE, Ahmad Ali; a.k.a. JIM'ALE, Ahmad Nur Ali; a.k.a. JIMALE, Ahmed Ali; a.k.a. JIMALE, Shaykh Ahmed Nur; a.k.a. JIMALE, Sheikh Ahmed; a.k.a. JUMALE, Ahmed Ali; a.k.a. JUMALE, Ahmed Nur; a.k.a. JUMALI, Ahmed Ali), P.O. Box 3312, Dubai, United Arab Emirates; Mogadishu...
2013-01-01
Based Micropolar Single Crystal Plasticity: Comparison of Multi - and Single Criterion Theories. J. Mech. Phys. Solids 2011, 59, 398–422. ALE3D ...element boundaries in a multi -step constitutive evaluation (Becker, 2011). The results showed the desired effects of smoothing the deformation field...Implementation The model was implemented in the large-scale parallel, explicit finite element code ALE3D (2012). The crystal plasticity
Performance evaluation of a mobile satellite system modem using an ALE method
NASA Technical Reports Server (NTRS)
Ohsawa, Tomoki; Iwasaki, Motoya
1990-01-01
Experimental performance of a newly designed demodulation concept is presented. This concept applies an Adaptive Line Enhancer (ALE) to a carrier recovery circuit, which makes pull-in time significantly shorter in noisy and large carrier offset conditions. This new demodulation concept was actually developed as an INMARSAT standard-C modem, and was evaluated. On a performance evaluation, 50 symbol pull-in time is confirmed under 4 dB Eb/No condition.
Targeted delivery of mesenchymal stem cells to the bone.
Yao, Wei; Lane, Nancy E
2015-01-01
Osteoporosis is a disease of excess skeletal fragility that results from estrogen loss and aging. Age related bone loss has been attributed to both elevated bone resorption and insufficient bone formation. We developed a hybrid compound, LLP2A-Ale in which LLP2A has high affinity for the α4β1 integrin on mesenchymal stem cells (MSCs) and alendronate has high affinity for bone. When LLP2A-Ale was injected into mice, the compound directed MSCs to both trabecular and cortical bone surfaces and increased bone mass and bone strength. Additional studies are underway to further characterize this hybrid compound, LLP2A-Ale, and how it can be utilized for the treatment of bone loss resulting from hormone deficiency, aging, and inflammation and to augment bone fracture healing. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.
Chao, Chun-Tang; Maneetien, Nopadon; Wang, Chi-Jo; Chiou, Juing-Shian
2014-01-01
This paper presents the design and evaluation of the hardware circuit for electronic stethoscopes with heart sound cancellation capabilities using field programmable gate arrays (FPGAs). The adaptive line enhancer (ALE) was adopted as the filtering methodology to reduce heart sound attributes from the breath sounds obtained via the electronic stethoscope pickup. FPGAs were utilized to implement the ALE functions in hardware to achieve near real-time breath sound processing. We believe that such an implementation is unprecedented and crucial toward a truly useful, standalone medical device in outpatient clinic settings. The implementation evaluation with one Altera cyclone II-EP2C70F89 shows that the proposed ALE used 45% resources of the chip. Experiments with the proposed prototype were made using DE2-70 emulation board with recorded body signals obtained from online medical archives. Clear suppressions were observed in our experiments from both the frequency domain and time domain perspectives.
Simulating Afterburn with LLNL Hydrocodes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Daily, L D
2004-06-11
Presented here is a working methodology for adapting a Lawrence Livermore National Laboratory (LLNL) developed hydrocode, ALE3D, to simulate weapon damage effects when afterburn is a consideration in the blast propagation. Experiments have shown that afterburn is of great consequence in enclosed environments (i.e. bomb in tunnel scenario, penetrating conventional munition in a bunker, or satchel charge placed in a deep underground facility). This empirical energy deposition methodology simulates the anticipated addition of kinetic energy that has been demonstrated by experiment (Kuhl, et. al. 1998), without explicitly solving the chemistry, or resolving the mesh to capture small-scale vorticity. This effortmore » is intended to complement the existing capability of either coupling ALE3D blast simulations with DYNA3D or performing fully coupled ALE3D simulations to predict building or component failure, for applications in National Security offensive strike planning as well as Homeland Defense infrastructure protection.« less
Spontaneous behavioral responses in the orofacial region: A model of trigeminal pain in mouse
Romero-Reyes, Marcela; Akerman, Simon; Nguyen, Elaine; Vijjeswarapu, Alice; Hom, Betty; Dong, Hong-Wei; Charles, Andrew C.
2012-01-01
OBJECTIVES To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse. BACKGROUND Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology. METHODS C57BL/6 mice received either an injection of 0.9% Saline solution or complete Freund’s adjuvant (CFA) into the right masseter muscle. Animals were video recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hrs, mice were euthanized, perfused and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate, to determine the nociceptive-specific nature of their behaviors. RESULTS We characterized and quantified 3 distinct patterns of acute grooming behaviors: fore-paw rubbing, lower lip skin/cheek rubbing against enclosure floor and hind paw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. CFA-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after two hours. CONCLUSIONS These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this common and challenging condition. PMID:22830495
Cady, R J; Denson, J E; Sullivan, L Q; Durham, P L
2014-06-06
Sensitization and activation of trigeminal nociceptors is implicated in prevalent and debilitating orofacial pain conditions including temporomandibular joint (TMJ) disorders. Orexins are excitatory neuropeptides that function to regulate many physiological processes and are reported to modulate nociception. To determine the role of orexins in an inflammatory model of trigeminal activation, the effects of a dual orexin receptor antagonist (DORA-12) on levels of proteins that promote peripheral and central sensitization and changes in nocifensive responses were investigated. In adult male Sprague-Dawley rats, mRNA for orexin receptor 1 (OX₁R) and receptor 2 (OX₂R) were detected in trigeminal ganglia and spinal trigeminal nucleus (STN). OX₁R immunoreactivity was localized primarily in neuronal cell bodies in the V3 region of the ganglion and in laminas I-II of the STN. Animals injected bilaterally with complete Freund's adjuvant (CFA) in the TMJ capsule exhibited increased expression of P-p38, P-ERK, and lba1 in trigeminal ganglia and P-ERK and lba1 in the STN at 2 days post injection. However, levels of each of these proteins in rats receiving daily oral DORA-12 were inhibited to near basal levels. Similarly, administration of DORA-12 on days 3 and 4 post CFA injection in the TMJ effectively inhibited the prolonged stimulated expression of protein kinase A, NFkB, and Iba1 in the STN on day 5 post injection. While injection of CFA mediated a nocifensive response to mechanical stimulation of the orofacial region at 2h and 3 and 5 days post injection, treatment with DORA-12 suppressed the nocifensive response on day 5. Somewhat surprisingly, nocifensive responses were again observed on day 10 post CFA stimulation in the absence of daily DORA-12 administration. Our results provide evidence that DORA-12 can inhibit CFA-induced stimulation of trigeminal sensory neurons by inhibiting expression of proteins associated with sensitization of peripheral and central neurons and nociception. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
2013-01-01
Background Nitric oxide (NO) is thought to play an important role in the pathophysiology of migraine. Infusion of the nitrovasodilator glyceroltrinitrate (nitroglycerin, GTN), which mobilizes NO in the organism, is an approved migraine model in humans. Calcitonin gene-related peptide (CGRP) is regarded as another key mediator in migraine. Increased plasma levels of CGRP have been found during spontaneous as well as nitrovasodilator-induced migraine attacks. The nociceptive processes and interactions underlying the NO and CGRP mediated headache are poorly known but can be examined in animal experiments. In the present study we examined changes in immunofluorescence of CGRP receptor components (CLR and RAMP1) and soluble guanylyl cyclase (sGC), the intracellular receptor for NO, in rat trigeminal ganglia after pretreatment with GTN. Methods Isoflurane anaesthetised rats were intravenously infused with GTN (1 mg/kg) or saline for four hours and two hours later the trigeminal ganglia were processed for immunohistochemistry. Different primary antibodies recognizing CLR, RAMP1, CGRP and sGC coupled to fluorescent secondary antibodies were used to examine immunoreactive cells in serial sections of trigeminal ganglia with epifluorescence and confocal laser scanning microscopy. Several staining protocols were examined to yield optimized immunolabeling. Results In vehicle-treated animals, 42% of the trigeminal ganglion neurons were immunopositive for RAMP1 and 41% for CLR. After GTN pretreatment CLR-immunopositivity was unchanged, while there was an increase in RAMP1-immunopositive neurons to 46%. RAMP1 and CLR immunoreactivity was also detected in satellite cells. Neurons immunoreactive for sGC were on average smaller than sGC-immunonegative neurons. The percentage of sGC-immunopositive neurons (51% after vehicle) was decreased after GTN infusion (48%). Conclusions Prolonged infusion of GTN caused increased fractions of RAMP1- and decreased fractions of sGC-immunopositive neurons in the trigeminal ganglion. The observed alterations are likely immunophenotypic correlates of the pathophysiological processes underlying nitrovasodilator-induced migraine attacks and indicate that signalling via CGRP receptors but not sGC-mediated mechanisms may be enhanced through endogenous NO production. PMID:24004534
DOE Office of Scientific and Technical Information (OSTI.GOV)
Downs, Janelle L.; Durham, Robin E.; Larson, Kyle B.
The U.S. Department of Energy (DOE), Richland Operations Office is working to remove a number of facilities on the Fitzner Eberhardt Arid Lands Ecology Reserve (ALE), which is part of the Hanford Reach National Monument. Decommissioning and removal of buildings and debris on ALE will leave bare soils and excavated areas that need to be revegetated to prevent erosion and weed invasion. Four main areas within ALE are affected by these activities (DOE 2009;DOE/EA-1660F): 1) facilities along the ridgeline of Rattlesnake Mountain, 2) the former Nike missile base and ALE HQ laboratory buildings, 3) the aquatic research laboratory at Rattlesnakemore » Springs area, and 4) a number of small sites across ALE where various types of debris remain from previous uses. This revegetation plan addresses the revegetation and restoration of those land areas disturbed by decommissioning and removal of buildings, facilities and associated infrastructure or debris removal. The primary objective of the revegetation efforts on ALE is to establish native vegetation at each of the sites that will enhance and accelerate the recovery of the native plant community that naturally persists at that location. Revegetation is intended to meet the direction specified by the Environmental Assessment (DOE 2009; DOE/EA-1660F) and by Stipulation C.7 of the Memorandum of Agreement (MOA) for the Rattlesnake Mountain Combined Community Communication Facility and InfrastructureCleanup on the Fitzner/Eberhardt Arid Lands Ecology Reserve, Hanford Site, Richland Washington(DOE 2009; Appendix B). Pacific Northwest National Laboratory (PNNL) under contract with CH2M Hill Plateau Remediation Company (CPRC) and in consultation with the tribes and DOE-RL developed a site-specific strategy for each of the revegetation units identified within this document. The strategy and implementation approach for each revegetation unit identifies an appropriate native species mix and outlines the necessary site preparation activities and specific methods for seeding and planting at each area. evegetation work is scheduled to commence during the first quarter of FY 2011 to minimize the amount of time that sites are unvegetated and more susceptible to invasion by non-native weedy annual species.« less
Modeling of Complex Coupled Fluid-Structure Interaction Systems in Arbitrary Water Depth
2009-01-01
basin. For the particle finite- element method ( PFEM ) near-field fluid model we completed: (4) the development of a fully-coupled fluid/flexible...method ( PFEM ) based framework for the ALE-RANS solver [1]. We presented the theory of ALE-RANS with a k- turbulence closure model and several numerical...implemented by PFEM (Task (4)). In this work a universal wall function (UWF) is introduced and implemented to more accurately predict the boundary
2016-06-12
Particle Size in Discrete Element Method to Particle Gas Method (DEM_PGM) Coupling in Underbody Blast Simulations Venkatesh Babu, Kumar Kulkarni, Sanjay...buried in soil viz., (1) coupled discrete element & particle gas methods (DEM-PGM) and (2) Arbitrary Lagrangian-Eulerian (ALE), are investigated. The...DEM_PGM and identify the limitations/strengths compared to the ALE method. Discrete Element Method (DEM) can model individual particle directly, and
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wemhoff, A P; Burnham, A K
2006-04-05
Cross-comparison of the results of two computer codes for the same problem provides a mutual validation of their computational methods. This cross-validation exercise was performed for LLNL's ALE3D code and AKTS's Thermal Safety code, using the thermal ignition of HMX in two standard LLNL cookoff experiments: the One-Dimensional Time to Explosion (ODTX) test and the Scaled Thermal Explosion (STEX) test. The chemical kinetics model used in both codes was the extended Prout-Tompkins model, a relatively new addition to ALE3D. This model was applied using ALE3D's new pseudospecies feature. In addition, an advanced isoconversional kinetic approach was used in the AKTSmore » code. The mathematical constants in the Prout-Tompkins code were calibrated using DSC data from hermetically sealed vessels and the LLNL optimization code Kinetics05. The isoconversional kinetic parameters were optimized using the AKTS Thermokinetics code. We found that the Prout-Tompkins model calculations agree fairly well between the two codes, and the isoconversional kinetic model gives very similar results as the Prout-Tompkins model. We also found that an autocatalytic approach in the beta-delta phase transition model does affect the times to explosion for some conditions, especially STEX-like simulations at ramp rates above 100 C/hr, and further exploration of that effect is warranted.« less
Nootropic activity of tuber extract of Pueraria tuberosa (Roxb).
Rao, N Venkata; Pujar, Basavaraj; Nimbal, S K; Shantakumar, S M; Satyanarayana, S
2008-08-01
Nootropic effect of alcoholic (ALE; 50, 75, 100 mg/kg) and aqueous (AQE; 100, 200, 400 mg/kg) extracts of P. tuberosa was evaluated by using Elevated Plus Maze (EPM), scopolamine-induced amnesia (SIA), diazepam-induced amnesia (DIA), clonidine-induced (NA-mediated) hypothermia (CIH), lithium-induced (5-HT mediated) head twitches (LIH) and haloperidol-induced (DA- mediated) catalepsy (HIC) models. Piracetam was used as the standard drug. A significant increase in inflexion ratio (IR) was recorded in EPM, SIA and DIA models. A significant reversal effect was observed on rectal temperature in CIH model, reduction of head twitches in LIH models. However no significant reduction in catalepsy scores in HIC models were observed with test extracts and standard piracetam. The results indicate that nootropic activity observed with ALE and AQE of tuber extracts of P. tuberosa could be through improved learning and memory either by augmenting the noradrenaline (NA) transmission or by interfering with 5-hydroxytryptamine (5-HT) release. Further, the extracts neither facilitated nor blocked release of the dopamine (DA). Thus ALE and AQE elicited significant nootropic effect in mice and rats by interacting with cholinergic, GABAnergic, adrenergic and serotonergic systems. Phytoconstituents like flavonoids have been reported for their nootropic effect and these are present in both ALE and AQE extracts of tubers of P. tuberosa (Roxb) and these active principles may be responsible for nootropic activity.
Voziyan, Paul A; Metz, Thomas O; Baynes, John W; Hudson, Billy G
2002-02-01
Reactive carbonyl compounds are formed during autoxidation of carbohydrates and peroxidation of lipids. These compounds are intermediates in the formation of advanced glycation end products (AGE) and advanced lipoxidation end products (ALE) in tissue proteins during aging and in chronic disease. We studied the reaction of carbonyl compounds glyoxal (GO) and glycolaldehyde (GLA) with pyridoxamine (PM), a potent post-Amadori inhibitor of AGE formation in vitro and of development of renal and retinal pathology in diabetic animals. PM reacted rapidly with GO and GLA in neutral, aqueous buffer, forming a Schiff base intermediate that cyclized to a hemiaminal adduct by intramolecular reaction with the phenolic hydroxyl group of PM. This bicyclic intermediate dimerized to form a five-ring compound with a central piperazine ring, which was characterized by electrospray ionization-liquid chromatography/mass spectrometry, NMR, and x-ray crystallography. PM also inhibited the modification of lysine residues and loss of enzymatic activity of RNase in the presence of GO and GLA and inhibited formation of the AGE/ALE N(epsilon)-(carboxymethyl)lysine during reaction of GO and GLA with bovine serum albumin. Our data suggest that the AGE/ALE inhibitory activity and the therapeutic effects of PM observed in diabetic animal models depend, at least in part, on its ability to trap reactive carbonyl intermediates in AGE/ALE formation, thereby inhibiting the chemical modification of tissue proteins.
Ben Salem, Maryem; Athmouni, Khaled; Ksouda, Kamilia; Dhouibi, Raouia; Sahnoun, Zouheir; Hammami, Serria; Zeghal, Khaled Mounir
2017-01-01
Objective. Artichoke (Cynara scolymus L.) was one of the plant remedies for primary health care. The present study was focused on the determination of chemical composition, antioxidant activities, and anti-inflammatory activity and on analyzing its major bioactive polyphenols by HPLC. Methods. Artichoke Leaves Extracts (ALE) were analyzed for proximate analysis and phytochemical and antioxidant activity by several methods such as DDPH, ABTS, FRAP, and beta-carotene bleaching test. The carrageenan (Carr) model induced paw oedema in order to investigate the anti-inflammatory activity. Identification and quantification of bioactive polyphenols compounds were done by HPLC method. The oxidative stress parameters were determined; CAT, SOD, GSH, MDA, and AOPP activities and the histopathological examination were also performed. Results. It was noted that EtOH extract of ALE contained the highest phenolic, flavonoid, and tannin contents and the strongest antioxidants activities including DDPH (94.23%), ABTS (538.75 mmol), FRAP assay (542.62 umol), and β-carotene bleaching (70.74%) compared to the other extracts of ALE. Administration of EtOH extract at dose 400 mg/kg/bw exhibited a maximum inhibition of inflammation induced by Carr for 3 and 5 hours compared to reference group Indomethacin (Indo). Conclusion. ALE displayed high potential as natural source of minerals and phytochemicals compounds with antioxidant and anti-inflammatory properties. PMID:28539965
Ben Salem, Maryem; Affes, Hanen; Athmouni, Khaled; Ksouda, Kamilia; Dhouibi, Raouia; Sahnoun, Zouheir; Hammami, Serria; Zeghal, Khaled Mounir
2017-01-01
Objective . Artichoke ( Cynara scolymus L.) was one of the plant remedies for primary health care. The present study was focused on the determination of chemical composition, antioxidant activities, and anti-inflammatory activity and on analyzing its major bioactive polyphenols by HPLC. Methods . Artichoke Leaves Extracts (ALE) were analyzed for proximate analysis and phytochemical and antioxidant activity by several methods such as DDPH, ABTS, FRAP, and beta-carotene bleaching test. The carrageenan (Carr) model induced paw oedema in order to investigate the anti-inflammatory activity. Identification and quantification of bioactive polyphenols compounds were done by HPLC method. The oxidative stress parameters were determined; CAT, SOD, GSH, MDA, and AOPP activities and the histopathological examination were also performed. Results . It was noted that EtOH extract of ALE contained the highest phenolic, flavonoid, and tannin contents and the strongest antioxidants activities including DDPH (94.23%), ABTS (538.75 mmol), FRAP assay (542.62 umol), and β -carotene bleaching (70.74%) compared to the other extracts of ALE. Administration of EtOH extract at dose 400 mg/kg/bw exhibited a maximum inhibition of inflammation induced by Carr for 3 and 5 hours compared to reference group Indomethacin (Indo). Conclusion . ALE displayed high potential as natural source of minerals and phytochemicals compounds with antioxidant and anti-inflammatory properties.
Microbial diversity and metabolite composition of Belgian red-brown acidic ales.
Snauwaert, Isabel; Roels, Sanne P; Van Nieuwerburg, Filip; Van Landschoot, Anita; De Vuyst, Luc; Vandamme, Peter
2016-03-16
Belgian red-brown acidic ales are sour and alcoholic fermented beers, which are produced by mixed-culture fermentation and blending. The brews are aged in oak barrels for about two years, after which mature beer is blended with young, non-aged beer to obtain the end-products. The present study evaluated the microbial community diversity of Belgian red-brown acidic ales at the end of the maturation phase of three subsequent brews of three different breweries. The microbial diversity was compared with the metabolite composition of the brews at the end of the maturation phase. Therefore, mature brew samples were subjected to 454 pyrosequencing of the 16S rRNA gene (bacteria) and the internal transcribed spacer region (yeasts) and a broad range of metabolites was quantified. The most important microbial species present in the Belgian red-brown acidic ales investigated were Pediococcus damnosus, Dekkera bruxellensis, and Acetobacter pasteurianus. In addition, this culture-independent analysis revealed operational taxonomic units that were assigned to an unclassified fungal community member, Candida, and Lactobacillus. The main metabolites present in the brew samples were L-lactic acid, D-lactic acid, and ethanol, whereas acetic acid was produced in lower quantities. The most prevailing aroma compounds were ethyl acetate, isoamyl acetate, ethyl hexanoate, and ethyl octanoate, which might be of impact on the aroma of the end-products. Copyright © 2016 Elsevier B.V. All rights reserved.
Shrub-Steppe Seasons A Natural History of the Mid-Columbia Basin
DOE Office of Scientific and Technical Information (OSTI.GOV)
LE Rogers
1995-08-01
This book collects and updates a series of articles about the natural history of the Mid-Columbia region. The articles first appeared as a monthly column titled ''Natural History'' in the Tri-City Herald, beginning in May 1991. My approach has been to condense the best of what is known about the ecology of the region to a manageable length with little in the way of technical language and terms. Admittedly, there is a bias toward those topics and species on which I have either been personally involved or observed as part of the ecology research programs conducted on the Fitzner/Eberhardt Aridmore » Lands Ecology (ALE) Reserve. The ALE Reserve is situated on the northeast-facing flank of the Rattlesnake Hills. Rattlesnake Mountain with a crest of over 3,600 feet is visible throughout much of the Mid-Columbia. Shrub-steppe grasslands once covered a large part of the western United States but most have been converted to other uses. The ALE site is the only remaining sizeable acreage (120 square miles) that is in near pristine condition and provides the only clear indication as to what the early trappers, traders, pioneers, and tribal members may have encountered in their day-to-day activities. In this respect, ALE provides a visible touchstone linking the past with the present for all of us.« less
Tomić, Maja A; Pecikoza, Uroš B; Micov, Ana M; Stepanović-Petrović, Radica M
2015-12-01
Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action. The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain. ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P ≤ 0.011), in the tail-flick test in diabetic mice (P ≤ 0.013), and in the writhing test (P ≤ 0.003). GR 127935 (P ≤ 0.038) and AM251 and AM630 (P ≤ 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner. ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.
Schöbel, Nicole; Radtke, Debbie; Kyereme, Jessica; Wollmann, Nadine; Cichy, Annika; Obst, Katja; Kallweit, Kerstin; Kletke, Olaf; Minovi, Amir; Dazert, Stefan; Wetzel, Christian H; Vogt-Eisele, Angela; Gisselmann, Günter; Ley, Jakob P; Bartoshuk, Linda M; Spehr, Jennifer; Hofmann, Thomas; Hatt, Hanns
2014-07-01
Astringency is an everyday sensory experience best described as a dry mouthfeel typically elicited by phenol-rich alimentary products like tea and wine. The neural correlates and cellular mechanisms of astringency perception are still not well understood. We explored taste and astringency perception in human subjects to study the contribution of the taste as well as of the trigeminal sensory system to astringency perception. Subjects with either a lesion or lidocaine anesthesia of the Chorda tympani taste nerve showed no impairment of astringency perception. Only anesthesia of both the lingual taste and trigeminal innervation by inferior alveolar nerve block led to a loss of astringency perception. In an in vitro model of trigeminal ganglion neurons of mice, we studied the cellular mechanisms of astringency perception. Primary mouse trigeminal ganglion neurons showed robust responses to 8 out of 19 monomeric phenolic astringent compounds and 8 polymeric red wine polyphenols in Ca(2+) imaging experiments. The activating substances shared one or several galloyl moieties, whereas substances lacking the moiety did not or only weakly stimulate responses. The responses depended on Ca(2+) influx and voltage-gated Ca(2+) channels, but not on transient receptor potential channels. Responses to the phenolic compound epigallocatechin gallate as well as to a polymeric red wine polyphenol were inhibited by the Gαs inactivator suramin, the adenylate cyclase inhibitor SQ, and the cyclic nucleotide-gated channel inhibitor l-cis-diltiazem and displayed sensitivity to blockers of Ca(2+)-activated Cl(-) channels. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Trigeminal complications arising after surgery of cranial base meningiomas.
Westerlund, Ulf; Linderoth, Bengt; Mathiesen, Tiit
2012-04-01
Chronic severe facial pain is a feared sequel of cranial base surgery. This study explores the symptomatology, incidence and impact on the individual of postoperative de novo trigeminal nerve affection as well as the recovery potential. Out of 231 patients operated for cranial base meningiomas at the Karolinska University Hospital during 7 years, 25 complained of de novo trigeminal symptoms at clinical follow-up 3 months after surgery. Six were later lost to follow-up leaving 19 participants in the study, which was conducted using a questionnaire and a structured telephone interview. All patients complained of facial numbness, affecting the V1 branch in 10/19 patients (53%), the V2 branch in 18/19 (95%) and the V3 branch in 9/19 (47%). Surprisingly, only three (16%) suffered from trigeminal pain, which could be adequately managed by pharmacotherapy. However, five patients (26%) demonstrated ocular dysaesthetic problems. Twelve (63%) described their handicap to be mild, while seven (37%) had daily or severe symptoms. Five patients (26%) reported no improvement over time, while nine (47%) showed improvement and four (21%) stated good recovery. Only one patient (5%) claimed complete symptom remission. In the present study, 11% of the patients presented with a de novo postoperative affection of the trigeminal nerve after removal of a cranial base meningioma; 37% of these reported daily/severe symptoms. Only 26% showed good recovery, observed in patients without tumour infiltration of the nerve or intraoperative nerve damage. In spite of frequent complaints of numbness, pain was uncommon (16%) and often manageable by pharmacotherapy, while ocular symptoms turned out to be more frequent and more disabling than expected.
Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D
2014-04-01
Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®
Broggi, G; Ferroli, P; Franzini, A; Servello, D; Dones, I
2000-01-01
To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24 months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits.
Broggi, G.; Ferroli, P.; Franzini, A.; Servello, D.; Dones, I.
2000-01-01
OBJECTIVE—To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. METHODS—Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. RESULTS—Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. CONCLUSIONS—Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits. PMID:10601403
An experimental animal model for percutaneous procedures used in trigeminal neuralgia.
Herta, Johannes; Wang, Wei-Te; Höftberger, Romana; Breit, Sabine; Kneissl, Sibylle; Bergmeister, Helga; Ferraz-Leite, Heber
2017-07-01
This study describes an experimental rabbit model that allows the reproduction of percutaneous operations that are used in patients with trigeminal neuralgia (TN). Attention was given to an exact anatomical description of the rabbit's middle cranial fossa as well as the establishment of conditions for a successful procedure. Morphometric measurements were taken from 20 rabbit skulls and CT scans. The anatomy of the trigeminal nerve, as well as its surrounding structures, was assessed by bilateral dissection of 13 New Zealand white rabbits (NWR). An ideal approach of placing a needle through the foramen ovale to reach the TG was sought. Validation of correct placement was realized by fluoroscopy and confirmed by dissection. Precise instructions for successful reproduction of percutaneous procedures in NWR were described. According to morphological measurements, for balloon compression of the trigeminal ganglion (TG) the maximal diameter of an introducing cannula is 1.85 mm. The diameter of an empty balloon catheter should not exceed 1.19 mm, and the length of the inflatable part of the balloon can range up to 4 mm. For thermocoagulation the needle electrodes must not exceed an external diameter of 1.39, mm and the length of the non-insolated tip can range up to 4 mm. Glycerol rhizolysis can be achieved because the trigeminal cistern in the NWR is a closed space that allows a long dwelling time (>10 min) of the contrast agent. An experimental NWR model intended for the reproduction of percutaneous procedures on the TG has been meticulously described. This provides a tool that enables further standardized animal research in the field of surgical treatment of TN.
Ishida, Kentaro; Saito, Tetsuichiro; Mitsui, Toshiyuki
2018-06-01
A Merkel cell-neurite complex is a touch receptor composed of specialized epithelial cells named Merkel cells and peripheral sensory nerves in the skin. Merkel cells are found in touch-sensitive skin components including whisker follicles. The nerve fibers that innervate Merkel cells of a whisker follicle extend from the maxillary branch of the trigeminal ganglion. Whiskers as a sensory organ attribute to the complicated architecture of the Merkel cell-neurite complex, and therefore it is intriguing how the structure is formed. However, observing the dynamic process of the formation of a Merkel cell-neurite complex in whiskers during embryonic development is still difficult. In this study, we tried to develop an organotypic co-culture method of a whisker pad and a trigeminal ganglion explant to form the Merkel cell-neurite complex in vitro. We initially developed two distinct culture methods of a single whisker row and a trigeminal ganglion explant, and then combined them. By dissecting and cultivating a single row from a whisker pad, the morphogenesis of whisker follicles could be observed under a microscope. After the co-cultivation of the whisker row with a trigeminal ganglion explant, a Merkel cell-neurite complex composed of Merkel cells, which were positive for both cytokeratin 8 and SOX2, Neurofilament-H-positive trigeminal nerve fibers and Schwann cells expressing Nestin, SOX2 and SOX10 was observed via immunohistochemical analyses. These results suggest that the process for the formation of a Merkel cell-neurite complex can be observed under a microscope using our organotypic co-culture method. © 2018 Japanese Society of Developmental Biologists.
Ban, Ryokuya; Matsuo, Kiyoshi; Osada, Yoshiro; Ban, Midori; Yuzuriha, Shunsuke
2010-01-01
We have proposed a hypothetical mechanism to involuntarily sustain the effective eyelid retraction, which consists of not only voluntary but also reflexive contractions of the levator palpebrae superior muscle (LPSM). Voluntary contraction of fast-twitch fibres of the LPSM stretches the mechanoreceptors in Mueller's muscle to evoke trigeminal proprioception, which induces continuous reflexive contraction of slow-twitch fibres of the LPSM through the trigeminal proprioceptive nerve fibres innervating the mechanoreceptors in Mueller's muscle via the oculomotor neurons, as a tonic trigemino-oculomotor reflex. In the common skeletal mixed muscles, electrical stimulation of the proprioceptive nerve, which apparently connects the mechanoreceptors in muscle spindles to the motoneurons, induces the electromyographic response as the Hoffmann reflex. To verify the presence of the trigemino-oculomotor reflex, we confirmed whether intra-operative electrical simulation of the transverse trigeminal proprioceptive nerve on the proximal Mueller's muscle evokes an electromyographic response in the LPSM under general anaesthesia in 12 patients. An ipsilateral, phasic, short-latency response (latency: 2.8+/-0.3 ms) was induced in the ipsilateral LPSM in 10 of 12 subjects. As successful induction of the short-latency response in the ipsilateral LPSM corresponds to the Hoffmann reflex in the common skeletal mixed muscles, the present study is the first electromyographic verification of the presence of the monosynaptic trigemino-oculomotor reflex to induce reflexive contraction of the LPSM. The presence of the trigemino-oculomotor reflex may elucidate the unexplainable blepharoptosis due to surgery, trauma and tumour, all of which may damage the trigeminal proprioceptive nerve fibres to impair the trigemino-oculomotor reflex. Copyright (c) 2008. Published by Elsevier Ltd.
Palacios Ceña, María; Castaldo, Matteo; Kelun Wang; Torelli, Paola; Pillastrini, Paolo; Fernández-de-Las-Peñas, César; Arendt-Nielsen, Lars
2017-02-01
To investigate differences in widespread pressure pain hyperalgesia in the trigemino-cervical and extra-trigeminal (distant pain-free) regions in women with frequent episodic (FETTH) and chronic (CTTH) tension-type headache. It seems that people with tension-type headache exhibit central sensitization. No study has investigated differences between FETTH and CTTH in terms of widespread pressure pain hypersensitivity. Forty-three women with FETTH, 42 with CTTH, and 45 women without headache diagnosis were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over trigeminal area (ie, temporalis muscle), extra-trigeminal (ie, C5/C6 zygapophyseal joint), and two distant points (ie, second metacarpal and tibialis anterior muscle) by a blinded assessor. Clinical features of the headache were collected with a 4-week headache diary. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). The ANCOVA revealed that PPTs were significantly decreased bilaterally over trigeminal (mean differences ranging from 97.5 to 101.5 kPa), extra-trigeminal (from 94.3 to 114.5 kPa), and distant points (from 99.4 to 208.6 kPa) in both FETTH and CTTH groups compared with controls (all, P < .001). No differences between FETTH and CTTH were observed (all points, P > .217). Anxiety (all, P > .803) or depression (P > .206) did not influence pressure pain hyperalgesia. No associations between widespread pressure hypersensitivity and headache features were observed (all, P > .110). Current results suggest the presence of similar local and widespread pressure hyperalgesia, not associated with anxiety or depression, in women with FETTH and CTTH supporting that localized and central manifestations are involved in both the episodic and chronic forms of tension-type headache. © 2016 American Headache Society.
Wang, Shuya; Liu, Kun; Wang, Yuan; Wang, Shuyou; He, Xun; Cui, Xiang; Gao, Xinyan; Zhu, Bing
2017-10-01
Objective: Scalp acupuncture is a somatic stimulation therapy that produces prominent clinical effects when used to treat cerebral diseases. However, this acupuncture's therapeutic mechanisms have not yet been well-addressed. Scalp acupoints are innervated by the trigeminal nerve, which is coincident with the intracranial sensory afferents as well as with the meningeal vessels. In recent years, cerebrospinal fluid-contacting neurons have been found and proved to transmit allergic substances between brain the parenchyma and meninges, representing a possible network between scalp acupuncture and the brain. The aim of the current study was to observe the connections between scalp acupoints and the meninges and to establish a possible mechanism for scalp acupuncture. Materials and Methods: Twenty-five adult Sprague-Dawley rats were used for the present study. Evans Blue dye (Sigma Chemical Co, St. Louis, MO) was injected though each rat's caudal vein after trigeminal stimulation for plasma extravasation observation. Cerebral blood flow (CBF) values of the rat's brain surface were measured at different timepoints before and after electroacupuncture (EA) on GB 15 ( Toulinqi ) or ST 36 ( Zusanli ). Results: These preliminary studies indicated that neurogenic plasma extravasation on a rat's skin and dura mater after mechanical or electrical stimulation of the trigeminal nerves is a reliable way to show the pathologic connection between scalp acupoints and the meninges. Moreover, CBF of the rat's brain surface is increased significantly after EA stimulation at GB 15 ( Toulinqi ), which is located in the receptive field of the supraorbital nerve. Conclusions: These findings suggest that the mechanism of scalp acupuncture might lie in the specific neurologic pathway that could be termed as trigeminal nerve-meninges-cerebrospinal fluid-contacting neurons-brain , which is a possible shortcut to brain functional regulation and cerebral disease treatment.
Anderson, C W
2001-09-01
Using injections of small molecular weight fluorescein dextran amines, combined with activity-dependent uptake of sulforhodamine 101 (SR101), brainstem circuits presumed to be involved in feeding motor output were investigated. As has been shown previously in other studies, projections to the cerebellar nuclei were identified from the cerebellar cortex, the trigeminal motor nucleus, and the vestibular nuclei. Results presented here suggest an additional pathway from the hypoglossal motor nuclei to the cerebellar nucleus as well as an afferent projection from the peripheral hypoglossal nerve to the Purkinje cell layer of the cerebellar cortex. Injections in the cerebellar cortex combined with retrograde labeling of the peripheral hypoglossal nerve demonstrate anatomical convergence at the level of the medial reticular formation. This suggests a possible integrative region for afferent feedback from the hypoglossal nerve and information through the Purkinje cell layer of the cerebellar cortex. The activity-dependent uptake of SR101 additionally suggests a reciprocal, polysynaptic pathway between this same area of the medial reticular formation and the trigeminal motor nuclei. The trigeminal motor neurons innervate the m adductor mandibulae, the primary mouth-closing muscle. The SR101 uptake clearly labeled the ventrolateral hypoglossal nuclei, the medial reticular formation, and the Purkinje cell layer of the cerebellar cortex. Unlike retrograde labeling of the peripheral hypoglossal nerve, stimulating the hypoglossal nerve while SR101 was bath-applied labeled trigeminal motor neurons. This, combined with the dextran labeling, suggests a reciprocal connection between the trigeminal motor nuclei and the cerebellar nuclei, as well as the medulla. Taken together, these data are important for understanding the neurophysiological pathways used to coordinate the proper timing of an extremely rapid, goal-directed movement and may prove useful for elucidating some of the first principles of sensorimotor integration.
Ferrari, Giulio; Chauhan, Sunil K; Ueno, Hiroki; Nallasamy, Nambi; Gandolfi, Stefano; Borges, Lawrence; Dana, Reza
2011-04-01
To develop a mouse model of neurotrophic keratopathy by approaching the trigeminal nerve through the brain and to evaluate changes in corneal cell apoptosis and proliferation. Six- to 8-week-old male C57BL/6 mice underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the procedure, we examined the gross nerve pathology, blink reflex, and immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67-positive proliferating corneal cells were evaluated to detect changes from the contralateral normal eye. TSE was confirmed by gross histology of the trigeminal nerve and was considered effective if the corneal blink reflex was completely abolished. TSE totally abolished the blink reflex in 70% of mice and significantly reduced it in the remaining 30%. Animals with absent blink reflex were used for subsequent experiments. In these mice, a progressive corneal degeneration developed, with thinning of the corneal epithelium and eventually perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were not recognizable histologically. Seven days after TSE, an increase in cellular apoptosis in all the corneal layers and a reduction in proliferation in basal epithelial cells were detected consistently in all mice. TSE was able, in most cases, to induce a disease state that reflected clinical neurotrophic keratitis without damaging the periocular structures. Moreover, corneal denervation led to increased apoptosis and reduced proliferation of epithelial cells, formally implicating intact nerve function in regulating epithelial survival and turnover.
Ferrari, Giulio; Chauhan, Sunil K.; Ueno, Hiroki; Nallasamy, Nambi; Gandolfi, Stefano; Borges, Lawrence
2011-01-01
Purpose. To develop a mouse model of neurotrophic keratopathy by approaching the trigeminal nerve through the brain and to evaluate changes in corneal cell apoptosis and proliferation. Methods. Six- to 8-week-old male C57BL/6 mice underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the procedure, we examined the gross nerve pathology, blink reflex, and immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67–positive proliferating corneal cells were evaluated to detect changes from the contralateral normal eye. Results. TSE was confirmed by gross histology of the trigeminal nerve and was considered effective if the corneal blink reflex was completely abolished. TSE totally abolished the blink reflex in 70% of mice and significantly reduced it in the remaining 30%. Animals with absent blink reflex were used for subsequent experiments. In these mice, a progressive corneal degeneration developed, with thinning of the corneal epithelium and eventually perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were not recognizable histologically. Seven days after TSE, an increase in cellular apoptosis in all the corneal layers and a reduction in proliferation in basal epithelial cells were detected consistently in all mice. Conclusions. TSE was able, in most cases, to induce a disease state that reflected clinical neurotrophic keratitis without damaging the periocular structures. Moreover, corneal denervation led to increased apoptosis and reduced proliferation of epithelial cells, formally implicating intact nerve function in regulating epithelial survival and turnover. PMID:21071731
Daiutolo, Brittany V.; Tyburski, Ashley; Clark, Shannon W.
2016-01-01
Abstract The pain-signaling molecules, nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic headache (PTH) as they are for migraine. This study assessed the changes of inducible NOS (iNOS) and its cellular source in the trigeminal pain circuit, as well as the relationship between iNOS and CGRP after controlled cortical impact (CCI) injury in mice. The effects of a CGRP antagonist (MK8825) and sumatriptan on iNOS messenger RNA (mRNA) and protein were compared to vehicle at 2 weeks postinjury. Changes in CGRP levels in the trigeminal nucleus caudalis (TNC) in iNOS knockouts with CCI were compared to wild-type (WT) mice at 3 days and 2 weeks post injury. Trigeminal allodynia and photosensitivity were measured. MK8825 and sumatriptan increased allodynic thresholds in CCI groups compared to vehicle (p < 0.01), whereas iNOS knockouts were not different from WT. Photosensitivity was attenuated in MK8825 mice and iNOS knockouts compared to WT (p < 0.05). MK8825 and sumatriptan reduced levels of iNOS mRNA and iNOS immunoreactivity in the TNC and ganglia (p < 0.01). Differences in iNOS cellular localization were found between the trigeminal ganglia and TNC. Although the knockout of iNOS attenuated CGRP at 3 days (p < 0.05), it did not reduce CGRP at 2 weeks. CGRP immunoreactivity was found in the meningeal layers post-CCI, while negligible in controls. Findings support the importance of interactions between CGRP and iNOS in mediating allodynia, as well as the individual roles in photosensitivity. Mitigating prolonged increases in CGRP may be a promising intervention for treating acute PTH. PMID:26472135
Pang, You-Wang; Ge, Shun-Nan; Nakamura, Kouichi C; Li, Jin-Lian; Xiong, Kang-Hui; Kaneko, Takeshi; Mizuno, Noboru
2009-02-10
Little is known about the significance of the two types of glutamatergic neurons (those expressing vesicular glutamate transporter VGLUT1 or VGLUT2) in the control of jaw movements. We thus examined the origin and distribution of axon terminals with VGLUT1 or VGLUT2 immunoreactivity within the trigeminal motor nucleus (Vm) in the rat. The Vm was divided into the dorsolateral division (Vm.dl; jaw-closing motoneuron pool) and the ventromedial division (Vm.vm; jaw-opening motoneuron pool). VGLUT1-immunopositive terminals were seen within the Vm.dl only, whereas VGLUT2-immunopositive ones were distributed to both the Vm.dl and the Vm.vm. Transection of the motor root eliminated almost all VGLUT1-immunopositive axons in the Vm.dl, with no changes of VGLUT2 immunoreactivity in the two divisions, indicating that the VGLUT1- and VGLUT2-immunopositive axons came from primary afferents in the mesencephalic trigeminal nucleus and premotor neurons for the Vm, respectively. In situ hybridization histochemistry revealed that VGLUT2 neurons were much more numerous than VGLUT1 neurons in the regions corresponding to the reported premotoneuron pool for the Vm. The results of immunofluorescence labeling combined with anterograde tract tracing further indicated that premotor neurons with VGLUT2 in the trigeminal sensory nuclei, the supratrigeminal region, and the reticular region ventral to the Vm sent axon terminals contacting trigeminal motoneurons and that some of the VGLUT1-expressing premotor neurons in the reticular region ventral to the Vm sent axon terminals to jaw-closing motoneurons. The present results suggested that the roles played by glutamatergic neurons in controlling jaw movements might be different between VGLUT1- and VGLUT2-expressing neurons.
[Microvascular descompression for trigeminal neuralgia: prognostic [corrected] factors].
Alberione, F; Arena, A; Matera, R
2008-06-01
We describe our experience of the MVD in the typical trigeminal neuralgia and identify the prognostic factors. A retrospective studio of 89 cases between 1995-2005 was used. The prognostic significant data evaluated were demographics data; duration of neuralgia; the affected divisions involved; surgical findings; used material for the decompression. The data analysis was made with the chi(2) test. We have found an excellent outcome in 77% one year later. The age and the antecedent of hypertension disease were not statistically significant. A poor outcome was observed for: female sex, neuralgia lasting longer than two years, the three divisions involved, venous compression and the muscle used as surgical material. The MVD is an effective and reliable technique. The use of muscle is not recommended. When the three trigeminal divisions are involved we should choose another technique.
Schwerdtner, O; Damaskos, T; Kage, A; Weitzel-Kage, D; Klein, M
2005-06-01
Trigeminal trophic syndrome is an extremely rare complication following surgical ablation of the trigeminal nerve or after alcohol injection or thermocoagulation of the Gasserian ganglion. These lesions show a poor healing tendency and sometimes persist for years. The therapeutic results of local wound care with ointments and wound dressings are often unsatisfactory, and those of plastic surgery are variable. In the case presented, the skin area affected by neurotrophic ulceration is successfully treated with autologous cultivated epidermal cells. This form of tissue engineering is already a clinically established procedure for treating burns and chronic wounds. The results show for the first time that transplantation of in vitro cultivated epidermal cells can induce tissue regeneration and may be an effective tool in the treatment of neurotrophic ulcerations in the facial region.
Unilateral nasal pain with migraine features.
Alvarez, Mónica; Montojo, Teresa; de la Casa, Beatriz; Vela, Lydia; Pareja, Juan A
2013-09-01
Migraine attacks exclusively felt in the face are very rare, the pain involving the territories supplied by the second and third branches of the trigeminal nerve. Two patients suffering from heminasal pain attacks accompanied with typical migrainous features and responsive to oral or intranasal triptans - but not to intranasal lidocaine or oxymetazoline. In one patient, the attacks could be precipitated upon slight touching on the tip of the nose, in the other attacks were preceded by the nasal sensation typically heralding sneezing. Migraine pain mostly develops within the innervation territory of the first branch of the trigeminal nerve, which includes the nose. Therefore, episodes of unilateral nasal pain with migrainous features could be considered a migraine with unusual topography (nasal migraine). Painful nasal attacks occasionally preceded by stimulation of trigeminal afferents in the nose, could be conceived of as migraine-tic syndrome.
Iannaccone, Francesco; Degroote, Joris; Vierendeels, Jan; Segers, Patrick
2016-01-01
In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations’ outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results. PMID:27128798
Sandberg, Troy E; Pedersen, Margit; LaCroix, Ryan A; Ebrahim, Ali; Bonde, Mads; Herrgard, Markus J; Palsson, Bernhard O; Sommer, Morten; Feist, Adam M
2014-10-01
Adaptive laboratory evolution (ALE) has emerged as a valuable method by which to investigate microbial adaptation to a desired environment. Here, we performed ALE to 42 °C of ten parallel populations of Escherichia coli K-12 MG1655 grown in glucose minimal media. Tightly controlled experimental conditions allowed selection based on exponential-phase growth rate, yielding strains that uniformly converged toward a similar phenotype along distinct genetic paths. Adapted strains possessed as few as 6 and as many as 55 mutations, and of the 144 genes that mutated in total, 14 arose independently across two or more strains. This mutational recurrence pointed to the key genetic targets underlying the evolved fitness increase. Genome engineering was used to introduce the novel ALE-acquired alleles in random combinations into the ancestral strain, and competition between these engineered strains reaffirmed the impact of the key mutations on the growth rate at 42 °C. Interestingly, most of the identified key gene targets differed significantly from those found in similar temperature adaptation studies, highlighting the sensitivity of genetic evolution to experimental conditions and ancestral genotype. Additionally, transcriptomic analysis of the ancestral and evolved strains revealed a general trend for restoration of the global expression state back toward preheat stressed levels. This restorative effect was previously documented following evolution to metabolic perturbations, and thus may represent a general feature of ALE experiments. The widespread evolved expression shifts were enabled by a comparatively scant number of regulatory mutations, providing a net fitness benefit but causing suboptimal expression levels for certain genes, such as those governing flagellar formation, which then became targets for additional ameliorating mutations. Overall, the results of this study provide insight into the adaptation process and yield lessons important for the future implementation of ALE as a tool for scientific research and engineering. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Multidirectional testing of one- and two-level ProDisc-L versus simulated fusions.
Panjabi, Manohar; Henderson, Gweneth; Abjornson, Celeste; Yue, James
2007-05-20
An in vitro human cadaveric biomechanical study. To evaluate intervertebral rotation changes due to lumbar ProDisc-L compared with simulated fusion, using follower load and multidirectional testing. Artificial discs, as opposed to the fusions, are thought to decrease the long-term accelerated degeneration at adjacent levels. A biomechanical assessment can be helpful, as the long-term clinical evaluation is impractical. Six fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension, bilateral lateral bending, and bilateral torsion using the Hybrid test method. First, intact specimen total range of rotation (T12-S1) was determined. Second, using pure moments again, this range of rotation was achieved in each of the 5 constructs: A) ProDisc-L at L5-S1; B) fusion at L5-S1; C) ProDisc-L at L4-L5 and fusion at L5-S1; D) ProDisc-L at L4-L5 and L5-S1; and E) 2-level fusion at L4-L5 to L5-S1. Significant changes in the intervertebral rotations due to each construct were determined at the operated and nonoperated levels using repeated measures single factor ANOVA and Bonferroni statistical tests (P < 0.05). Adjacent-level effects (ALEs) were defined as the percentage changes in intervertebral rotations at the nonoperated levels due to the constructs. One- and 2-level ProDisc-L constructs showed only small ALE in any of the 3 rotations. In contrast, 1- and 2-level fusions showed increased ALE in all 3 directions (average, 7.8% and 35.3%, respectively, for 1 and 2 levels). In the disc plus fusion combination (construct C), the ALEs were similar to the 1-level fusion alone. In general, ProDisc-L preserved physiologic motions at all spinal levels, while the fusion simulations resulted in significant ALE.
Hebestreit, Julia M; May, Arne
2017-12-19
Beta-blockers are a first choice migraine preventive medication. So far it is unknown how they exert their therapeutic effect in migraine. To this end we examined the neural effect of metoprolol on trigeminal pain processing in 19 migraine patients and 26 healthy controls. All participants underwent functional magnetic resonance imaging (fMRI) during trigeminal pain twice: Healthy subjects took part in a placebo-controlled, randomized and double-blind study, receiving a single dose of metoprolol and placebo. Patients were examined with a baseline scan before starting the preventive medication and 3 months later whilst treated with metoprolol. Mean pain intensity ratings were not significantly altered under metoprolol. Functional imaging revealed no significant differences in nociceptive processing in both groups. Contrary to earlier findings from animal studies, we did not find an effect of metoprolol on the thalamus in either group. However, using a more liberal and exploratory threshold, hypothalamic activity was slightly increased under metoprolol in patients and migraineurs. No significant effect of metoprolol on trigeminal pain processing was observed, suggesting a peripheral effect of metoprolol. Exploratory analyses revealed slightly enhanced hypothalamic activity under metoprolol in both groups. Given the emerging role of the hypothalamus in migraine attack generation, these data need further examination.
2014-01-01
Background Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing. Methods Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0–10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS. Results Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported. Conclusion Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment. PMID:25424567
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sekizawa, Shin-ichi, E-mail: ssekizawa@ucdavis.ed; Bechtold, Andrea G.; Tham, Rick C.
Allergic airway diseases in children are a common and a growing health problem. Changes in the central nervous system (CNS) have been implicated in contributing to some of the symptoms. We hypothesized that airway allergic diseases are associated with altered histamine H3 receptor expression in the nucleus tractus solitarius (NTS) and caudal spinal trigeminal nucleus, where lung/airway and nasal sensory afferents terminate, respectively. Immunohistochemistry for histamine H3 receptors was performed on brainstem sections containing the NTS and the caudal spinal trigeminal nucleus from 6- and 12-month-old rhesus monkeys who had been exposed for 5 months to house dust mite allergenmore » (HDMA) + O{sub 3} or to filtered air (FA). While histamine H3 receptors were found exclusively in astrocytes in the caudal spinal trigeminal nucleus, they were localized to both neuronal terminals and processes in the NTS. HDMA + O{sub 3} exposure significantly decreased histamine H3 receptor immunoreactivity in the NTS at 6 months and in the caudal spinal trigeminal nucleus at 12 months of age. In conclusion, exposing young primates to HDMA + O{sub 3} changed histamine H3 receptor expression in CNS pathways involving lung and nasal afferent nerves in an age-related manner. Histamine H3 receptors may be a therapeutic target for allergic asthma and rhinitis in children.« less
Stimulus Selection for Intranasal Sensory Isolation: Eugenol Is an Irritant
Wise, Paul M.; Lundström, Johan N.
2012-01-01
Both the olfactory and the trigeminal systems are able to respond to intranasal presentations of chemical vapor. Accordingly, when the nose detects a volatile chemical, it is often unclear whether we smell it, feel it, or both. The distinction may often be unimportant in our everyday perception of fragrances or aromas, but it can matter in experiments that purport to isolate olfactory processes or study the interaction between olfaction and chemesthesis. Researchers turn to a small pool of compounds that are believed to be “pure olfactory” stimuli with little or no trigeminal impact. The current report reexamines one such commonly used compound, namely eugenol, a flavor and fragrance ingredient that has anesthetic properties under some conditions. Using a standard method involving many trials during an experimental session (Experiment 1), subjects were unable to reliably lateralize eugenol, consistent with claims that this compound is detected primarily through olfaction. However, with more limited exposure (Experiments 2 and 3), subjects were able to lateralize eugenol. We speculate that anesthetic properties of eugenol could blunt its trigeminal impact in some paradigms. Regardless, the current experiments suggest that eugenol can in fact stimulate the trigeminal nerve but in a complex concentration–dependent manner. Implications and strategies for selection of model odorants are discussed. PMID:22293937
Kern, Kai-Uwe; Nalamachu, Srinivas; Brasseur, Louis; Zakrzewska, Joanna M
2013-01-01
An expert group of 40 pain specialists from 16 countries performed a first assessment of the value of predictors for treatment success with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain. Results were based on the retrospective analysis of 68 case reports (sent in by participants in the 4 weeks prior to the conference) and the practical experience of the experts. Lidocaine plaster treatment was mostly successful for surgery or chemotherapy-related cancer pain with neuropathic components. A dose reduction of systemic pain treatment was observed in at least 50% of all cancer pain patients using the plaster as adjunct treatment; the presence of allodynia, hyperalgesia or pain quality provided a potential but not definitively clear indication of treatment success. In trigeminal neuropathic pain, continuous pain, severe allodynia, hyperalgesia, or postherpetic neuralgia or trauma as the cause of orofacial neuropathic pain were perceived as potential predictors of treatment success with lidocaine plaster. In conclusion, these findings provide a first assessment of the likelihood of treatment benefits with 5% lidocaine-medicated plaster in the management of cancer pain with neuropathic components and trigeminal neuropathic pain and support conducting large, well-designed multicenter studies. PMID:23630431
Cytoarchitectonic study of the trigeminal ganglion in humans.
Krastev, Dimo Stoyanov; Apostolov, Alexander
2013-01-01
The trigeminal ganglion (TG), a cluster of pseudounipolar neurons, is located in the trigeminal impression of the temporal pyramid. It is covered by a sheath of the dura mater and arachnoid and is near the rear end of the cavernous sinus. The peripheral processes of the pseudounipolar cells are involved in the formation of the first and second branch and the sensory part of the third branch of the fifth cranial nerve, and the central ones form the sensory root of the nerve, which penetrates at the level of the middle cerebellar peduncle, aside from the pons, and terminate in the sensory nuclei of the trigeminal complex. We found that the primary sensory neurons involved in sensory innervation of the orofacial complex are a diverse group. Although they possess the general structure of pseudounipolar neurons, there are significant differences among them, seen in varying intensities of staining. Based on our investigations we classified the neurons into 7 groups, i.e. large, subdivided into light and dark, medium, also light and dark, and small light and dark, and, moreover, neurons with an irregular shape of their perikarya. Further research by applying various immunohistochemical methods will clarify whether differences in the morphological patterns of the neurons are associated with differences in the neurochemical composition of various neuronal types.
Cytoarchitectonic study of the trigeminal ganglion in humans
KRASTEV, DIMO STOYANOV; APOSTOLOV, ALEXANDER
2013-01-01
The trigeminal ganglion (TG), a cluster of pseudounipolar neurons, is located in the trigeminal impression of the temporal pyramid. It is covered by a sheath of the dura mater and arachnoid and is near the rear end of the cavernous sinus. The peripheral processes of the pseudounipolar cells are involved in the formation of the first and second branch and the sensory part of the third branch of the fifth cranial nerve, and the central ones form the sensory root of the nerve, which penetrates at the level of the middle cerebellar peduncle, aside from the pons, and terminate in the sensory nuclei of the trigeminal complex. We found that the primary sensory neurons involved in sensory innervation of the orofacial complex are a diverse group. Although they possess the general structure of pseudounipolar neurons, there are significant differences among them, seen in varying intensities of staining. Based on our investigations we classified the neurons into 7 groups, i.e. large, subdivided into light and dark, medium, also light and dark, and small light and dark, and, moreover, neurons with an irregular shape of their perikarya. Further research by applying various immunohistochemical methods will clarify whether differences in the morphological patterns of the neurons are associated with differences in the neurochemical composition of various neuronal types. PMID:26527926
Synthetic Neurotensin Analogues Are Nontoxic Analgesics for the Rabbit Cornea
Kim, Charles; Barbut, Denise; Heinemann, Murk H.; Pasternak, Gavril; Rosenblatt, Mark I.
2014-01-01
Purpose. To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Methods. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. Results. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Conclusions. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. PMID:24825106
Tramonti Fantozzi, Maria Paola; De Cicco, Vincenzo; Barresi, Massimo; Cataldo, Enrico; Faraguna, Ugo; Bruschini, Luca; Manzoni, Diego
2017-01-01
Trigeminal input to the ascending activating system is important for the maintenance of arousal and may affect the discharge of the noradrenergic neurons of the locus coeruleus (LC), whose activity influences both vigilance state and pupil size, inducing mydriasis. For this reason, pupil size evaluation is now considered an indicator of LC activity. Since mastication activates trigeminal afferent neurons, the aims of the present study, conducted on healthy adult participants, were to investigate whether chewing a bolus of different hardness may: (1) differentially affect the performance on a cognitive task (consisting in the retrieval of specific target numbers within numerical matrices) and (2) increase the dilatation of the pupil (mydriasis) induced by a haptic task, suggesting a change in LC activation. Results show that chewing significantly increased both the velocity of number retrieval (without affecting the number of errors) and the mydriasis associated with the haptic task, whereas simple task repetition did not modify either retrieval or mydriasis. Handgrip exercise, instead, significantly decreased both parameters. Effects were significantly stronger and longer lasting when subjects chewed hard pellets. Finally, chewing-induced improvements in performance and changes in mydriasis were positively correlated, which suggests that trigeminal signals enhanced by chewing may boost the cognitive performance by increasing LC activity. PMID:28848404
Dalewski, B; Chruściel-Nogalska, M; Frączak, B
2015-12-01
An occlusal splint and a modified nociceptive trigeminal inhibition splint (AMPS, anterior deprogrammer, Kois deprogrammer, Lucia jig, etc.) are commonly and quite frequently used in the treatment of masticatory muscle disorders, although their sustainable and long-lasting effect on these muscles' function is still not very well known. Results of scant surface electromyography studies in patients with temporomandibular disorders have been contradictory. The aim of this study was to evaluate both devices in bruxism therapy; EMG activity levels during postural activity and maximum voluntary contraction of the superficial temporal and masseter muscles were compared before and after 30 days of treatment. Surface electromyography of the examined muscles was performed in two groups of bruxers (15 patients each). Patients in the first group used occlusal splints, while those in the second used modified nociceptive trigeminal inhibition splints. The trial was randomized, controlled and semi-blind. Neither device affected the asymmetry index or postural activity/maximum voluntary contraction ratio after 1 month of treatment. Neither the occlusal nor the nociceptive trigeminal inhibition splint showed any significant influence on the examined muscles. Different scientific methods should be considered in clinical applications that require either direct influence on the muscles' bioelectrical activity or a quantitative measurement of the treatment quality. © 2015 Australian Dental Association.
Macrini, Thomas E; Rowe, Timothy; Archer, Michael
2006-08-01
A digital cranial endocast of the Miocene platypus Obdurodon dicksoni was extracted from high-resolution X-ray computed tomography scans. This endocast represents the oldest from an unequivocal member of either extant monotreme lineage and is therefore important for inferring character support for Monotremata, a clade that is not well diagnosed. We describe the Obdurodon endocast with reference to endocasts extracted from skulls of the three species of extant monotremes, particularly Ornithorhynchus anatinus, the duckbill platypus. We consulted published descriptions and illustrations of whole and sectioned brains of monotremes to determine which external features of the nervous system are represented on the endocasts. Similar to Ornithorhynchus, well-developed parafloccular casts and reduced olfactory bulb casts are present in the Obdurodon endocast. Reduction of the olfactory bulbs in comparison with tachyglossids and therian mammals is a potential apomorphy for Ornithorhynchidae. The trigeminal nuclei, ganglia, and nerves (i.e., trigeminal complex) are enlarged in Obdurodon, as evidenced by their casts on the endocast, as is the case in the extant platypus. The visibility of enlarged trigeminal nucleus casts on the endocasts of Obdurodon and Ornithorhynchus is a possible synapomorphy of Ornithorhynchidae. Electroreception and enlargement of the trigeminal complex are possible synapomorphies for Monotremata. Copyright 2006 Wiley-Liss, Inc.
New Insights in Trigeminal Anatomy: A Double Orofacial Tract for Nociceptive Input
Henssen, Dylan J. H. A.; Kurt, Erkan; Kozicz, Tamas; van Dongen, Robert; Bartels, Ronald H. M. A.; van Cappellen van Walsum, Anne-Marie
2016-01-01
Orofacial pain in patients relies on the anatomical pathways that conduct nociceptive information, originating from the periphery towards the trigeminal sensory nucleus complex (TSNC) and finally, to the thalami and the somatosensorical cortical regions. The anatomy and function of the so-called trigeminothalamic tracts have been investigated before. In these animal-based studies from the previous century, the intracerebral pathways were mapped using different retro- and anterograde tracing methods. We review the literature on the trigeminothalamic tracts focusing on these animal tracer studies. Subsequently, we related the observations of these studies to clinical findings using fMRI trials. The intracerebral trigeminal pathways can be subdivided into three pathways: a ventral (contralateral) and dorsal (mainly ipsilateral) trigeminothalamic tract and the intranuclear pathway. Based on the reviewed evidence we hypothesize the co-existence of an ipsilateral nociceptive conduction tract to the cerebral cortex and we translate evidence from animal-based research to the human anatomy. Our hypothesis differs from the classical idea that orofacial pain arises only from nociceptive information via the contralateral, ventral trigeminothalamic pathway. Better understanding of the histology, anatomy and connectivity of the trigeminal fibers could contribute to the discovery of a more effective pain treatment in patients suffering from various orofacial pain syndromes. PMID:27242449
Iatrogenic trigeminal post-traumatic neuropathy: a retrospective two-year cohort study.
Klazen, Y; Van der Cruyssen, F; Vranckx, M; Van Vlierberghe, M; Politis, C; Renton, T; Jacobs, R
2018-06-01
With the growing demand for dental work, trigeminal nerve injuries are increasingly common. This retrospective cohort study examined 53 cases of iatrogenic trigeminal nerve injury seen at the Department of Oral and Maxillofacial Surgery, University Hospitals of Leuven between 2013 and 2014 (0.6% among 8845 new patient visits). Patient records were screened for post-traumatic trigeminal nerve neuropathy caused by nerve injury incurred during implant surgery, endodontic treatment, local anaesthesia, tooth extraction, or specifically third molar removal. The patients ranged in age from 15 to 80years (mean age 42.1years) and 68% were female. The referral delay ranged from 1day to 6.5years (average 10months). The inferior alveolar nerve (IAN) was most frequently injured (28 cases), followed by the lingual nerve (LN) (21 cases). Most nerve injuries were caused during third molar removal (24 cases), followed by implant placement (nine cases) and local anaesthesia injuries (nine cases). Pain symptoms were experienced by 54% of patients suffering IAN injury, compared to 10% of patients with LN injury. Persistent neurosensory disturbances were identified in 60% of patients. While prevention remains the key issue, timely referral seems to be a critical factor for the successful treatment of post-traumatic neuropathy. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Atmospheric emissions and trends of nitrous oxide deduced from 10 years of ALE-GAGE data
NASA Technical Reports Server (NTRS)
Prinn, R.; Cunnold, D.; Alyea, F.; Rasmussen, R.; Simmonds, P.
1990-01-01
Long-term measurements of nitrous oxide (N2O) obtained during the Atmospheric Lifetime Experiment (ALE) and the Global Atmospheric Gases Experiment (GAGE) for a period from 1978 to 1988 are presented and interpreted. It is observed that the average concentration in the Northern Hemisphere is 0.75 +/- 0.16 ppbv higher than in the Southern Hemisphere and that the global average linear trend in N2O lies in the range from 0.25 to 0.31 percent/year. The measured trends and latitudinal distributions are shown to be consistent with the hypothesis that stratospheric photodissociation is the major atmospheric sink for N2O, while the cause of the N2O trend is suggested to be a combination of a growing tropical source and a growing Northern mid-latitude source. A 10-year average global N2O emission rate of (20.5 +/- 2.4) x 10 to the 12th g N2O/year is deduced from the ALE/GAGE data.
Toward Improved Fidelity of Thermal Explosion Simulations
NASA Astrophysics Data System (ADS)
Nichols, Albert; Becker, Richard; Burnham, Alan; Howard, W. Michael; Knap, Jarek; Wemhoff, Aaron
2009-06-01
We present results of an improved thermal/chemical/mechanical model of HMX based explosives like LX04 and LX10 for thermal cook-off. The original HMX model and analysis scheme were developed by Yoh et.al. for use in the ALE3D modeling framework. The improvements were concentrated in four areas. First, we added porosity to the chemical material model framework in ALE3D used to model HMX explosive formulations to handle the roughly 2% porosity in solid explosives. Second, we improved the HMX reaction network, which included the addition of a reactive phase change model base on work by Henson et.al. Third, we added early decomposition gas species to the CHEETAH material database to improve equations of state for gaseous intermediates and products. Finally, we improved the implicit mechanics module in ALE3D to more naturally handle the long time scales associated with thermal cookoff. The application of the resulting framework to the analysis of the Scaled Thermal Explosion (STEX) experiments will be discussed.
NASA Astrophysics Data System (ADS)
Melis, Matthew E.
2003-01-01
Explicit finite element techniques employing an Arbitrary Lagrangian-Eulerian (ALE) methodology, within the transient dynamic code LS-DYNA, are used to predict splashdown loads on a proposed replacement/upgrade of the hydrazine tanks on the thrust vector control system housed within the aft skirt of a Space Shuttle Solid Rocket Booster. Two preliminary studies are performed prior to the full aft skirt analysis: An analysis of the proposed tank impacting water without supporting aft skirt structure, and an analysis of space capsule water drop tests conducted at NASA's Langley Research Center. Results from the preliminary studies provide confidence that useful predictions can be made by applying the ALE methodology to a detailed analysis of a 26-degree section of the skirt with proposed tank attached. Results for all three studies are presented and compared to limited experimental data. The challenges of using the LS-DYNA ALE capability for this type of analysis are discussed.
New frontiers of atomic layer etching
NASA Astrophysics Data System (ADS)
Sherpa, Sonam D.; Ranjan, Alok
2018-03-01
Interest in atomic layer etching (ALE) has surged recently because it offers several advantages over continuous or quasicontinuous plasma etching. These benefits include (1) independent control of ion energy, ion flux, and radical flux, (2) flux-independent etch rate that mitigates the iso-dense loading effects, and (3) ability to control the etch rate with atomic or nanoscale precision. In addition to these benefits, we demonstrate an area-selective etching for maskless lithography as a new frontier of ALE. In this paper, area-selective etching refers to the confinement of etching into the specific areas of the substrate. The concept of area-selective etching originated during our studies on quasi-ALE of silicon nitride which consists of sequential exposure of silicon nitride to hydrogen and fluorinated plasma. The findings of our studies reported in this paper suggest that it may be possible to confine the etching into specific areas of silicon nitride without using any mask by replacing conventional hydrogen plasma with a localized source of hydrogen ions.
Chao, Chun-Tang
2014-01-01
This paper presents the design and evaluation of the hardware circuit for electronic stethoscopes with heart sound cancellation capabilities using field programmable gate arrays (FPGAs). The adaptive line enhancer (ALE) was adopted as the filtering methodology to reduce heart sound attributes from the breath sounds obtained via the electronic stethoscope pickup. FPGAs were utilized to implement the ALE functions in hardware to achieve near real-time breath sound processing. We believe that such an implementation is unprecedented and crucial toward a truly useful, standalone medical device in outpatient clinic settings. The implementation evaluation with one Altera cyclone II–EP2C70F89 shows that the proposed ALE used 45% resources of the chip. Experiments with the proposed prototype were made using DE2-70 emulation board with recorded body signals obtained from online medical archives. Clear suppressions were observed in our experiments from both the frequency domain and time domain perspectives. PMID:24790573
NASA Technical Reports Server (NTRS)
Melis, Matthew E.
2003-01-01
Explicit finite element techniques employing an Arbitrary Lagrangian-Eulerian (ALE) methodology, within the transient dynamic code LS-DYNA, are used to predict splashdown loads on a proposed replacement/upgrade of the hydrazine tanks on the thrust vector control system housed within the aft skirt of a Space Shuttle Solid Rocket Booster. Two preliminary studies are performed prior to the full aft skirt analysis: An analysis of the proposed tank impacting water without supporting aft skirt structure, and an analysis of space capsule water drop tests conducted at NASA's Langley Research Center. Results from the preliminary studies provide confidence that useful predictions can be made by applying the ALE methodology to a detailed analysis of a 26-degree section of the skirt with proposed tank attached. Results for all three studies are presented and compared to limited experimental data. The challenges of using the LS-DYNA ALE capability for this type of analysis are discussed.
Deployment Simulation Methods for Ultra-Lightweight Inflatable Structures
NASA Technical Reports Server (NTRS)
Wang, John T.; Johnson, Arthur R.
2003-01-01
Two dynamic inflation simulation methods are employed for modeling the deployment of folded thin-membrane tubes. The simulations are necessary because ground tests include gravity effects and may poorly represent deployment in space. The two simulation methods are referred to as the Control Volume (CV) method and the Arbitrary Lagrangian Eulerian (ALE) method. They are available in the LS-DYNA nonlinear dynamic finite element code. Both methods are suitable for modeling the interactions between the inflation gas and the thin-membrane tube structures. The CV method only considers the pressure induced by the inflation gas in the simulation, while the ALE method models the actual flow of the inflation gas. Thus, the transient fluid properties at any location within the tube can be predicted by the ALE method. Deployment simulations of three packaged tube models; namely coiled, Z-folded, and telescopically-folded configurations, are performed. Results predicted by both methods for the telescopically-folded configuration are correlated and computational efficiency issues are discussed.
[Occipital neuralgia with visual obscurations: a case report].
Selekler, Hamit Macit; Dündar, Gülmine; Kutlu, Ayşe
2010-07-01
Vertigo, dizziness and visual blurring have been reported in painful conditions in trigeminal innervation zones such as in idiopathic stabbing headache, supraorbital neuralgia or trigeminal nerve ophthalmic branch neuralgia. Although not common, pain in occipital neuralgia can spread through the anterior parts of the head. In this article, we present a case whose occipital neuralgiform paroxysms spread to the ipsilateral eye with simultaneous visual obscuration; the mechanisms of propagation and visual obscuration are discussed.
Diamond, S; Freitag, F G; Cohen, J S
1984-02-01
Cluster headache and trigeminal neuralgia (tic douloureux) share a common pattern of exacerbation and remission of pain that is described in similar terms by patients. Although the treatment of these conditions is markedly different, the results of adequate prophylaxis can be extremely impressive in both. The physician who treats headache patients should be aware of the common characteristics of each condition and of the possibility of their concomitant occurrence.
[Muscle relaxants in the treatment of idiopathic trigeminal neuralgia (author's transl)].
von Albert, H H
1975-08-29
In 195 patients with idiopathic trigeminal neuralgias, atypical facial neuralgia or zoster neuralgia in the face it was shown that, in the initial stages of these diseases, the efficacy of the always satisfactory medicinal treatment with an anticonvulsant (hydantoin or carbamezathine) can be increased by combination with a muscle relaxant (especially chlormezanone). Medicinal therapy is then still frequently possible without side effects and operative treatment (Frazier-Spiller's retrogasserian neurotomy) can be postponed.
Intracranial Management of Perineural Spread in the Trigeminal Nerve.
Redmond, Michael J; Panizza, Benedict J
2016-04-01
Since the mid-1960s surgeons have attempted to cure intracranial perineural spread (PNS) of cutaneous malignancies. Untreated patients with trigeminal PNS die from brainstem invasion and leptomeningeal disease. It was understood that resection with clear margins was potentially curative, but early surgical attempts were unsuccessful. The prevailing wisdom considered that this surgery failed to improve the results achieved with radiation therapy alone and was associated with high morbidity. However, with improved imaging, surgical equipment, and better understanding of cavernous sinus (CS) anatomy and access, contemporary surgeons can improve outcomes for this disease. The aim of this paper is to describe a technique to access the interdural compartment of the CS and treat PNS of cutaneous squamous cell carcinoma (cSCC) in the intracranial trigeminal nerve and ganglion. It is based on the experience of the Queensland Skull Base Unit, Australia in managing PNS of cutaneous squamous cell carcinoma of the head and neck (cSCCHN).
Post-traumatic external nasal pain syndrome (a trigeminal based pain disorder).
Rozen, Todd
2009-09-01
Little has been written about persistent external nasal pain after injury to the nose in the neurologic or headache literature. In clinical practice, this can be a disabling and treatment refractory condition. The external portion of the nose is highly innervated by branches of the ophthalmic and maxillary divisions of the trigeminal nerve including the nasociliary nerve, external nasal nerve, infratrochlear nerve, anterior ethmoidal nerve, and infraorbital nerve. As these nerves are located on the external portion of the nose just deep enough to the skin they can be easily traumatized with any impact to the nose. Four patients with what is termed the post-traumatic external nasal pain syndrome are reported in this paper, describing the clinical presentation of the disorder and providing treatment options. Post-traumatic external nasal pain syndrome appears to be a novel form of trigeminal-based pain not previously reported in the neurologic literature.
Hassan, Samih; Lagrata, Susie; Levy, Andrew; Matharu, Manjit; Zrinzo, Ludvic
2018-02-01
Objectives To assess the effectiveness of neuromodulation and trigeminal microvascular decompression (MVD) in patients with medically-intractable short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). Methods Two patients with medically refractory SUNCT underwent MVD following beneficial but incomplete response to neuromodulation (occipital nerve stimulation and deep brain stimulation). MRI confirmed neurovascular conflict with the ipsilateral trigeminal nerve in both patients. Results Although neuromodulation provided significant benefit, it did not deliver complete relief from pain and management required numerous postoperative visits with adjustment of medication and stimulation parameters. Conversely, MVD was successful in eliminating symptoms of SUNCT in both patients with no need for further medical treatment or neuromodulation. Conclusion Neuromodulation requires expensive hardware and lifelong follow-up and maintenance. These case reports highlight that microvascular decompression may be preferable to neuromodulation in the subset of SUNCT patients with ipsilateral neurovascular conflict.
Electrophysiology of Cranial Nerve Testing: Trigeminal and Facial Nerves.
Muzyka, Iryna M; Estephan, Bachir
2018-01-01
The clinical examination of the trigeminal and facial nerves provides significant diagnostic value, especially in the localization of lesions in disorders affecting the central and/or peripheral nervous system. The electrodiagnostic evaluation of these nerves and their pathways adds further accuracy and reliability to the diagnostic investigation and the localization process, especially when different testing methods are combined based on the clinical presentation and the electrophysiological findings. The diagnostic uniqueness of the trigeminal and facial nerves is their connectivity and their coparticipation in reflexes commonly used in clinical practice, namely the blink and corneal reflexes. The other reflexes used in the diagnostic process and lesion localization are very nerve specific and add more diagnostic yield to the workup of certain disorders of the nervous system. This article provides a review of commonly used electrodiagnostic studies and techniques in the evaluation and lesion localization of cranial nerves V and VII.
The biology of herpes simplex virus infection in humans.
Baringer, J R
1976-01-01
Herpes simplex virus is a frequent cause of recurrent ocular, oral, genital or cutaneous eruptions in man. Lesions are highly localized and tend to recur at the same site. Among the most consistent factors provoking recurrence is root section of the trigeminal nerve. Clinical and experimental data suggest that herpes simplex virus is commonly resident within the trigeminal ganglia of man, where it may be responsible for recurrent oral or lip lesions, and is less frequently a resident of the second or third sacral ganglia where it might be responsible for genital eruptions. Generally, the trigeminal virus is type 1 and the sacral virus is type 2; the virus is only rarely recoverable from other sensory ganglia. Factors provoking the reactivation from the virus' latent site and the mechanism for reactivation remain largely unknown. Further study is needed to understand the behavior of HSV and other viruses in nervous system tissue.
2010-01-01
Background Pain due to temporomandibular disorders (TMDs) often has the same clinical symptoms and signs as other types of orofacial pain (OP). The possible presence of serious neurological and/or systemic organic pathologies makes differential diagnosis difficult, especially in early disease stages. In the present study, we performed a qualitative and quantitative electrophysiological evaluation of the neuromuscular responses of the trigeminal nervous system. Using the jaw jerk reflex (JJ) and the motor evoked potentials of the trigeminal roots (bR-MEPs) tests, we investigated the functional and organic responses of healthy subjects (control group) and patients with TMD symptoms (TMD group). Method Thirty-three patients with temporomandibular disorder (TMD) symptoms and 36 control subjects underwent two electromyographic (EMG) tests: the jaw jerk reflex test and the motor evoked potentials of the trigeminal roots test using bilateral electrical transcranial stimulation. The mean, standard deviation, median, minimum, and maximum values were computed for the EMG absolute values. The ratio between the EMG values obtained on each side was always computed with the reference side as the numerator. For the TMD group, this side was identified as the painful side (pain side), while for the control group this was taken as the non-preferred masticatory side (non-preferred side). The 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were also calculated. Results Analysis of the ratios (expressed as percentages) between the values obtained on both sides revealed a high degree of symmetry in the bR-MEPs % in the control (0.93 ± 0.12%) and TMD (0.91 ± 0.22%) groups. This symmetry indicated organic integrity of the trigeminal root motor fibers and correct electrode arrangement. A degree of asymmetry of the jaw jerk's amplitude between sides (ipJJ%), when the mandible was kept in the intercuspal position, was found in the TMD group (0.24% ± 0.14%) with a statistically significant difference in relation to the control group (0.61% ± 0.2%). This asymmetry seemed to be primarily due to a failure to facilitate the reflex on the painful side in intercuspal position. Conclusions In this 2 × 2 matrix diagnostic model, three different types of headache may be identified: 1) those due to organic pathologies directly and indirectly involving the trigeminal nervous system denoted as "Organic Damage"; 2) those in TMD patients; 3) other types of orofacial pain in subjects who could erroneously be considered healthy, denoted as Orofacial Pain "OP". This category of patient should be considered at risk, as organic neurological pathologies could be present and yet not directly affect the trigeminal system, at least in the early stages of the disease. PMID:20594304
Guclu, Bulent; Sindou, Marc; Meyronet, David; Streichenberger, Nathalie; Simon, Emile; Mertens, Patrick
2011-12-01
The aim of this study was to evaluate the anatomy of the central myelin portion and the central myelin-peripheral myelin transitional zone of the trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The aim was also to investigate the relationship between the length and volume of the central myelin portion of these nerves with the incidences of the corresponding cranial dysfunctional syndromes caused by their compression to provide some more insights for a better understanding of mechanisms. The trigeminal, facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined. The length of these nerves from the brainstem to the foramen that they exit were measured. Longitudinal sections were stained and photographed to make measurements. The diameters of the nerves where they exit/enter from/to brainstem, the diameters where the transitional zone begins, the distances to the most distal part of transitional zone from brainstem and depths of the transitional zones were measured. Most importantly, the volume of the central myelin portion of the nerves was calculated. Correlation between length and volume of the central myelin portion of these nerves and the incidences of the corresponding hyperactive dysfunctional syndromes as reported in the literature were studied. The distance of the most distal part of the transitional zone from the brainstem was 4.19 ± 0.81 mm for the trigeminal nerve, 2.86 ± 1.19 mm for the facial nerve, 1.51 ± 0.39 mm for the glossopharyngeal nerve, and 1.63 ± 1.15 mm for the vagus nerve. The volume of central myelin portion was 24.54 ± 9.82 mm(3) in trigeminal nerve; 4.43 ± 2.55 mm(3) in facial nerve; 1.55 ± 1.08 mm(3) in glossopharyngeal nerve; 2.56 ± 1.32 mm(3) in vagus nerve. Correlations (p < 0.001) have been found between the length or volume of central myelin portions of the trigeminal, facial, glossopharyngeal and vagus nerves and incidences of the corresponding diseases. At present it is rather well-established that primary trigeminal neuralgia, hemifacial spasm and vago-glossopharyngeal neuralgia have as one of the main causes a vascular compression. The strong correlations found between the lengths and volumes of the central myelin portions of the nerves and the incidences of the corresponding diseases is a plea for the role played by this anatomical region in the mechanism of these diseases.
Burton, Donald E.; Morgan, Nathaniel Ray; Charest, Marc Robert Joseph; ...
2017-11-22
From the very origins of numerical hydrodynamics in the Lagrangian work of von Neumann and Richtmyer [83], the issue of total energy conservation as well as entropy production has been problematic. Because of well known problems with mesh deformation, Lagrangian schemes have evolved into Arbitrary Lagrangian–Eulerian (ALE) methods [39] that combine the best properties of Lagrangian and Eulerian methods. Energy issues have persisted for this class of methods. We believe that fundamental issues of energy conservation and entropy production in ALE require further examination. The context of the paper is an ALE scheme that is extended in the sense thatmore » it permits cyclic or periodic remap of data between grids of the same or differing connectivity. The principal design goals for a remap method then consist of total energy conservation, bounded internal energy, and compatibility of kinetic energy and momentum. We also have secondary objectives of limiting velocity and stress in a non-directional manner, keeping primitive variables monotone, and providing a higher than second order reconstruction of remapped variables. Particularly, the new contributions fall into three categories associated with: energy conservation and entropy production, reconstruction and bounds preservation of scalar and tensor fields, and conservative remap of nonlinear fields. Our paper presents a derivation of the methods, details of implementation, and numerical results for a number of test problems. The methods requires volume integration of polynomial functions in polytopal cells with planar facets, and the requisite expressions are derived for arbitrary order.« less
NASA Astrophysics Data System (ADS)
Xu, Wenbin; Rivalta, Eleonora; Li, Xing
2017-10-01
Understanding the magmatic systems beneath rift volcanoes provides insights into the deeper processes associated with rift architecture and development. At the slow spreading Erta Ale segment (Afar, Ethiopia) transition from continental rifting to seafloor spreading is ongoing on land. A lava lake has been documented since the twentieth century at the summit of the Erta Ale volcano and acts as an indicator of the pressure of its magma reservoir. However, the structure of the plumbing system of the volcano feeding such persistent active lava lake and the mechanisms controlling the architecture of magma storage remain unclear. Here, we combine high-resolution satellite optical imagery and radar interferometry (InSAR) to infer the shape, location and orientation of the conduits feeding the 2017 Erta Ale eruption. We show that the lava lake was rooted in a vertical dike-shaped reservoir that had been inflating prior to the eruption. The magma was subsequently transferred into a shallower feeder dike. We also find a shallow, horizontal magma lens elongated along axis inflating beneath the volcano during the later period of the eruption. Edifice stress modeling suggests the hydraulically connected system of horizontal and vertical thin magmatic bodies able to open and close are arranged spatially according to stresses induced by loading and unloading due to topographic changes. Our combined approach may provide new constraints on the organization of magma plumbing systems beneath volcanoes in continental and marine settings.
NASA Astrophysics Data System (ADS)
Burton, D. E.; Morgan, N. R.; Charest, M. R. J.; Kenamond, M. A.; Fung, J.
2018-02-01
From the very origins of numerical hydrodynamics in the Lagrangian work of von Neumann and Richtmyer [83], the issue of total energy conservation as well as entropy production has been problematic. Because of well known problems with mesh deformation, Lagrangian schemes have evolved into Arbitrary Lagrangian-Eulerian (ALE) methods [39] that combine the best properties of Lagrangian and Eulerian methods. Energy issues have persisted for this class of methods. We believe that fundamental issues of energy conservation and entropy production in ALE require further examination. The context of the paper is an ALE scheme that is extended in the sense that it permits cyclic or periodic remap of data between grids of the same or differing connectivity. The principal design goals for a remap method then consist of total energy conservation, bounded internal energy, and compatibility of kinetic energy and momentum. We also have secondary objectives of limiting velocity and stress in a non-directional manner, keeping primitive variables monotone, and providing a higher than second order reconstruction of remapped variables. In particular, the new contributions fall into three categories associated with: energy conservation and entropy production, reconstruction and bounds preservation of scalar and tensor fields, and conservative remap of nonlinear fields. The paper presents a derivation of the methods, details of implementation, and numerical results for a number of test problems. The methods requires volume integration of polynomial functions in polytopal cells with planar facets, and the requisite expressions are derived for arbitrary order.
Miyata, T; van Ypersele de Strihou, C; Kurokawa, K; Baynes, J W
1999-02-01
Advanced glycation end products (AGEs), formed during Maillard or browning reactions by nonenzymatic glycation and oxidation (glycoxidation) of proteins, have been implicated in the pathogenesis of several diseases, including diabetes and uremia. AGEs, such as pentosidine and carboxymethyllysine, are markedly elevated in both plasma proteins and skin collagen of uremic patients, irrespective of the presence of diabetes. The increased chemical modification of proteins is not limited to AGEs, because increased levels of advanced lipoxidation end products (ALEs), such as malondialdehydelysine, are also detected in plasma proteins in uremia. The accumulation of AGEs and ALEs in uremic plasma proteins is not correlated with increased blood glucose or triglycerides, nor is it determined by a decreased removal of chemically modified proteins by glomerular filtration. It more likely results from increased plasma concentrations of small, reactive carbonyl precursors of AGEs and ALEs, such as glyoxal, methylglyoxal, 3-deoxyglucosone, dehydroascorbate, and malondialdehyde. Thus, uremia may be described as a state of carbonyl overload or "carbonyl stress" resulting from either increased oxidation of carbohydrates and lipids (oxidative stress) or inadequate detoxification or inactivation of reactive carbonyl compounds derived from both carbohydrates and lipids by oxidative and nonoxidative chemistry. Carbonyl stress in uremia may contribute to the long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis and accelerated atherosclerosis. The increased levels of AGEs and ALEs in uremic blood and tissue proteins suggest a broad derangement in the nonenzymatic biochemistry of both carbohydrates and lipids.
NASA Astrophysics Data System (ADS)
Ren, Xiaodong; Xu, Kun; Shyy, Wei
2016-07-01
This paper presents a multi-dimensional high-order discontinuous Galerkin (DG) method in an arbitrary Lagrangian-Eulerian (ALE) formulation to simulate flows over variable domains with moving and deforming meshes. It is an extension of the gas-kinetic DG method proposed by the authors for static domains (X. Ren et al., 2015 [22]). A moving mesh gas kinetic DG method is proposed for both inviscid and viscous flow computations. A flux integration method across a translating and deforming cell interface has been constructed. Differently from the previous ALE-type gas kinetic method with piecewise constant mesh velocity at each cell interface within each time step, the mesh velocity variation inside a cell and the mesh moving and rotating at a cell interface have been accounted for in the finite element framework. As a result, the current scheme is applicable for any kind of mesh movement, such as translation, rotation, and deformation. The accuracy and robustness of the scheme have been improved significantly in the oscillating airfoil calculations. All computations are conducted in a physical domain rather than in a reference domain, and the basis functions move with the grid movement. Therefore, the numerical scheme can preserve the uniform flow automatically, and satisfy the geometric conservation law (GCL). The numerical accuracy can be maintained even for a largely moving and deforming mesh. Several test cases are presented to demonstrate the performance of the gas-kinetic DG-ALE method.
NASA Astrophysics Data System (ADS)
Vennila, Krishnan; Chitra, Loganathan; Balagurunathan, Rama; Palvannan, Thayumanavan
2018-03-01
Selenium and silver nanoparticles (NPs) were synthesized using Spermacoce hispida aqueous leaf extract (Sh-ALE). The optimum condition required for the synthesis of Sh-SeNPs was found to be 30 mM selenious acid solution to Sh-ALE at the ratio of 4:46, pH 9, incubated at 40 °C for 10 min. On the other hand, for Sh-AgNPs the optimum condition was found to be 1 mM AgNO3 to the Sh-ALE solution at the ratio of 4:46, pH 8, incubated at 40 °C for 10 min. SEM analysis revealed that both the Sh-AgNPs and Sh-SeNPs are predominantly rod-shaped. Sh-SeNPs and Sh-AgNPs were found to possess concentration-dependent antioxidant activity. However, Sh-SeNPs showed potent anti-inflammatory property, antibacterial property and anticancer activity against human cervical cancer cell in comparison to Sh-AgNPs. Phytochemical analysis, FTIR and GC-MS analysis showed that various flavonoids, saponins and phenolic compounds present in Sh-ALE catalysed the formation of NPs. Also, GC-MS analysis revealed that Sh-SeNPs are capped by synaptogenin B and derivatives of apigenin, quinoline and quinazoline. The advantage of attachment of such phytoconstituents on Sh-SeNPs for its potent biological activity in comparison to Sh-AgNPs is evident in in vitro conditions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burton, Donald E.; Morgan, Nathaniel Ray; Charest, Marc Robert Joseph
From the very origins of numerical hydrodynamics in the Lagrangian work of von Neumann and Richtmyer [83], the issue of total energy conservation as well as entropy production has been problematic. Because of well known problems with mesh deformation, Lagrangian schemes have evolved into Arbitrary Lagrangian–Eulerian (ALE) methods [39] that combine the best properties of Lagrangian and Eulerian methods. Energy issues have persisted for this class of methods. We believe that fundamental issues of energy conservation and entropy production in ALE require further examination. The context of the paper is an ALE scheme that is extended in the sense thatmore » it permits cyclic or periodic remap of data between grids of the same or differing connectivity. The principal design goals for a remap method then consist of total energy conservation, bounded internal energy, and compatibility of kinetic energy and momentum. We also have secondary objectives of limiting velocity and stress in a non-directional manner, keeping primitive variables monotone, and providing a higher than second order reconstruction of remapped variables. Particularly, the new contributions fall into three categories associated with: energy conservation and entropy production, reconstruction and bounds preservation of scalar and tensor fields, and conservative remap of nonlinear fields. Our paper presents a derivation of the methods, details of implementation, and numerical results for a number of test problems. The methods requires volume integration of polynomial functions in polytopal cells with planar facets, and the requisite expressions are derived for arbitrary order.« less
Light-Induced Retinopathy: Young Age Protects more than Ocular Pigmentation.
Polosa, Anna; Bessaklia, Hyba; Lachapelle, Pierre
2017-06-01
The purpose of this study was to compare the efficacy that ocular melanin confers in protecting the retina of juvenile and adult rats exposed to a bright luminous environment. Juvenile (JLE) and adult (ALE) Long-Evans pigmented rats were thus exposed to a bright cyclic light (10,000lux; white light) from postnatal day 14-28 or for 6 consecutive days, respectively. Flash electroretinograms (ERG) and retinal histology were performed at different predetermined ages, post-light exposure. Despite a significant reduction in ERG responses immediately following light exposure, with time, retinal function fully recovered in JLE compared to a 54% recovery for the ALE. In ALE, we noted a region of the supero-temporal quadrant that was highly vulnerable to light damage. This region was also devoid of melanin granules prior to the light exposure. This melanin-free zone increased in size in the days that followed the end of exposure, a process that was accompanied by the gradual degeneration of the thus uncovered photoreceptors. In contrast, melanin and photoreceptor losses were minimal in JLE. Our results suggest that the light-induced photoreceptor degeneration in ALE would be secondary to the initial destruction of the RPE and ensuing loss of melanin protection. In contrast, the melanin granules of JLE appear to be significantly more resistant to light damage, a characteristic that would explain the higher resistance of JLE photoreceptors to light damage. Our results would thus suggest that the efficacy of ocular melanin protection against light damage declines with age.
Dunn, Andrea L; Buller, David B; Dearing, James W; Cutter, Gary; Guerra, Michele; Wilcox, Sara; Bettinghaus, Erwin P
2012-06-01
BACKGROUND: There is a scarcity of research studies that have examined academic-commercial partnerships to disseminate evidence-based physical activity programs. Understanding this approach to dissemination is essential because academic-commercial partnerships are increasingly common. Private companies have used dissemination channels and strategies to a degree that academicians have not, and declining resources require academicians to explore these partnerships. PURPOSE: This paper describes a retrospective case-control study design including the methods, demographics, organizational decision-making, implementation rates, and marketing strategy for Active Living Every Day (ALED), an evidence-based lifestyle physical activity program that has been commercially available since 2001. Evidence-based public health promotion programs rely on organizations and targeted sectors to disseminate these programs although relatively little is known about organizational-level and sector-level influences that lead to their adoption and implementation. METHODS: Cases (n=154) were eligible if they had signed an ALED license agreement with Human Kinetics (HK), publisher of the program's textbooks and facilitator manuals, between 2001 and 2008. Two types of controls were matched (2:2:1) and stratified by sector and region. Active controls (Control 1; n=319) were organizations that contacted HK to consider adopting ALED. Passive controls (Control 2; n=328) were organizations that received unsolicited marketing materials and did not initiate contact with HK. We used Diffusion of Innovations Theory (DIT) constructs as the basis for developing the survey of cases and controls. RESULTS: Using the multi-method strategy recommended by Dillman, a total of n=801 cases and controls were surveyed. Most organizations were from the fitness sector followed by medical, nongovernmental, governmental, educational, worksite and other sectors with significantly higher response rates from government, educational and medical sectors compared with fitness and other sectors, (p=0.02). More cases reported being involved in the decision to adopt ALED (p<0.0001). Data indicate that a low percentage of controls had ever heard of ALED despite repeated marketing and offering other types of physical activity programs and services. Finally, slightly over half of the adopters reported they had actually implemented the ALED program. CONCLUSION: Dissemination research requires new perspectives and designs to produce valid insights about the results of dissemination efforts. This study design, survey methods and theoretically-based questions can serve as a useful model for other evidence-based public health interventions that are marketed by commercial publishers to better understand key issues related to adoption and implementation of evidence-based programs.
Perot, G; Clarençon, F; Di Maria, F; Sourour, N; Biondi, A; Cornu, P; Chiras, J
2011-10-01
Persistent trigeminal artery is a rare persistent carotid-basilar anastomosis that usually connect the infracavernous segment of the ICA with the basilar artery. Rarely, PTA may feed cerebellar artery. We describe an exceptional case of PTA terminating in postero-inferior cerebellar artery (PICA) hemispheric branch. Angiographic and CTA features are presented and hypotheses regarding developmental origin of this variation are discussed. Copyright © 2011. Published by Elsevier Masson SAS.
Patterns and Variations in Microvascular Decompression for Trigeminal Neuralgia
TODA, Hiroki; GOTO, Masanori; IWASAKI, Koichi
2015-01-01
Microvascular decompression (MVD) is a highly effective surgical treatment for trigeminal neuralgia (TN). Although there is little prospective clinical evidence, accumulated observational studies have demonstrated the benefits of MVD for refractory TN. In the current surgical practice of MVD for TN, there have been recognized patterns and variations in surgical anatomy and various decompression techniques. Here we provide a stepwise description of surgical procedures and relevant anatomical characteristics, as well as procedural options. PMID:25925756
Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain.
Bagues, Ana; Martín, María Isabel; Higuera-Matas, Alejandro; Esteban-Hernández, Jesús; Ambrosio, Emilio; Sánchez-Robles, Eva María
2018-04-01
Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% confidence interval, 33.3-53.9) in the trigeminal ganglia than in the spinal one. The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain.
Li, Kang-Wu; Yu, Yanhui Peter; Zhou, Chunyi; Kim, Doo-Sik; Lin, Bin; Sharp, Kelli; Steward, Oswald; Luo, Z. David
2014-01-01
To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2. PMID:24459143
Arslan, Mehmet; Deda, Haluk; Avci, Emel; Elhan, Alaittin; Tekdemir, Ibrahim; Tubbs, R Shane; Silav, Gokalp; Yilmaz, Erdal; Baskaya, Mustafa Kemal
2012-01-01
Surgical approaches to Meckel's cave (MC) are often technically difficult and sometimes associated with postoperative morbidity. The relationship of surgical landmarks to relevant anatomy is important. Therefore, we attempted to delineate quantitatively their anatomy and the relationships between MC and surrounding structures. With the aid of a surgical microscope, MC and its contents were studied in 15 formalin-fixed cadaver head specimens. Measurements were made and their relationships were observed. The distance from the zygomatic arch and the lateral end of the petrous ridge to MC was 26.5 and 34.4 mm, respectively. The distance from the arcuate eminence, the facial nerve hiatus, and the foramen spinosum to MC was 16.6, 12.8 and 7.46 mm respectively. The TG lay 5.81 mm posterior to the foramen ovale. The distance from the abducens, trochlear and oculomotor nerves to the trigeminal ganglion was 1.87, 5.53 and 6.57 mm respectively. The distance from the posterior and the anterior walls of the sigmoid sinus to the trigeminal porus was 43.6 and 33.1 mm respectively. The trigeminal porus was on average 7.19 mm from the anterior wall of the internal acoustic meatus. The anatomical landmarks as presented herein regarding MC may be used for a safer skull base approach to the region.
Isolation of virus from brain after immunosuppression of mice with latent herpes simplex
NASA Astrophysics Data System (ADS)
Kastrukoff, Lorne; Long, Carol; Doherty, Peter C.; Wroblewska, Zofia; Koprowski, Hilary
1981-06-01
Herpes simplex virus (HSV) is usually present in a latent form in the trigeminal ganglion of man1-3. Various stress factors may induce virus reactivation, which is manifest by a lip lesion (innervated from the trigeminal ganglion) and the production of infectious virus. The considerable experimental efforts to define the conditions that lead to the reactivation of latent HSV have concentrated on isolating virus either from the original extraneural site of virus inoculation, or from cell-free homogenates of sensory ganglia from latently infected animals4-15. Recent DNA hybridization experiments resulted in the demonstration of the presence of HSV genomes in the brain tissue of both latently infected mice, and of humans who showed no clinical symptoms of HSV (ref. 16 and N. Fraser, personal communication). This led us to consider the possibility that HSV may be present in brain tissue as the result of either reactivation of the virus in brain cells or the passage of reactivated virus from trigeminal ganglia through the brain stem to the brain. The presence of infectious HSV in brain tissue has not previously been demonstrated; yet this could be a factor in chronic, relapsing neurological diseases such as multiple sclerosis. We have now shown experimentally that mice carrying latent HSV in their trigeminal ganglia may, following massive immunosuppression, express infectious virus in the central nervous system (CNS).
[Herpes zoster of the trigeminal nerve: a case report and review of the literature].
Carbone, V; Leonardi, A; Pavese, M; Raviola, E; Giordano, M
2004-01-01
Herpes zoster (shingles) is caused when the varicella zoster virus that has remained latent since an earlier varicella infection (chicken-pox) is reactivated. Herpes Zoster is a less common and endemic disease than varicella: factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Following reactivation, centrifugal migration of herpes zoster virus (HZV) occurs along sensory nerves to produce a characteristic painful cutaneous or mucocutaneous vesicular eruption that is generally limited to the single affected dermatome. Herpes zoster may affect any sensory ganglia and its cutaneous nerve: the most common sites affected are thoracic dermatomes (56%), followed by cranial nerves (13%) and lumbar (13%), cervical (11%) and sacral nerves (4%). Among cranial nerves, the trigeminal and facial nerves are the most affected due to reactivation of HZV latent in gasserian and geniculated ganglia. The 1st division of the trigeminal nerve is commonly affected, whereas the 2nd and the 3rd are rarely involved. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be established before final treatment. A literature review of herpes zoster of the trigeminal nerve is presented and the clinical presentation, differential diagnosis and treatment modalities are underlined. A case report is presented.
Synthetic neurotensin analogues are nontoxic analgesics for the rabbit cornea.
Kim, Charles; Barbut, Denise; Heinemann, Murk H; Pasternak, Gavril; Rosenblatt, Mark I
2014-05-13
To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Strittmatter, M; Grauer, M; Isenberg, E; Hamann, G; Fischer, C; Hoffmann, K H; Blaes, F; Schimrigk, K
1997-04-01
The pathogenesis of trigeminal neuralgia remains largely unknown. "Peripheral" as well as "central" causes have been suggested. To investigate the role of serotonergic, noradrenergic, dopaminergic, and peptidergic systems, we determined the concentrations of epinephrine, norepinephrine, and their breakdown product, vanillylmandelic acid, in the cerebrospinal fluid of 16 patients (55.3 +/- 8.3 years) with trigeminal neuralgia. As a marker for the dopaminergic system, we determined cerebrospinal fluid concentrations of dopamine and its metabolite, homovanillic acid. As a marker for the serotonergic system, we measured cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid. In addition, levels of the neuropeptides, substance P and somatostatin, were determined. The concentration of norepinephrine (P < 0.01) and its metabolite, vanillylmandelic acid, (P < 0.05) were significantly decreased in our patients. The level of the dopamine metabolite, homovanillic acid, was also significantly reduced (P < 0.01). Also significantly decreased was 5-hydroxyindoleacetic acid (P < 0.01). Substance P was significantly elevated (P < 0.05). Somatostatin was significantly decreased (P < 0.05). We hypothesize that the sum of complex neurochemical changes plays a role in the pathogenesis of trigeminal neuralgia. The elevated substance P could support the concept of a neurogenic inflammation in the trigeminovascular system, whereas changes in the monoaminergic transmitters and their metabolites seem to reflect a more central dysfunction possibly due to a longer duration of the disease and an accompanying depression.
Reactive Flow Modeling of Liquid Explosives via ALE3D/Cheetah Simulations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kuo, I W; Bastea, S; Fried, L E
2010-03-10
We carried out reactive flow simulations of liquid explosives such as nitromethane using the hydrodynamic code ALE3D coupled with equations of state and reaction kinetics modeled by the thermochemical code Cheetah. The simulation set-up was chosen to mimic cylinder experiments. For pure unconfined nitromethane we find that the failure diameter and detonation velocity dependence on charge diameter are in agreement with available experimental results. Such simulations are likely to be useful for determining detonability and failure behavior for a wide range of experimental conditions and explosive compounds.
NASA Astrophysics Data System (ADS)
Del Pino, S.; Labourasse, E.; Morel, G.
2018-06-01
We present a multidimensional asymptotic preserving scheme for the approximation of a mixture of compressible flows. Fluids are modelled by two Euler systems of equations coupled with a friction term. The asymptotic preserving property is mandatory for this kind of model, to derive a scheme that behaves well in all regimes (i.e. whatever the friction parameter value is). The method we propose is defined in ALE coordinates, using a Lagrange plus remap approach. This imposes a multidimensional definition and analysis of the scheme.
Instantons on ALE spaces and orbifold partitions
NASA Astrophysics Data System (ADS)
Dijkgraaf, Robbert; Sułkowski, Piotr
2008-03-01
We consider Script N = 4 theories on ALE spaces of Ak-1 type. As is well known, their partition functions coincide with Ak-1 affine characters. We show that these partition functions are equal to the generating functions of some peculiar classes of partitions which we introduce under the name 'orbifold partitions'. These orbifold partitions turn out to be related to the generalized Frobenius partitions introduced by G. E. Andrews some years ago. We relate the orbifold partitions to the blended partitions and interpret explicitly in terms of a free fermion system.
Developing a Learning Algorithm-Generated Empirical Relaxer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mitchell, Wayne; Kallman, Josh; Toreja, Allen
2016-03-30
One of the main difficulties when running Arbitrary Lagrangian-Eulerian (ALE) simulations is determining how much to relax the mesh during the Eulerian step. This determination is currently made by the user on a simulation-by-simulation basis. We present a Learning Algorithm-Generated Empirical Relaxer (LAGER) which uses a regressive random forest algorithm to automate this decision process. We also demonstrate that LAGER successfully relaxes a variety of test problems, maintains simulation accuracy, and has the potential to significantly decrease both the person-hours and computational hours needed to run a successful ALE simulation.
Zhang, Qian; Cao, De-Li; Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing
2016-07-11
Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the trigeminal ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 (-/-) mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 (-/-) mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain.
Agarwal, Anurag; Dhama, Vipin; Manik, Yogesh K; Upadhyaya, M K; Singh, C S; Rastogi, V
2015-02-01
Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in the dermatomal distribution area of trigeminal nerve. Percutaneous balloon compression (PBC) of Gasserian ganglion is an effective, comparatively cheaper and simple therapeutic modality for treatment of TN. Compression secondary to PBC selectively injures the large myelinated A-alfa (afferent) fibers that mediate light touch and does not affect A-delta and C-fibres, which carry pain sensation. Balloon compression reduces the sensory neuronal input, thus turning off the trigger to the neuropathic trigeminal pain. In this current case series, we are sharing our experience with PBC of Gasserian Ganglion for the treatment of idiopathic TN in our patients at an academic university-based medical institution in India. During the period of August 2012 to October 2013, a total of twelve PBCs of Gasserian Ganglion were performed in eleven patients suffering from idiopathic TN. There were nine female patients and two male patients with the age range of 35-70 years (median age: 54 years). In all patients cannulation of foramen ovale was done successfully in the first attempt. In eight out of eleven (72.7%) patients ideal 'Pear-shaped' balloon visualization could be achieved. In the remaining three patients (27.3%), inflated balloon was 'Bullet-shaped'. In one patient final placement of Fogarty balloon was not satisfactory and it ruptured during inflation. This case was deferred for one week when it was completed successfully with 'Pear-shaped' balloon inflation. During the follow up period of 1-13 months, there have been no recurrences of TN. Eight out of eleven patients (72.7%) are completely off medicines (carbamazepine and baclofen) and other two patients are stable on very low doses of carbamazepine. All patients have reported marked improvement in quality of life. This case series shows that percutaneous balloon compression is a useful minimally invasive intervention for the treatment of trigeminal neuralgia.
Effect of image uncertainty on the dosimetry of trigeminal neuralgia irradiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jursinic, Paul A.; Rickert, Kim; Gennarelli, Thomas A.
2005-08-01
Objective: Our objective was to quantify the uncertainty in localization of the trigeminal nerve (TGN) with magnetic resonance imaging (MRI) and computed tomography (CT) and to determine the effect of this uncertainty on gamma-knife dose delivery. Methods: An MR/CT test phantom with 9, 0.6-mm diameter, copper rings was devised. The absolute ring positions in stereotactic space were determined by the angiographic module of the LGP software. The standard deviation, {sigma}, in the difference between the absolute and MR-measured or CT-measured coordinates of the rings was determined. The trigeminal nerve in 52 previously treated patients was contoured and expanded by 1{sigma}more » and 2{sigma} margins to model the uncertainty in the location of the nerve. For gamma-knife treatment, a single isocenter was used and was located at the distal cisternal portion of the trigeminal nerve root. Irradiation methods included a 4-mm collimator, 90 Gy to isocenter and a 4 and 8-mm collimator, 70 Gy to isocenter. A patient outcome survey that sampled pain relief and morbidity was done. Results: The MR coordinate {sigma} was 0.7 mm left-right, 0.8 mm anterior-posterior, and 0.6 mm superior-inferior, and the CT coordinate {sigma} was 0.4 mm left-right, 0.2 mm anterior-posterior, and 0.2 mm superior-inferior. A 45% higher dose line covered the TGN with the 4 and 8-mm method. No significant increase in pain reduction or morbidity occurred. Conclusions: The uncertainty of target location by MRI is more than twice that found in CT imaging. The 4 and 8-mm collimator method covers the trigeminal root cross section with a higher isodose line than does the 4-mm method. This higher dose did not significantly reduce pain or increase morbidity.« less
La fibrose rétropéritonéale: à propos de 12 cas
Majdoub, Aziz El; Khallouk, Abdelhak; Farih, Moulay Hassan
2017-01-01
La fibrose rétropéritonéale (FRP) est une maladie rare. Elle se caractérise par la transformation progressive du tissu adipeux rétopéritonéal en une masse fibreuse qui enserre l'aorte, la veine cave inférieure et les voies urinaires responsable d'une altération progressive de la fonction rénale. Le mode habituel de présentation de cette maladie comporte l'association de douleurs lombaires, d'une insuffisance rénale, et d'un syndrome inflammatoire biologique. Nous rapportons 12 cas de fibrose rétropéritonéale dont nous précisons les particularités cliniques, radiologiques et thérapeutiques. Il s'agit d'une étude rétrospective portant sur douze cas de fibrose rétropéritonéale colligés au service d'urologie au CHU Hassan II de Fès durant une période de 9 ans (2005-2013). Il s'agissait de dix hommes et deux femmes. La symptomatologie clinique était très variable, dominée par la douleur lombaire qui était présente chez tous les malades et une hydrocèle chez un patient. Les explorations biologiques avaient montré une insuffisance rénale chez tous les malades et un syndrome inflammatoire chez dix patients. Le diagnostic de la maladie était suspecté dans tous les cas sur les données de l'échographie qui a montré une obstruction de la voie excrétrice supérieure sans obstacle visible chez tous les malades, et confirmé par la TDM abdominale sans injection du produit de contraste qui objectivait une lésion tissulaire rétropéritonéale engainant les vaisseaux et les voies urinaires. Dans notre série, la fibrose rétropéritonéale était idiopathique dans neuf cas. Elle était péri anévrysmale chez deux malades, et post radiothérapie chez un malade. Tous nos patients avaient bénéficié d'un drainage urinaire par sonde urétérale double J. Sept malades avaient reçu une corticothérapie. Une amélioration clinique et biologique, avec disparition de la douleur et amélioration de l'état général, a été observée chez 6 patients. A travers cette étude nous avons confirmé la rareté de la fibrose rétropéritonéale, la difficulté de son diagnostic, la fréquence de la douleur, du syndrome inflammatoire et de l'insuffisance rénale. La TDM abdominale sans injection du produit de contraste confirme le diagnostic. Le drainage urinaire est indispensable dans la plupart des cas et le suivi régulier des malades est nécessaire. PMID:29610632
[Trigeminal autonomic cephalgias: diagnostic and therapeutic implications].
Rosenberg-Nordmann, Mirjam; Tölle, Thomas R; Sprenger, Till
2007-09-06
Trigeminal autonomic cephalgias (TACs) are primary headache syndromes characterized by severe short-lasting headaches accompanied by ipsilateral facial autonomic symptoms. The group includes cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting neuralgiform headache with conjunctival injection and tearing (SUNCT). By far, Cluster headache is the most frequent of these syndromes. Similar hypothalamic and trigeminovascular mechanisms have been discussed as pathophysiologic mechanisms for all TACs. The therapeutic strategies, however, differ considerably. Although unusual, structural lesions in TACs have been described, affecting the therapeutic management.
The Trigeminal (V) and Facial (VII) Cranial Nerves
Sanders, Richard D.
2010-01-01
There are close functional and anatomical relationships between cranial nerves V and VII in both their sensory and motor divisions. Sensation on the face is innervated by the trigeminal nerves (V) as are the muscles of mastication, but the muscles of facial expression are innervated mainly by the facial nerve (VII) as is the sensation of taste. This article briefly reviews the anatomy of these cranial nerves, disorders of these nerves that are of particular importance to psychiatry, and some considerations for differential diagnosis. PMID:20386632
Moorthy, Advan; Stassen, Leo F A
2015-01-01
Paraesthesia can be a complication of surgical intervention. Its occurrence after dental local anaesthetic use is a rare event in general dental practice. Reported cases have mainly described its presentation for the mandibular division of the trigeminal nerve with very few reports for the maxillary division of this nerve. This report describes a case of paraesthesia in the maxillary region following local anaesthetic use prior to removal of an upper molar tooth.
Forced folding in a salty basin: Gada'-Ale in the Afar
NASA Astrophysics Data System (ADS)
Rafflin, Victoria; Hetherington, Rachel; Hagos, Miruts; van Wyk de Vries, Benjamin
2017-04-01
The Gada'-Ale Volcano in the Danakil Depression of Ethiopia is a curious shield-like, or flat dome-like volcanic centre in the Afar Rift. It has several fissure eruptions seen on its mid and lower flanks. It has an even more curious ring structure on its western side that has been interpreted as a salt diapir. The complex lies the central part of the basin where there are 1-2 km thick salt deposits. The area was active in 1990's (Amelung et al 2000) with no eruptive activity, but a possible intrusion. There was also an intrusion north of Gada'-Ale at Dallol in 2005 (Nobile et al 2012). Using Google Earth imagery, we have mapped the volcano, and note that: a) the main edifice has a thin skin of lava lying light coloured rock; b) that these thin deposits are sliding down the flank of volcano, and thrusting at the base. In doing so, they are breaking into detached plates. The light colour of the deposits, and the ability of the rock to slide on them suggest that are salt; Fractures on and around the volcano form curved patterns, around raised areas with several km diameter. These could be surface expressions of shallow sills. Putting the observations together with the known geology of adjacent centres like Dallol and Alu, we suggest that Gada'-Ale is a forced fold, created over a sill that has either bulged into a laccolith, or risen as a saucer-shaped sill. The upraised salt has caused the thin veneer of volcanics to slide off. That there are eruptive fissures on Gada'-Ale, and possible sill intrusions around the base suggests that the centre lies over a complex of sills that have gradually intruded and bulged the structure to its present level. Eruptions have contribute only a small amount to the whole topography of the edifice. We hope to visit the volcano in March and will being hot-off-the press details back to the EGU!
Retinal compensatory changes after light damage in albino mice
Montalbán-Soler, Luis; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Salinas-Navarro, Manuel; Galindo-Romero, Caridad; Bezerra de Sá, Fabrízio; García-Ayuso, Diego; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta
2012-01-01
Purpose To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. Methods BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. Results Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. Conclusions In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function. PMID:22509098
Voxel-Based Morphometry ALE meta-analysis of Bipolar Disorder
NASA Astrophysics Data System (ADS)
Magana, Omar; Laird, Robert
2012-03-01
A meta-analysis was performed independently to view the changes in gray matter (GM) on patients with Bipolar disorder (BP). The meta-analysis was conducted on a Talairach Space using GingerALE to determine the voxels and their permutation. In order to achieve the data acquisition, published experiments and similar research studies were uploaded onto the online Voxel-Based Morphometry database (VBM). By doing so, coordinates of activation locations were extracted from Bipolar disorder related journals utilizing Sleuth. Once the coordinates of given experiments were selected and imported to GingerALE, a Gaussian was performed on all foci points to create the concentration points of GM on BP patients. The results included volume reductions and variations of GM between Normal Healthy controls and Patients with Bipolar disorder. A significant amount of GM clusters were obtained in Normal Healthy controls over BP patients on the right precentral gyrus, right anterior cingulate, and the left inferior frontal gyrus. In future research, more published journals could be uploaded onto the database and another VBM meta-analysis could be performed including more activation coordinates or a variation of age groups.
Extraction of Structural Extracellular Polymeric Substances from Aerobic Granular Sludge
Felz, Simon; Al-Zuhairy, Salah; Aarstad, Olav Andreas; van Loosdrecht, Mark C.M.; Lin, Yue Mei
2016-01-01
To evaluate and develop methodologies for the extraction of gel-forming extracellular polymeric substances (EPS), EPS from aerobic granular sludge (AGS) was extracted using six different methods (centrifugation, sonication, ethylenediaminetetraacetic acid (EDTA), formamide with sodium hydroxide (NaOH), formaldehyde with NaOH and sodium carbonate (Na2CO3) with heat and constant mixing). AGS was collected from a pilot wastewater treatment reactor. The ionic gel-forming property of the extracted EPS of the six different extraction methods was tested with calcium ions (Ca2+). From the six extraction methods used, only the Na2CO3 extraction could solubilize the hydrogel matrix of AGS. The alginate-like extracellular polymers (ALE) recovered with this method formed ionic gel beads with Ca2+. The Ca2+-ALE beads were stable in EDTA, formamide with NaOH and formaldehyde with NaOH, indicating that ALE are one part of the structural polymers in EPS. It is recommended to use an extraction method that combines physical and chemical treatment to solubilize AGS and extract structural EPS. PMID:27768085
Calibration of 3D ALE finite element model from experiments on friction stir welding of lap joints
NASA Astrophysics Data System (ADS)
Fourment, Lionel; Gastebois, Sabrina; Dubourg, Laurent
2016-10-01
In order to support the design of such a complex process like Friction Stir Welding (FSW) for the aeronautic industry, numerical simulation software requires (1) developing an efficient and accurate Finite Element (F.E.) formulation that allows predicting welding defects, (2) properly modeling the thermo-mechanical complexity of the FSW process and (3) calibrating the F.E. model from accurate measurements from FSW experiments. This work uses a parallel ALE formulation developed in the Forge® F.E. code to model the different possible defects (flashes and worm holes), while pin and shoulder threads are modeled by a new friction law at the tool / material interface. FSW experiments require using a complex tool with scroll on shoulder, which is instrumented for providing sensitive thermal data close to the joint. Calibration of unknown material thermal coefficients, constitutive equations parameters and friction model from measured forces, torques and temperatures is carried out using two F.E. models, Eulerian and ALE, to reach a satisfactory agreement assessed by the proper sensitivity of the simulation to process parameters.
History of the pharmacies in the town of Aleşd, Bihor county
PAŞCA, MANUELA BIANCA; GÎTEA, DANIELA; MOISA, CORINA
2013-01-01
In 1848 pharmacist Horváth Mihály established the first pharmacy in Aleşd, called Speranţa (Remény). Following the brief history of this pharmacy we will notice that in 1874 the pharmacy comes into the possession of Kocsiss József. In 1906 the personal rights of the pharmacy are transcribed to Kocsiss Béla, and since 1938 the his son, Kocsiss Dezső, pharmacist, became the new owner. In 1949 the pharmacy was nationalized and became the property of the Pharmaceutical Office Oradea, the pharmacy got the name Farmacia nr. 22 of Aleşd, and continued its activity throughout the whole communist period. Starting with the year 1991 it entered into private system as Angefarm, as the property of Mermeze Gheorghe, pharmacist, and from 2003 until now works under the name Vitalogy 3, as the property of Ghitea Sorin. A second pharmacy, Sfântul Anton was founded in 1937 by pharmacist Herceg Dobreanu Atena, which however had no continuity during the communist period. PMID:26527963
Durham, Paul L.
2018-01-01
The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype. PMID:27334137
Davies, A; Lumsden, A
1983-01-01
Trigeminal ganglia have been removed from five, six, seven and eight day chick embryos and explants of the dorso-medial (DM) and ventro-lateral (VL) parts of the maxillomandibular lobe were grown in tissue culture. Quantitative methods were used to assess the influence of nerve growth factor (NGF) on fiber outgrowth from these explants. At all ages outgrowth from DM explants was significantly greater than from VL explants, the difference being most pronounced between the extreme DM and VL poles of the maxillomandibular lobe. These observations are interpreted as indicating the existence of two distinct populations of neurons in terms of their response to NGF rather than the consequence of the asynchronous differentiation and maturation of the VL and DM neurons. A similar study of 10, 11 and 12 day embryonic mouse trigeminal ganglia revealed no significant difference in neurite outgrowth between DM and VL regions grown in the presence or absence of NGF. Copyright © 1983. Published by Elsevier Ltd.
Gagliardo, A; Ioalè, P; Savini, M; Wild, J M
2006-08-01
The ability of pigeons to find their way home from unfamiliar sites located up to hundreds of kilometers away is well known, but the mechanisms underlying this ability remain controversial. One proposed mechanism is based on the suggestion that pigeons are equipped with magnetoreceptors that can enable the detection of either the earth's magnetic field and/or magnetic field anomalies in the local terrain over which the pigeons fly. Recent reports have suggested that these magnetoreceptors are located in the upper beak where they are innervated by the ophthalmic branch of the trigeminal nerve. Moreover, this nerve has been shown to mediate pigeons' ability to discriminate the presence versus the absence of a magnetic field anomaly in a conditioning situation. In the present study, however, we show that an intact ophthalmic branch of the trigeminal nerve is neither necessary nor sufficient for good homing performance from unfamiliar locations, but that an intact olfactory nerve is necessary.
Kim, Hye-Jin; Lee, Geun-Woo; Kim, Min-Ji; Yang, Kui-Ye; Kim, Seong-Taek; Bae, Yong-Cheol
2015-01-01
We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions. PMID:26170739
Visual but not trigeminal mediation of magnetic compass information in a migratory bird.
Zapka, Manuela; Heyers, Dominik; Hein, Christine M; Engels, Svenja; Schneider, Nils-Lasse; Hans, Jörg; Weiler, Simon; Dreyer, David; Kishkinev, Dmitry; Wild, J Martin; Mouritsen, Henrik
2009-10-29
Magnetic compass information has a key role in bird orientation, but the physiological mechanisms enabling birds to sense the Earth's magnetic field remain one of the unresolved mysteries in biology. Two biophysical mechanisms have become established as the most promising magnetodetection candidates. The iron-mineral-based hypothesis suggests that magnetic information is detected by magnetoreceptors in the upper beak and transmitted through the ophthalmic branch of the trigeminal nerve to the brain. The light-dependent hypothesis suggests that magnetic field direction is sensed by radical pair-forming photopigments in the eyes and that this visual signal is processed in cluster N, a specialized, night-time active, light-processing forebrain region. Here we report that European robins with bilateral lesions of cluster N are unable to show oriented magnetic-compass-guided behaviour but are able to perform sun compass and star compass orientation behaviour. In contrast, bilateral section of the ophthalmic branch of the trigeminal nerve in European robins did not influence the birds' ability to use their magnetic compass for orientation. These data show that cluster N is required for magnetic compass orientation in this species and indicate that it may be specifically involved in processing of magnetic compass information. Furthermore, the data strongly suggest that a vision-mediated mechanism underlies the magnetic compass in this migratory songbird, and that the putative iron-mineral-based receptors in the upper beak connected to the brain by the trigeminal nerve are neither necessary nor sufficient for magnetic compass orientation in European robins.
Trigeminal neuralgia post-styloidectomy in Eagle syndrome: a case report
2012-01-01
Introduction Eagle syndrome is a condition characterized by an elongated (>3cm) styloid process with associated symptoms of recurrent facial or throat pain. In this report we present a case of Eagle syndrome exhibiting the typical findings of glossopharyngeal nerve involvement, as well as unusual involvement of the trigeminal nerve. Notably, this patient developed a classical trigeminal neuralgia post-styloidectomy. Case presentation A 68-year-old Caucasian woman presented with a 25-year history of dull pain along the right side of her throat, lateral neck, and jaw. Her symptoms were poorly controlled with medication until 15 years ago when she was diagnosed with Eagle syndrome, and underwent a manual fracture of her styloid process. This provided symptomatic relief until 5 years ago when the pain recurred and progressed. She underwent a styloidectomy via a lateral neck approach, which resolved the pain once again. However, 6 months ago a new onset of triggerable, electric shock-like facial pain began within the right V1 and V2 distributions. Conclusions Eagle syndrome is distressing to patients and often difficult to diagnose due to its wide variability in symptoms. It is easily confused with dental pain or temporomandibular joint disorder, leading to missed diagnoses and unnecessary procedures. Pain along the jaw and temple is an unusual but possible consequence of Eagle syndrome. An elongated styloid process should be considered a possible etiology of dull facial pain in the trigeminal distributions, in particular V3. PMID:23031688
Gamma knife radiosurgery for cerebellopontine angle epidermoid tumors.
El-Shehaby, Amr M N; Reda, Wael A; Abdel Karim, Khaled M; Emad Eldin, Reem M; Nabeel, Ahmed M
2017-01-01
Intracranial epidermoid tumors are commonly found in the cerebellopontine angle where they usually present with either trigeminal neuralgia or hemifacial spasm. Radiosurgery for these tumors has rarely been reported. The purpose of this study is to assess the safety and clinical outcome of the treatment of cerebellopontine epidermoid tumors with gamma knife radiosurgery. This is a retrospective study involving 12 patients harboring cerebellopontine angle epidermoid tumors who underwent 15 sessions of gamma knife radiosurgery. Trigeminal pain was present in 8 patients and hemifacial spasm in 3 patients. All cases with trigeminal pain were receiving medication and still uncontrolled. One patient with hemifacial spasm was medically controlled before gamma knife and the other two were not. Two patients had undergone surgical resection prior to gamma knife treatment. The median prescription dose was 11 Gy (10-11 Gy). The tumor volumes ranged from 3.7 to 23.9 cc (median 10.5 cc). The median radiological follow up was 2 years (1-5 years). All tumors were controlled and one tumor shrank. The median clinical follow-up was 5 years. The trigeminal pain improved or disappeared in 5 patients, and of these, 4 cases stopped their medication and one decreased it. The hemifacial spasm resolved in 2 patients who were able to stop their medication. Facial palsy developed in 1 patient and improved with conservative treatment. Transient diplopia was also reported in 2 cases. Gamma knife radiosurgery provides good clinical control for cerebellopontine angle epidermoid tumors.
Gamma knife radiosurgery for cerebellopontine angle epidermoid tumors
El-Shehaby, Amr M. N.; Reda, Wael A.; Abdel Karim, Khaled M.; Emad Eldin, Reem M.; Nabeel, Ahmed M.
2017-01-01
Background: Intracranial epidermoid tumors are commonly found in the cerebellopontine angle where they usually present with either trigeminal neuralgia or hemifacial spasm. Radiosurgery for these tumors has rarely been reported. The purpose of this study is to assess the safety and clinical outcome of the treatment of cerebellopontine epidermoid tumors with gamma knife radiosurgery. Methods: This is a retrospective study involving 12 patients harboring cerebellopontine angle epidermoid tumors who underwent 15 sessions of gamma knife radiosurgery. Trigeminal pain was present in 8 patients and hemifacial spasm in 3 patients. All cases with trigeminal pain were receiving medication and still uncontrolled. One patient with hemifacial spasm was medically controlled before gamma knife and the other two were not. Two patients had undergone surgical resection prior to gamma knife treatment. The median prescription dose was 11 Gy (10–11 Gy). The tumor volumes ranged from 3.7 to 23.9 cc (median 10.5 cc). Results: The median radiological follow up was 2 years (1–5 years). All tumors were controlled and one tumor shrank. The median clinical follow-up was 5 years. The trigeminal pain improved or disappeared in 5 patients, and of these, 4 cases stopped their medication and one decreased it. The hemifacial spasm resolved in 2 patients who were able to stop their medication. Facial palsy developed in 1 patient and improved with conservative treatment. Transient diplopia was also reported in 2 cases. Conclusion: Gamma knife radiosurgery provides good clinical control for cerebellopontine angle epidermoid tumors. PMID:29184709
Abbey, Marcie J.; Patil, Vinit V.; Vause, Carrie V.; Durham, Paul L.
2008-01-01
Ethnopharmacological relevance Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception. Aim of the study To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken. Results Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl- and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24 h prior to capsaicin treatment repressed the stimulatory effects of capsaicin. Conclusions Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation. PMID:17997062
Abbey, Marcie J; Patil, Vinit V; Vause, Carrie V; Durham, Paul L
2008-01-17
Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception. To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken. Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl- and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24h prior to capsaicin treatment repressed the stimulatory effects of capsaicin. Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation.
Microendoscopic stereotactic-guided percutaneous radiofrequency trigeminal nucleotractotomy.
Teixeira, Manoel Jacobsen; de Almeida, Fabrício Freitas; de Oliveira, Ywzhe Sifuentes Almeida; Fonoff, Erich Talamoni
2012-02-01
Over the past few decades, various authors have performed open or stereotactic trigeminal nucleotractotomy for the treatment of neuropathic facial pain resistant to medical treatment. Stereotactic procedures can be performed percutaneously under local anesthesia, allowing intraoperative neurological examination as a method for target refinement. However, blind percutaneous procedures in the region of the atlantooccipital transition carry a considerably high risk of vascular injuries that may bring prohibitive neurological deficit or even death. To avoid such complications, the authors present the first clinical use of microendoscopy to assist percutaneous radiofrequency trigeminal nucleotractotomy. The aim of this article is to demonstrate intradural microendoscopic visualization of the medulla oblongata through an atlantooccipital percutaneous approach. The authors present a case of severe postherpetic facial neuralgia in a patient who underwent the procedure and had satisfactory results. Stereotactic computational image planning for targeting the spinal trigeminal tract and nucleus in the posterolateral medulla was performed, allowing for an accurate percutaneous approach. Immediately before radiofrequency electrode insertion, a fine endoscope was introduced to visualize the structures in the cisterna magna. Microendoscopic visualization offered clear identification of the pial surface of the medulla oblongata and its blood vessels, the arachnoid membrane, cranial nerve rootlets and their entry zone, and larger vessels such as the vertebral arteries and the branches of the posterior inferior cerebellar artery. The initial application of this technique suggests that percutaneous microendoscopy may be useful for particular manipulation of the medulla oblongata, increasing the safety of the procedure and likely improving its effectiveness.
Carter, E; Yilmaz, Z; Devine, M; Renton, T
2016-06-24
Introduction Sensory neuropathies of the mandibular division of the trigeminal (V3) nerve can be debilitating, causing difficulty with daily function. It has a variety of causes, including iatrogenic injury, usually caused by third molar removal, local anaesthetic administration, implant placement or endodontic treatment. Non-iatrogenic causes include infection, primary or secondary neoplasia and various medical conditions.Objective To review the aetiology, evaluation and management of V3 neuropathy in a retrospective case-series of patients referred to a specialist nerve injury clinic over an eight-year period, particularly focusing on the non-iatrogenic causes of this presentation.Methods A retrospective analysis of the case notes of 372 patients referred to the specialist nerve injury clinic between 2006 and 2014 was carried out to establish the cause of the neuropathy and subsequent management or referral. The assessment protocol of trigeminal neuropathy used in the clinic is also outlined.Results Most patients (89.5%) presented with neuropathy due to iatrogenic injury. Of the non-iatrogenic causes (10.5%), malignancy accounted for a fifth of presentations, and infection almost two-fifths, demonstrating the importance of prompt identification of a cause and management by the clinician, or referral to the appropriate specialty. Other, more rare causes are also presented, including multiple sclerosis, sickle-cell anaemia and Paget's disease, highlighting the importance to the clinician of considering differential diagnoses.Conclusions This case series demonstrates the less frequent, but nevertheless important, non-iatrogenic causes which clinicians should consider when assessing patients with trigeminal neuropathy.
Central effects of acetylsalicylic acid on trigeminal-nociceptive stimuli
2014-01-01
Background Acetylsalicylic acid is one of the most used analgesics to treat an acute migraine attack. Next to the inhibitory effects on peripheral prostaglandin synthesis, central mechanisms of action have also been discussed. Methods Using a standardized model for trigeminal-nociceptive stimulation during fMRI scanning, we investigated the effect of acetylsalicylic acid on acute pain compared to saline in 22 healthy volunteers in a double-blind within-subject design. Painful stimulation was applied using gaseous ammonia and presented in a pseudo-randomized order with several control stimuli. All participants were instructed to rate the intensity and unpleasantness of every stimulus on a VAS scale. Based on previous results, we hypothesized to find an effect of ASA on central pain processing structures like the ACC, SI and SII as well as the trigeminal nuclei and the hypothalamus. Results Even though we did not find any differences in pain ratings between saline and ASA, we observed decreased BOLD signal changes in response to trigemino-nociceptive stimulation in the ACC and SII after administration of ASA compared to saline. This finding is in line with earlier imaging results investigating the effect of ASA on acute pain. Contrary to earlier findings from animal studies, we could not find an effect of ASA on the trigeminal nuclei in the brainstem or within the hypothalamic area. Conclusion Taken together our study replicates earlier findings of an attenuating effect of ASA on pain processing structures, which adds further evidence to a possibly central mechanism of action of ASA. PMID:25201152
Dolera, Mario; Malfassi, Luca; Marcarini, Silvia; Mazza, Giovanni; Carrara, Nancy; Pavesi, Simone; Sala, Massimo; Finesso, Sara; Urso, Gaetano
2018-06-08
The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities. © 2018 American College of Veterinary Radiology.
Laser Ray Tracing in a Parallel Arbitrary Lagrangian-Eulerian Adaptive Mesh Refinement Hydrocode
DOE Office of Scientific and Technical Information (OSTI.GOV)
Masters, N D; Kaiser, T B; Anderson, R W
2009-09-28
ALE-AMR is a new hydrocode that we are developing as a predictive modeling tool for debris and shrapnel formation in high-energy laser experiments. In this paper we present our approach to implementing laser ray-tracing in ALE-AMR. We present the equations of laser ray tracing, our approach to efficient traversal of the adaptive mesh hierarchy in which we propagate computational rays through a virtual composite mesh consisting of the finest resolution representation of the modeled space, and anticipate simulations that will be compared to experiments for code validation.
Etiologie Rare de Sinusites Nosocomiales en Milieu de Reanimation - A Propos d'une Observation
Messadi, A.A.; Oueslati, S.; Thabet, L.; Bousselmi, K.; Menif, E.
2006-01-01
Summary Les sinusites nosocomiales ne sont pas rares en réanimation. Elles surviennent en général dans les suites d'une intubation nasotrachéale voire même orotrachéale. Le tubage gastrique peut être à lui seul à l'origine d'une sinusite nosocomiale. Nous rapportons le cas d'une patiente hospitalisée qui a été victime de brûlures étendues chez qui la sonde nasogastrique a été à l'origine d'une pansinusite dont l'issue a été fatale. PMID:21991055
Assessment of phosphate binding by sevelamer carbonate powder for oral suspension mixed in foods.
Hanus, Martin; Zhorov, Eugene; Brommage, Deborah; Plone, Melissa; Holmes-Farley, Stephen Randall
2012-01-01
This study investigated mixing sevelamer carbonate powder with foods and beverages other than water. Food samples, including applesauce, oatmeal, chicken, protein powder, scrambled eggs, ginger ale, and diet ginger ale, were subjected to an in vitro assay, and the difference in the amount of phosphate bound between samples pre-exposed to foods and samples where the drug was exposed to foods concurrently was determined Under these assay conditions, pre-exposure to sevelamer carbonate powder had no effect on the ability to bind phosphate. Clinical testing is needed to further evaluate this finding.
Hormone-Related Migraine Headaches and Mood Disorders: Treatment with Estrogen Stabilization.
Warnock, Julia K; Cohen, Lawrence J; Blumenthal, Harvey; Hammond, Jordan E
2017-01-01
Because estrogens and the trigeminal system are inherently linked, prescribers who are treating a woman with a hormonally related mood disorder and migraine headaches should consider hormonal options to optimize the patient's treatment. This article discusses the interrelationships of estrogen, serotonin, and the trigeminal system as they relate to menstrual migraine occurrence and hormone-related mood symptoms. In addition, clinical examples are provided to facilitate the prescribers treating women during reproductive transitions in which declining estrogens are related to their suffering. © 2016 Pharmacotherapy Publications, Inc.
The neurosurgical treatment of neuropathic facial pain.
Brown, Jeffrey A
2014-04-01
This article reviews the definition, etiology and evaluation, and medical and neurosurgical treatment of neuropathic facial pain. A neuropathic origin for facial pain should be considered when evaluating a patient for rhinologic surgery because of complaints of facial pain. Neuropathic facial pain is caused by vascular compression of the trigeminal nerve in the prepontine cistern and is characterized by an intermittent prickling or stabbing component or a constant burning, searing pain. Medical treatment consists of anticonvulsant medication. Neurosurgical treatment may require microvascular decompression of the trigeminal nerve. Copyright © 2014 Elsevier Inc. All rights reserved.
Granato, Daniel; Branco, Gabriel Favalli; Faria, José de Assis Fonseca; Cruz, Adriano Gomes
2011-02-01
Epidemiological studies have shown that beer has positive effects on inhibiting atherosclerosis, decreasing the content of serum low-density lipoprotein cholesterol and triglycerides, by acting as in vivo free radical scavenger. In this research, the antioxidant activity of commercial Brazilian beers (n = 29) was determined by the oxygen radical absorbance capacity (ORAC) and 1,1-diphenyl-2-picrylhydrazyl (DPPH(·) ) assays and results were analyzed by chemometrics. The brown ale samples (n = 11) presented higher (P < 0.05) flavonoids (124.01 mg L(-1) ), total phenolics (362.22 mg L(-1) ), non-flavonoid phenolics (238.21 mg L(-1) ), lightness (69.48), redness (35.75), yellowness (55.71), color intensity (66.86), hue angle (59.14), color saturation (0.9620), DPPH(·) values (30.96% inhibition), and ORAC values (3, 659.36 µmol Trolox equivalents L(-1) ), compared to lager samples (n = 18). Brown ale beers presented higher antioxidant properties (P < 0.05) measured by ORAC (1.93 times higher) and DPPH (1.65 times higher) compared to lager beer. ORAC values correlated well with the content of flavonoids (r = 0.47; P = 0.01), total phenolic compounds (r = 0.44; P < 0.01) and DPPH (r = 0.67; P < 0.01). DPPH values also correlated well to the content of flavonoids (r = 0.69; P < 0.01), total phenolic compounds (r = 0.60; P < 0.01), and non-flavonoid compounds (r = 0.46; P = 0.01). The results suggest that brown ale beers, and less significantly lager beers, could be sources of bioactive compounds with suitable free radical scavenging properties. 2010 Society of Chemical Industry.
Bundy, Rafe; Walker, Ann F; Middleton, Richard W; Wallis, Carol; Simpson, Hugh C R
2008-09-01
Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.
Sarawek, Sasiporn; Feistel, Bjoern; Pischel, Ivo; Butterweck, Veronika
2008-02-01
Artichoke (Cynara scolymus L.) leaves have been historically used for the treatment of hyperuricemia and gout, however whether artichoke is truly efficacious for this indication, is still a matter of debate. Thus, the goal of the present study was first to examine the xanthine oxidase (XO) inhibitory activity of an artichoke leaf extract (ALE) and some of its main compounds in vitro and then further test potentially active substances for possible hypouricemic effects using an in vivo rat model. The in vitro study showed that ALE inhibited XO with only minimal inhibitory action (< 5 %) at 100 microg/mL. However, when selected compounds were tested, the caffeic acid derivatives revealed a weak XO inhibitory effect with IC (50) > 100 microM. From the tested flavones the aglycone luteolin potently inhibited XO with an IC (50) value of 1.49 microM. Luteolin 7-O-glucoside and luteolin 7-O-glucuronide showed lower XO inhibition activities with IC (50) values of 19.90 microM and 20.24 microM, respectively. However, oral administration of an aqueous ALE, luteolin, and luteolin 7-O-glucoside did not produce any observable hypouricemic effects after acute oral treatment in potassium oxonate-treated rats. After intraperitoneal injection of luteolin a decrease in uric acid levels was detected suggesting that the hypouricemic effects of luteolin are due to its original form rather than its metabolites produced by the gut flora. In conclusion, an aqueous ALE, caffeic acid derivatives and flavones exerted XO inhibitory effects in vitro but a hypouricemic activity could not be confirmed after oral administration.
Modeling The Shock Initiation of PBX-9501 in ALE3D
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leininger, L; Springer, H K; Mace, J
The SMIS (Specific Munitions Impact Scenario) experimental series performed at Los Alamos National Laboratory has determined the 3-dimensional shock initiation behavior of the HMX-based heterogeneous high explosive, PBX 9501. A series of finite element impact calculations have been performed in the ALE3D [1] hydrodynamic code and compared to the SMIS results to validate the code predictions. The SMIS tests use a powder gun to shoot scaled NATO standard fragments at a cylinder of PBX 9501, which has a PMMA case and a steel impact cover. The SMIS real-world shot scenario creates a unique test-bed because many of the fragments arrivemore » at the impact plate off-center and at an angle of impact. The goal of this model validation experiments is to demonstrate the predictive capability of the Tarver-Lee Ignition and Growth (I&G) reactive flow model [2] in this fully 3-dimensional regime of Shock to Detonation Transition (SDT). The 3-dimensional Arbitrary Lagrange Eulerian hydrodynamic model in ALE3D applies the Ignition and Growth (I&G) reactive flow model with PBX 9501 parameters derived from historical 1-dimensional experimental data. The model includes the off-center and angle of impact variations seen in the experiments. Qualitatively, the ALE3D I&G calculations accurately reproduce the 'Go/No-Go' threshold of the Shock to Detonation Transition (SDT) reaction in the explosive, as well as the case expansion recorded by a high-speed optical camera. Quantitatively, the calculations show good agreement with the shock time of arrival at internal and external diagnostic pins. This exercise demonstrates the utility of the Ignition and Growth model applied in a predictive fashion for the response of heterogeneous high explosives in the SDT regime.« less
Li, Na; Lu, Zhan-ying; Yu, Li-hua; Burnstock, Geoffrey; Deng, Xiao-ming; Ma, Bei
2014-03-18
ATP and P2X receptors play important roles in the modulation of trigeminal neuropathic pain, while the role of G protein-coupled P2Y₂ receptors and the underlying mechanisms are less clear. The threshold and frequency of action potentials, fast inactivating transient K+ channels (IA) are important regulators of membrane excitability in sensory neurons because of its vital role in the control of the spike onset. In this study, pain behavior tests, QT-RT-PCR, immunohistochemical staining, and patch-clamp recording, were used to investigate the role of P2Y₂ receptors in pain behaviour. In control rats: 1) UTP, an agonist of P2Y₂/P2Y₄ receptors, caused a significant decrease in the mean threshold intensities for evoking action potentials and a striking increase in the mean number of spikes evoked by TG neurons. 2) UTP significantly inhibited IA and the expression of Kv1.4, Kv3.4 and Kv4.2 subunits in TG neurons, which could be reversed by the P2 receptor antagonist suramin and the ERK antagonist U0126. In ION-CCI (chronic constriction injury of infraorbital nerve) rats: 1) mRNA levels of Kv1.4, Kv3.4 and Kv4.2 subunits were significantly decreased, while the protein level of phosphorylated ERK was significantly increased. 2) When blocking P2Y₂ receptors by suramin or injection of P2Y2R antisense oligodeoxynucleotides both led to a time- and dose-dependent reverse of allodynia in ION-CCI rats. 3) Injection of P2Y₂ receptor antisense oligodeoxynucleotides induced a pronounced decrease in phosphorylated ERK expression and a significant increase in Kv1.4, Kv3.4 and Kv4.2 subunit expression in trigeminal ganglia. Our data suggest that inhibition of P2Y₂ receptors leads to down-regulation of ERK-mediated phosphorylation and increase of the expression of I(A)-related Kv channels in trigeminal ganglion neurons, which might contribute to the clinical treatment of trigeminal neuropathic pain.
Drinovac Vlah, V; Filipović, B; Bach-Rojecky, L; Lacković, Z
2018-03-01
Although botulinum toxin type A (BT-A) is approved for chronic migraine treatment, its site and mechanism of action are still elusive. Recently our group discovered that suppression of CGRP release from dural nerve endings might account for antimigraine action of pericranially injected BT-A. We demonstrated that central antinociceptive effect of BT-A in sciatic region involves endogenous opioid system as well. Here we investigated possible interaction of BT-A with endogenous opioid system within the trigeminal region. In orofacial formalin test we investigated the influence of centrally acting opioid antagonist naltrexone (2 mg/kg, s.c.) versus peripherally acting methylnaltrexone (2 mg/kg, s.c.) on BT-A's (5 U/kg, s.c. into whisker pad) or morphine's (6 mg/kg, s.c.) antinociceptive effect and the effect on dural neurogenic inflammation (DNI). DNI was assessed by Evans blue-plasma protein extravasation. Naltrexone abolished the effect of BT-A on pain and dural plasma protein extravasation, whereas peripherally acting methylnaltrexone did not change either BT-A's effect on pain or its effect on dural extravasation. Naltrexone abolished the antinociceptive and anti-inflammatory effects of morphine, as well. However, methylnaltrexone decreased the antinociceptive effect of morphine only partially in the second phase of the test and had no significant effect on morphine-mediated reduction in DNI. Morphine acts on pain in trigeminal region both peripherally and centrally, whereas the effect on dural plasma protein extravasation seems to be only centrally mediated. However, the interaction of BT-A with endogenous opioid system, with consequent inhibition of nociceptive transmission as well as the DNI, occurs primarily centrally. Botulinum toxin type A (BT-A)'s axonal transport and potential transcytosis suggest that its antinociceptive effect might involve diverse neurotransmitters at different sites of trigeminal system. Here we discovered that the reduction in pain and accompanying DNI involves the interaction of BT-A with central endogenous opioid system (probably at the level of trigeminal nucleus caudalis). © 2017 European Pain Federation - EFIC®.
Jürgens, Tim P; Reetz, Romy; May, Arne
2013-04-10
Nasal insufflation of CO2 has been shown to exert antinociceptive respectively antihyperalgesic effects in animal pain models using topical capsaicin with activation of TRPV1-receptor positive nociceptive neurons. Clinical benefit from CO2 inhalation in patients with craniofacial pain caused by a putative activation of TRPV1 receptor positive trigeminal neurons has also been reported. These effects are probably mediated via an activation of TRPV1 receptor - positive neurons in the nasal mucosa with subsequent central inhibitory effects (such as conditioned pain modulation). In this study, we aimed to examine the effects of intranasal CO2 on a human model of craniofacial pain elicited by nasal application of capsaicin. In a first experiment, 48 healthy volunteers without previous craniofacial pain received intranasal capsaicin to provoke trigeminal pain elicited by activation of TRVP1 positive nociceptive neurons. Then, CO2 or air was insufflated alternatingly into the nasal cavity at a flow rate of 1 l/min for 60 sec each. In the subsequent experiment, all participants were randomized into 2 groups of 24 each and received either continuous nasal insufflation of CO2 or placebo for 18:40 min after nociceptive stimulation with intranasal capsaicin. In both experiments, pain was rated on a numerical rating scale every 60 sec. Contrary to previous animal studies, the effects of CO2 on experimental trigeminal pain were only marginal. In the first experiment, CO2 reduced pain ratings only minimally by 5.3% compared to air if given alternatingly with significant results for the main factor GROUP (F1,47=4.438; p=0.041) and the interaction term TIME*GROUP (F2.6,121.2=3.3; p=0.029) in the repeated-measures ANOVA. However, these effects were abrogated after continuous insufflation of CO2 or placebo with no significant changes for the main factors or the interaction term. Although mild modulatory effects of low-flow intranasal CO2 could be seen in this human model of TRPV-1 mediated activation of nociceptive trigeminal neurons, utility is limited as observed changes in pain ratings are clinically non-significant.
Follow your nose: Implicit spatial processing within the chemosensory systems.
Wudarczyk, Olga A; Habel, Ute; Turetsky, Bruce I; Gur, Raquel E; Kellermann, Thilo; Schneider, Frank; Moessnang, Carolin
2016-11-01
Although most studies agree that humans cannot smell in stereo, it was recently suggested that olfactory localization is possible when assessed implicitly. In a spatial cueing paradigm, lateralized olfactory cues impaired the detection of congruently presented visual targets, an effect contrary to the typical facilitation observed in other sensory domains. Here, we examined the specificity and the robustness of this finding by studying implicit localization abilities in another chemosensory system and by accounting for possible confounds in a modified paradigm. Sixty participants completed a spatial cueing task along with an explicit localization task, using trigeminal (Experiment 1) and olfactory (Experiment 2) stimuli. A control task was implemented to control for residual somatosensory stimulation (Experiment 3). In the trigeminal experiment, stimuli were localized with high accuracy on the explicit level, while the cueing effect in form of facilitation was limited to response accuracy. In the olfactory experiment, responses were slowed by congruent cues on the implicit level, while no explicit localization was observed. Our results point to the robustness of the olfactory interference effect, corroborating the implicit-explicit dissociation of olfactory localization, and challenging the view that humans lost the ability to extract spatial information from smell. The absence of a similar interference for trigeminal cues suggests distinct implicit spatial processing mechanisms within the chemosensory systems. Moreover, the lack of a typical facilitation effect in the trigeminal domain points to important differences from spatial information processing in other, nonchemosensory domains. The possible mechanisms driving the effects are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Stratford, J M; Larson, E D; Yang, R; Salcedo, E; Finger, T E
2017-07-01
Taste buds contain multiple cell types with each type expressing receptors and transduction components for a subset of taste qualities. The sour sensing cells, Type III cells, release serotonin (5-HT) in response to the presence of sour (acidic) tastants and this released 5-HT activates 5-HT 3 receptors on the gustatory nerves. We show here, using 5-HT 3A GFP mice, that 5-HT 3 -expressing nerve fibers preferentially contact and receive synaptic contact from Type III taste cells. Further, these 5-HT 3 -expressing nerve fibers terminate in a restricted central-lateral portion of the nucleus of the solitary tract (nTS)-the same area that shows increased c-Fos expression upon presentation of a sour tastant (30 mM citric acid). This acid stimulation also evokes c-Fos in the laterally adjacent mediodorsal spinal trigeminal nucleus (DMSp5), but this trigeminal activation is not associated with the presence of 5-HT 3 -expressing nerve fibers as it is in the nTS. Rather, the neuronal activation in the trigeminal complex likely is attributable to direct depolarization of acid-sensitive trigeminal nerve fibers, for example, polymodal nociceptors, rather than through taste buds. Taken together, these findings suggest that transmission of sour taste information involves communication between Type III taste cells and 5-HT 3 -expressing afferent nerve fibers that project to a restricted portion of the nTS consistent with a crude mapping of taste quality information in the primary gustatory nucleus. © 2017 Wiley Periodicals, Inc.
Franceschini, Alessia; Nair, Asha; Bele, Tanja; van den Maagdenberg, Arn Mjm; Nistri, Andrea; Fabbretti, Elsa
2012-11-21
Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons.
Abushik, Polina A; Niittykoski, Minna; Giniatullina, Raisa; Shakirzyanova, Anastasia; Bart, Genevieve; Fayuk, Dmitriy; Sibarov, Dmitry A; Antonov, Sergei M; Giniatullin, Rashid
2014-04-01
Recent studies suggested contribution of homocysteine (HCY) to neurodegenerative disorders and migraine. However, HCY effect in the nociceptive system is essentially unknown. To explore the mechanism of HCY action, we studied short- and long-term effects of this amino acid on rat peripheral and central neurons. HCY induced intracellular Ca²⁺ transients in cultured trigeminal neurons and satellite glial cells (SGC), which were blocked by the NMDA antagonist AP-5 in neurons, but not in SGCs. In contrast, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP), the metabotropic mGluR5 (metabotropic glutamate receptor 5 subtype) antagonist, preferentially inhibited Ca²⁺ transients in SGCs. Prolonged application of HCY induced apoptotic cell death of both kinds of trigeminal cells. The apoptosis was blocked by AP-5 or by the mGluR5 antagonist MTEP. Likewise, in cortical neurons, HCY-induced cell death was inhibited by AP-5 or MTEP. Imaging with 2',7'-dichlorodihydrofluorescein diacetate or mitochondrial dye Rhodamine-123 as well as thiobarbituric acid reactive substances assay did not reveal involvement of oxidative stress in the action of HCY. Thus, elevation of intracellular Ca²⁺ by HCY in neurons is mediated by NMDA and mGluR5 receptors while SGC are activated through the mGluR5 subtype. Long-term neurotoxic effects in peripheral and central neurons involved both receptor types. Our data suggest glutamatergic mechanisms of HCY-induced sensitization and apoptosis of trigeminal nociceptors. © 2013 International Society for Neurochemistry.
NASA Astrophysics Data System (ADS)
Feistauer, Miloslav; Kučera, Václav; Prokopová, Jaroslav; Horáček, Jaromír
2010-09-01
The aim of this work is the simulation of viscous compressible flows in human vocal folds during phonation. The computational domain is a bounded subset of IR2, whose geometry mimics the shape of the human larynx. During phonation, parts of the solid impermeable walls are moving in a prescribed manner, thus simulating the opening and closing of the vocal chords. As the governing equations we take the compressible Navier-Stokes equations in ALE form. Space semidiscretization is carried out by the discontinuous Galerkin method combined with a linearized semi-implicit approach. Numerical experiments are performed with the resulting scheme.
An improved design method for EPC middleware
NASA Astrophysics Data System (ADS)
Lou, Guohuan; Xu, Ran; Yang, Chunming
2014-04-01
For currently existed problems and difficulties during the small and medium enterprises use EPC (Electronic Product Code) ALE (Application Level Events) specification to achieved middleware, based on the analysis of principle of EPC Middleware, an improved design method for EPC middleware is presented. This method combines the powerful function of MySQL database, uses database to connect reader-writer with upper application system, instead of development of ALE application program interface to achieve a middleware with general function. This structure is simple and easy to implement and maintain. Under this structure, different types of reader-writers added can be configured conveniently and the expandability of the system is improved.
Overview of SPH-ALE applications for hydraulic turbines in ANDRITZ Hydro
NASA Astrophysics Data System (ADS)
Rentschler, M.; Marongiu, J. C.; Neuhauser, M.; Parkinson, E.
2018-02-01
Over the past 13 years, ANDRITZ Hydro has developed an in-house tool based on the SPH-ALE method for applications in flow simulations in hydraulic turbines. The initial motivation is related to the challenging simulation of free surface flows in Pelton turbines, where highly dynamic water jets interact with rotating buckets, creating thin water jets traveling inside the housing and possibly causing disturbances on the runner. The present paper proposes an overview of industrial applications allowed by the developed tool, including design evaluation of Pelton runners and casings, transient operation of Pelton units and free surface flows in hydraulic structures.
ALE Meta-Analysis of Schizophrenics Performing the N-Back Task
NASA Astrophysics Data System (ADS)
Harrell, Zachary
2010-10-01
MRI/fMRI has already proven itself as a valuable tool in the diagnosis and treatment of many illnesses of the brain, including cognitive problems. By exploiting the differences in magnetic susceptibility between oxygenated and deoxygenated hemoglobin, fMRI can measure blood flow in various regions of interest within the brain. This can determine the level of brain activity in relation to motor or cognitive functions and provide a metric for tissue damage or illness symptoms. Structural imaging techniques have shown lesions or deficiencies in tissue volumes in schizophrenics corresponding to areas primarily in the frontal and temporal lobes. These areas are currently known to be involved in working memory and attention, which many schizophrenics have trouble with. The ALE (Activation Likelihood Estimation) Meta-Analysis is able to statistically determine the significance of brain area activations based on the post-hoc combination of multiple studies. This process is useful for giving a general model of brain function in relation to a particular task designed to engage the affected areas (such as working memory for the n-back task). The advantages of the ALE Meta-Analysis include elimination of single subject anomalies, elimination of false/extremely weak activations, and verification of function/location hypotheses.
The ALE/GAGE/AGAGE Network (DB1001)
Prinn, Ronald G. [MIT, Center for Global Change Science; Weiss, Ray F. [University of California, San Diego; Scripps Institution of Oceanography; Krummel, Paul B. [CSIRO Oceans and Atmosphere, Cape Grim; O'Doherty, Simon [University of Bristol, Barbados and Mace Head Stations; Fraser, Paul [CSIRO Oceans and Atmosphere; Muhle, Jens [UCSD Scripps Institution of Oceanography; Cape Matatula Station; Reimann, Stefan [Swiss Federal Laboratories for Materials Science and Research (EMPA); Jungfraujoch Station; Vollmer, Martin [Swiss Federal Laboratories for Materials Science and Research (EMPA); Jungfraujoch Station; Simmonds, Peter G. [University of Bristol, Atmospheric Chemistry Research Group; Mace Head Station; Malone, Michela [University of Urbino; Monte Cimone Station; Arduini, Jgor [University of Urbino; Monte Cimone Station; Lunder, Chris [Norwegian Institute for Air Research; Ny Alesund Station; Hermansen, Ove [Norwegian Inst. for Air Research (NILU), Kjeller (Norway); Ny Alesund Station; Schmidbauer, Norbert [Norwegian Inst. for Air Research (NILU), Kjeller (Norway); Global Network; Young, Dickon [University of Bristol; Ragged Point Station; Wang, Hsiang J. (Ray) [Geogia Institute of Technology, School of Earth and Atmospheric Sciences; Global Network; Huang, Jin; Rigby, Matthew [University of Bristol; Global Network; Harth, Chris [UCSD, Scripps Institutioon of Oceanography; Global Network; Salameh, Peter [UCSD, Scripps Institution of Oceanography; Global Network; Spain, Gerard [National University of Ireland; Global Network; Steele, Paul [CSIRO Oceans and Atmosphere; Global Network; Arnold, Tim; Kim, Jooil [UCSD, Scripps Institution of Oceanography; Global Network; Derek, Nada; mitrevski, Blagoj; Langenfelds, Ray
2008-01-01
In the ALE/GAGE/AGAGE global network program, continuous high frequency gas chromatographic measurements of four biogenic/anthropogenic gases (methane, CH4; nitrous oxide, N2O; hydrogen, H; and carbon monoxide, CO) and several anthropogenic gases that contribute to stratospheric ozone destruction and/or to the greenhouse effect have been carried out at five globally distributed sites for several years. The program, which began in 1978, is divided into three parts associated with three changes in instrumentation: the Atmospheric Lifetime Experiment (ALE), which used Hewlett Packard HP5840 gas chromatographs; the Global Atmospheric Gases Experiment (GAGE), which used HP5880 gas chromatographs; and the present Advanced GAGE (AGAGE). AGAGE uses two types of instruments: a gas chromatograph with multiple detectors (GC-MD), and a gas chromatograph with mass spectrometric analysis (GC-MS). Beginning in January 2004, an improved cryogenic preconcentration system (Medusa) replaced the absorption-desorption module in the GC-MS systems at Mace Head and Cape Grim; this provided improved capability to measure a broader range of volatile perfluorocarbons with high global warming potentials. More information may be found at the AGAGE home page: http://agage.eas.gatech.edu/instruments-gcms-medusa.htm.
Toward Improved Fidelity of Thermal Explosion Simulations
NASA Astrophysics Data System (ADS)
Nichols, A. L.; Becker, R.; Howard, W. M.; Wemhoff, A.
2009-12-01
We will present results of an effort to improve the thermal/chemical/mechanical modeling of HMX based explosives like LX04 and LX10 for thermal cook-off The original HMX model and analysis scheme were developed by Yoh et al. for use in the ALE3D modeling framework. The current results were built to remedy the deficiencies of that original model. We concentrated our efforts in four areas. The first area was addition of porosity to the chemical material model framework in ALE3D that is used to model the HMX explosive formulation. This is needed to handle the roughly 2% porosity in solid explosives. The second area was the improvement of the HMX reaction network, which included a reactive phase change model base on work by Henson et al. The third area required adding early decomposition gas species to the CHEETAH material database to develop more accurate equations of state for gaseous intermediates and products. Finally, it was necessary to improve the implicit mechanics module in ALE3D to more naturally handle the long time scales associated with thermal cook-off The application of the resulting framework to the analysis of the Scaled Thermal Explosion (STEX) experiments will be discussed.
The Atmospheric Lifetime Experiment and the Global Atmospheric Gas Experiment (ALE/GAGE)
NASA Technical Reports Server (NTRS)
Rasmussen, R. A.; Khalil, M. Aslam K.
1995-01-01
The ALE/GAGE project was designed to determine the global atmospheric lifetimes of the chlorofluorocarbons CCl3F and CCl2F2 (F-11 and F-12), which had been identified as the main gases that cause stratospheric ozone depletion. The experimental procedures also provided the concentrations of CH3CCl3, CCl4 and N2O. The extended role of the project was to evaluate the mass balances of these gases as well. Methylchloroform (CH3CCl3) serves as a tracer of average atmospheric OH concentrations and hence the oxidizing capacity of the atmosphere. Nitrous oxide (N2O) is a potent greenhouse gas and can also deplete the ozone layer. Measurements of these gases were taken with optimized instruments in the field at a frequency of about 1 sample/hr. Toward the end of the present project methane measurements were added to the program. The final report deals with the research of the Oregon Graduate Institute (OGI) as part of the ALE/GAGE program between 4/1/1988 and 1/31/1991. The report defines the scope of the OGI project, the approach, and the results.
Atomic layer deposition and etching methods for far ultraviolet aluminum mirrors
NASA Astrophysics Data System (ADS)
Hennessy, John; Moore, Christopher S.; Balasubramanian, Kunjithapatham; Jewell, April D.; Carter, Christian; France, Kevin; Nikzad, Shouleh
2017-09-01
High-performance aluminum mirrors at far ultraviolet wavelengths require transparent dielectric materials as protective coatings to prevent oxidation. Reducing the thickness of this protective layer can result in additional performance gains by minimizing absorption losses, and provides a path toward high Al reflectance in the challenging wavelength range of 90 to 110 nm. We have pursued the development of new atomic layer deposition processes (ALD) for the metal fluoride materials of MgF2, AlF3 and LiF. Using anhydrous hydrogen fluoride as a reactant, these films can be deposited at the low temperatures required for large-area surface-finished optics and polymeric diffraction gratings. We also report on the development and application of an atomic layer etching (ALE) procedure to controllably etch native aluminum oxide. Our ALE process utilizes the same chemistry used in the ALD of AlF3 thin films, allowing for a combination of high-performance evaporated Al layers and ultrathin ALD encapsulation without requiring vacuum transfer. Progress in demonstrating the scalability of this approach, as well as the environmental stability of ALD/ALE Al mirrors are discussed in the context of possible future applications for NASA LUVOIR and HabEx mission concepts.
Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; De Rossi, Pietro; Angeletti, Gloria; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo
2015-12-01
Several studies reported that hypnosis can modulate pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. We conducted an Activation Likelihood Estimation (ALE) meta-analysis on functional neuroimaging studies of pain perception under hypnosis to identify brain activation-deactivation patterns occurring during hypnotic suggestions aiming at pain reduction, including hypnotic analgesic, pleasant, or depersonalization suggestions (HASs). We searched the PubMed, Embase and PsycInfo databases; we included papers published in peer-reviewed journals dealing with functional neuroimaging and hypnosis-modulated pain perception. The ALE meta-analysis encompassed data from 75 healthy volunteers reported in 8 functional neuroimaging studies. HASs during experimentally-induced pain compared to control conditions correlated with significant activations of the right anterior cingulate cortex (Brodmann's Area [BA] 32), left superior frontal gyrus (BA 6), and right insula, and deactivation of right midline nuclei of the thalamus. HASs during experimental pain impact both cortical and subcortical brain activity. The anterior cingulate, left superior frontal, and right insular cortices activation increases could induce a thalamic deactivation (top-down inhibition), which may correlate with reductions in pain intensity. Copyright © 2016 Elsevier Ltd. All rights reserved.
ALE3D Simulation and Measurement of Violence in a Fast Cookoff Experiment with LX-10
DOE Office of Scientific and Technical Information (OSTI.GOV)
McClelland, M A; Maienschein, J L; Howard, W M
We performed a computational and experimental analysis of fast cookoff of LX-10 (94.7% HMX, 5.3% Viton A) confined in a 2 kbar steel tube with reinforced end caps. A Scaled-Thermal-Explosion-eXperiment (STEX) was completed in which three radiant heaters were used to heat the vessel until ignition, resulting in a moderately violent explosion after 20.4 minutes. Thermocouple measurements showed tube temperatures as high as 340 C at ignition and LX-10 surface temperatures as high as 279 C, which is near the melting point of HMX. Three micro-power radar systems were used to measure mean fragment velocities of 840 m/s. Photonics Dopplermore » Velocimeters (PDVs) showed a rapid acceleration of fragments over 80 {micro}s. A one-dimensional ALE3D cookoff model at the vessel midplane was used to simulate the heating, thermal expansion, LX-10 decomposition composition, and closing of the gap between the HE (High Explosive) and vessel wall. Although the ALE3D simulation terminated before ignition, the model provided a good representation of heat transfer through the case and across the dynamic gap to the explosive.« less
Validation of Air-Backed Underwater Explosion Experiments with ALE3D
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leininger, L D
2005-02-04
This paper summarizes an exercise carried out to validate the process of implementing LLNL's ALE3D to predict the permanent deformation and rupture of an air-backed steel plate subjected to underwater shock. Experiments were performed in a shock tank at the Naval Science and Technology Laboratory in Visakhapatnam India, and the results are documented in reference. A consistent set of air-backed plates is subjected to shocks from increasing weights of explosives ranging from 10g-80g. At 40g and above, rupture is recorded in the experiment and, without fracture mechanics implemented in ALE3D, only the cases of 10g, 20g, and 30g are presentedmore » here. This methodology applies the Jones-Wilkins-Lee (JWL) Equation of State (EOS) to predict the pressure of the expanding detonation products, the Gruneisein EOS for water under highly dynamic compressible flow - both on 1-point integrated 3-d continuum elements. The steel plates apply a bilinear elastic-plastic response with failure and are simulated with 3-point integrated shell elements. The failure for this exercise is based on effective (or equivalent) plastic strain.« less
A Meta-Analytic Study of the Neural Systems for Auditory Processing of Lexical Tones.
Kwok, Veronica P Y; Dan, Guo; Yakpo, Kofi; Matthews, Stephen; Fox, Peter T; Li, Ping; Tan, Li-Hai
2017-01-01
The neural systems of lexical tone processing have been studied for many years. However, previous findings have been mixed with regard to the hemispheric specialization for the perception of linguistic pitch patterns in native speakers of tonal language. In this study, we performed two activation likelihood estimation (ALE) meta-analyses, one on neuroimaging studies of auditory processing of lexical tones in tonal languages (17 studies), and the other on auditory processing of lexical information in non-tonal languages as a control analysis for comparison (15 studies). The lexical tone ALE analysis showed significant brain activations in bilateral inferior prefrontal regions, bilateral superior temporal regions and the right caudate, while the control ALE analysis showed significant cortical activity in the left inferior frontal gyrus and left temporo-parietal regions. However, we failed to obtain significant differences from the contrast analysis between two auditory conditions, which might be caused by the limited number of studies available for comparison. Although the current study lacks evidence to argue for a lexical tone specific activation pattern, our results provide clues and directions for future investigations on this topic, more sophisticated methods are needed to explore this question in more depth as well.
A Meta-Analytic Study of the Neural Systems for Auditory Processing of Lexical Tones
Kwok, Veronica P. Y.; Dan, Guo; Yakpo, Kofi; Matthews, Stephen; Fox, Peter T.; Li, Ping; Tan, Li-Hai
2017-01-01
The neural systems of lexical tone processing have been studied for many years. However, previous findings have been mixed with regard to the hemispheric specialization for the perception of linguistic pitch patterns in native speakers of tonal language. In this study, we performed two activation likelihood estimation (ALE) meta-analyses, one on neuroimaging studies of auditory processing of lexical tones in tonal languages (17 studies), and the other on auditory processing of lexical information in non-tonal languages as a control analysis for comparison (15 studies). The lexical tone ALE analysis showed significant brain activations in bilateral inferior prefrontal regions, bilateral superior temporal regions and the right caudate, while the control ALE analysis showed significant cortical activity in the left inferior frontal gyrus and left temporo-parietal regions. However, we failed to obtain significant differences from the contrast analysis between two auditory conditions, which might be caused by the limited number of studies available for comparison. Although the current study lacks evidence to argue for a lexical tone specific activation pattern, our results provide clues and directions for future investigations on this topic, more sophisticated methods are needed to explore this question in more depth as well. PMID:28798670
Neuropathic orofacial pain: Facts and fiction.
Baad-Hansen, Lene; Benoliel, Rafael
2017-06-01
Definition and taxonomy This review deals with neuropathic pain of traumatic origin affecting the trigeminal nerve, i.e. painful post-traumatic trigeminal neuropathy (PTTN). Symptomatology The clinical characteristics of PTTN vary considerably, partly due to the type and extent of injury. Symptoms involve combinations of spontaneous and evoked pain and of positive and negative somatosensory signs. These patients are at risk of going through unnecessary dental/surgical procedures in the attempt to eradicate the cause of the pain, due to the fact that most dentists only rarely encounter PTTN. Epidemiology Overall, approximately 3% of patients with trigeminal nerve injuries develop PTTN. Patients are most often female above the age of 45 years, and both physical and psychological comorbidities are common. Pathophysiology PTTN shares many pathophysiological mechanisms with other peripheral neuropathic pain conditions. Diagnostic considerations PTTN may be confused with one of the regional neuralgias or other orofacial pain conditions. For intraoral PTTN, early stages are often misdiagnosed as odontogenic pain. Pain management Management of PTTN generally follows recommendations for peripheral neuropathic pain. Expert opinion International consensus on classification and taxonomy is urgently needed in order to advance the field related to this condition.
Shah, Ameer T; Dagher, Walid I; O'Leary, Miriam A; Wein, Richard O
The differential diagnosis of facial anesthesia is vast. This may be secondary to trauma, neoplasm, both intracranial and extracranial, infection, and neurologic disease. When evaluating a patient with isolated facial anesthesia, the head and neck surgeon often thinks of adenoid cystic carcinoma, which has a propensity for perineural invasion and spread. When one thinks of head and neck squamous cell carcinoma with or without unknown primary, the typical presentation involves dysphagia, odynophagia, weight loss, hoarseness, or more commonly, a neck mass. Squamous cell carcinoma presenting as facial anesthesia and perineural spread, with no primary site is quite rare. Case presentations and review of the literature. Trigeminal anesthesia is an uncommon presentation of head and neck squamous cell carcinoma with unknown primary. We present two interesting cases of invasive squamous cell carcinoma of the trigeminal nerve, with no primary site identified. We will also review the literature of head and neck malignancies with perineural spread and the management techniques for the two different cases presented. Copyright © 2016 Elsevier Inc. All rights reserved.
Ohmoto, Makoto; Matsumoto, Ichiro; Yasuoka, Akihito; Yoshihara, Yoshihiro; Abe, Keiko
2008-08-01
We established transgenic mouse lines expressing a transneuronal tracer, wheat germ agglutinin (WGA), under the control of mouse T1R3 gene promoter/enhancer. In the taste buds, WGA transgene was faithfully expressed in T1R3-positive sweet/umami taste receptor cells. WGA protein was transferred not laterally to the synapse-bearing, sour-responsive type III cells in the taste buds but directly to a subset of neurons in the geniculate and nodose/petrosal ganglia, and further conveyed to a rostro-central region of the nucleus of solitary tract. In addition, WGA was expressed in solitary chemoreceptor cells in the nasal epithelium and transferred along the trigeminal sensory pathway to the brainstem neurons. The solitary chemoreceptor cells endogenously expressed T1R3 together with bitter taste receptors T2Rs. This result shows an exceptional signature of receptor expression. Thus, the t1r3-WGA transgenic mice revealed the sweet/umami gustatory pathways from taste receptor cells and the trigeminal neural pathway from solitary chemoreceptor cells.
On the nature of the afferent fibers of oculomotor nerve.
Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L
1989-03-01
The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve.
Diversity amongst trigeminal neurons revealed by high throughput single cell sequencing
Nguyen, Minh Q.; Wu, Youmei; Bonilla, Lauren S.; von Buchholtz, Lars J.
2017-01-01
The trigeminal ganglion contains somatosensory neurons that detect a range of thermal, mechanical and chemical cues and innervate unique sensory compartments in the head and neck including the eyes, nose, mouth, meninges and vibrissae. We used single-cell sequencing and in situ hybridization to examine the cellular diversity of the trigeminal ganglion in mice, defining thirteen clusters of neurons. We show that clusters are well conserved in dorsal root ganglia suggesting they represent distinct functional classes of somatosensory neurons and not specialization associated with their sensory targets. Notably, functionally important genes (e.g. the mechanosensory channel Piezo2 and the capsaicin gated ion channel Trpv1) segregate into multiple clusters and often are expressed in subsets of cells within a cluster. Therefore, the 13 genetically-defined classes are likely to be physiologically heterogeneous rather than highly parallel (i.e., redundant) lines of sensory input. Our analysis harnesses the power of single-cell sequencing to provide a unique platform for in silico expression profiling that complements other approaches linking gene-expression with function and exposes unexpected diversity in the somatosensory system. PMID:28957441
Glial pannexin1 contributes to tactile hypersensitivity in a mouse model of orofacial pain
Hanstein, Regina; Hanani, Menachem; Scemes, Eliana; Spray, David C.
2016-01-01
Drug studies in animal models have implicated pannexin1 (Panx1) in various types of pain, including trigeminal hypersensitivity, neuropathic pain and migraine. However, the tested drugs have limited specificity and efficacy so that direct evidence for Panx1 contribution to pain has been lacking. We here show that tactile hypersensitivity is markedly attenuated by deletion of Panx1 in a mouse model of chronic orofacial pain; in this model, trigeminal ganglion Panx1 expression and function are markedly enhanced. Targeted deletion of Panx1 in GFAP-positive glia or in neurons revealed distinct effects. Panx1 deletion in GFAP-positive glia cells prevented hypersensitivity completely, whereas deletion of neuronal Panx1 reduced baseline sensitivity and the duration of hypersensitivity. In trigeminal ganglia with genetically encoded Ca2+ indicator in GFAP-positive glia or in neurons, both cell populations were found to be hyperactive and hyper-responsive to ATP. These novel findings reveal unique roles for GFAP-positive glial and neuronal Panx1 and describe new chronic pain targets for cell-type specific intervention in this often intractable disease. PMID:27910899
NASA Astrophysics Data System (ADS)
Chen, Hui-Ming; Wu, Ming-Tsang
2017-01-01
Groundwater pollution from the petrochemical industry causes serious deterioration of soil and groundwater quality and impacts on human health worldwide. However, few studies have examined the effect of residential exposure to petrochemical chlorinated hydrocarbon-contaminated groundwater on renal function impairment in humans. We conducted an ecological study to investigate the two. A polyvinyl chloride (PVC) plant was located in one of the six villages, the study area, in Kaohsiung city of southwestern Taiwan. Based on the direction of groundwater flow and previous groundwater measurements of chlorinated hydrocarbons from Taiwan Environmental Protection Bureau, we divided the six villages into highly-polluted villages, moderately-polluted villages, and a non-polluted village. All inhabitants in those six villages were invited to receive free health examinations between May-June, 2010. In total, 4,432 study subjects ≥18 yrs old were analyzed. Compared to those in the non-polluted village, subjects in highly-polluted villages had 1.89- and 1.46-fold the risk of impaired estimated glomerular filtration rate (eGFR) and proteinuria (95% CI = 1.15-1.85 and 1.09-3.28, respectively) after adjusting for other covariates. Given this relative large sample size, we found that groundwater chlorinated hydrocarbon pollution can cause kidney damage in adults.
Zaytsev, A Yu; Nazaryan, D N; Kim, S Yu; Dubrovin, K V; Svetlov, V A; Khovrin, V V
2014-01-01
There are difficulties in procedure of regional block of 2 and 3 brunches of the trigeminal nerve despite availability of many different methods of nerves imaging. The difficulties are connected with complex anatomy structure. Neurostimulation not always effective and as a rule, is accompanied with wrong interpretation of movement response on stimulation. The changing of the tactics on paraesthesia search improves the situation. The use of new methods of nerves imaging (3D-CT) also allows decreasing the frequency of fails during procedure of regional block of the brunches of the trigeminal nerve.
Episodic Dural Stimulation in Awake Rats: A Model for Recurrent Headache
Oshinsky, Michael L.; Gomonchareonsiri, Sumittra
2014-01-01
Objectives To model, in rats, the development of chronic trigeminal nociceptive hypersensitivity seen in patients with recurrent headache. Background Pathophysiology studies suggest that patients with recurrent migraine headache experience repeated bouts of dural nociceptor activation. In some patients, the severity and frequency of headache attacks increase over time. Patients with recurrent headache are hypersensitive to nitric oxide donors, such as glyceryl trinitrate (GTN). Current trigeminal pain models do not reflect the repeated episodic nature of dural nociceptor activation in patients with recurrent headache. Repeated nociceptor activation creates long-lasting changes in the periphery and brain due to activity-dependent neuronal plasticity. An animal model of repeated activation of dural nociceptors will facilitate the study of the physiological changes caused by repeated, episodic pain and the factors important for the transition of episodic to chronic migraine. Methods We induced dural inflammation by infusing an inflammatory soup (IS) through a cannula on the dura in awake behaving rats. This was repeated 3 times per week for up to 4 weeks. Periorbital pressure sensory testing was used to monitor the change in trigeminal sensitivity. Rats were challenged with GTN to test the hypothesis that many dural stimulations are required to model the hypersensitivity of migraine patients. Quantitative trigeminal sensory testing and microdialysis in the trigeminal nucleus caudalis (TNC) were used to measure GTN hypersensitivity. Results Multiple infusions of IS (>8), over weeks, induced a long-lasting decrease in periorbital pressure thresholds that lasted >3 weeks after the last infusion. In contrast, IS infusion in IS-naive rats and those that received 3 IS infusions produced only short-lasting decreases in periorbital pressure thresholds. Rats that received more than 8 IS infusions showed a marked increase in their neurochemical and behavioral responses to GTN. In these rats, GTN induced a decrease in periorbital von Frey thresholds that lasted >5 hours. In contrast, in rats that received only 3 IS infusions, GTN caused a threshold decrease for 1.5 hour. In vivo microdialysis in the TNC showed that GTN increased extracellular glutamate levels in rats with more than 8 IS infusions to 7.7 times the basal levels. In IS-naive rats and those that received only 3 IS infusions, the extracellular glutamate levels rose to only 1.7 and 1.9 times the basal level, respectively. Conclusions Repeated IS stimulation of the dura produces a chronic state of trigeminal hypersensitivity and potentiates the response to GTN. This hyperresponsiveness outlasts the last IS infusion and is the basis of our rat model of recurrent headache. This model can be used to study the changes in the brain and periphery induced by repeated trigeminovascular nociceptor activation and has the potential to elucidate the mechanisms for the transition of episodic to chronic headache. PMID:17635594
Kramer, P. R.; Bellinger, L. L.
2013-01-01
Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabrα6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabrα6 role in myofascial pain we hypothesized that Gabrα6 has an inhibitory role in myofascial nociceptive responses similar to inflammatory TMJ arthritis. To test this hypothesis a, myofascial nociceptive response was induced by placing a ligature bilaterally on the tendon attachment of the anterior superficial part of a male rat's masseter muscle. Four days after ligature placement Gabrα6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabra6 siRNA) or no known gene (control siRNA). After siRNA infusion nociceptive behavioral responses were measured, i.e., feeding behavior and head withdrawal after pressing upon the region above the ligature with von Frey filaments. Neuronal activity in the TG and trigeminal nucleus caudalis and upper cervical region (Vc–C1) was measured by quantitating the amount of phosphorylated extracellular signalregulated kinase (p-ERK). Total Gabrα6 and GABAA receptor contents in the TG and Vc–C1 were determined. Gabrα6 siRNA infusion reduced Gabrα6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabra6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabrα6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception. PMID:23602886
Sokolov, A Y; Lyubashina, O A; Berkovich, R R; Panteleev, S S
2015-09-01
Migraine is a chronic neurological disorder characterized by episodes of throbbing headaches. Practically all medications currently used in migraine prophylaxis have a number of substantial disadvantages and use limitations. Therefore, the further search for principally new prophylactic antimigraine agents remains an important task. The objective of our study was to evaluate the effects of a fixed combination of dextromethorphan hydrobromide and quinidine sulphate (DM/Q) on activity of the spinal trigeminal neurons in an electrophysiological model of trigemino-durovascular nociception. The study was performed in 15 male Wistar rats, which were anaesthetized with urethane/α-chloralose and paralysed using pipecuronium bromide. The effects of cumulative intravenous infusions of DM/Q (three steps performed 30 min apart, 15/7.5 mg/kg of DM/Q in 0.5 mL of isotonic saline per step) on ongoing and dural electrical stimulation-induced neuronal activities were tested in a group of eight rats over 90 min. Other seven animals received cumulative infusion of equal volumes of saline and served as control. Cumulative administration of DM/Q produced steady suppression of both the ongoing activity of the spinal trigeminal neurons and their responses to electrical stimulation of the dura mater. It is evident that the observed DM/Q-induced suppression of trigeminal neuron excitability can lead to a reduction in nociceptive transmission from meninges to higher centres of the brain. Since the same mechanism is believed to underlie the pharmacodynamics of many well-known antimigraine drugs, results of the present study enable us to anticipate the potential efficacy of DM/Q in migraine. © 2014 European Pain Federation - EFIC®
Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam
2016-04-01
It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.
Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.
Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale
2018-04-01
To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.
Lin, Bo; Lu, Xuguang; Zhai, Xinli; Cai, Zhigang
2014-12-01
The objective of this study was to develop an electrophysiological method for intraoperative localization of the trigeminal nerve branches during radiofrequency thermocoagulation (RFTC). Twenty-three patients who were scheduled to undergo RFTC were included. The trigeminal nerve root was stimulated through the foramen ovale using the radiofrequency cannula. Antidromic responses were recorded from the target division through supraorbital, infraorbital, and mental foramina electrodes, and an additional electrode at the masseter muscle. Sensory and motor action responses, as well as verbal and masseter contraction responses, were recorded and correlated. The antidromic responses were easily recorded in the target division in all 23 patients, and they were invariably correlated with the patient's verbal responses. The potentials were recorded successively from V1 to V3. The amplitude in each division before and after RFTC showed little difference in response to electrical stimulation with the same current. The motor trigeminal nerve action potentials were recorded in 10 patients; 7 of these patients had postoperative masseter muscle weakness, while the remaining 3 had normal masseter muscle function. Potentials with low amplitudes were usually obtained from neighboring divisions, but no unexpected denervation of any branches was observed. All the patients experienced immediate pain relief after the procedure. This technique is sensitive and easy to apply. The sensory and motor potentials matched the verbal responses and the complications. Although it cannot completely substitute for the patient's verbal response, this approach is helpful in uncooperative patients, and it predicts and reduces the incidence of masseter muscle weakness. The use of these complementary techniques could increase the chances of treatment success.
Khatibi, Kasra; Choudhri, Omar; Connolly, Ian D; McTaggart, Ryan A; Do, Huy M
2017-02-01
Trigeminal-cardiac reflex (TCR) from the stimulation of sensory branches of trigeminal nerve can lead to hemodynamic instability. This phenomenon has been described during ophthalmologic, craniofacial, and skull base surgeries. TCR has been reported rarely with endovascular onyx embolization of dural arteriovenous fistulas. We report a case of TCR during endovascular Onyx embolization of an arteriovenous malformation (AVM). A 16-year-old boy presented with a large cerebellar AVM with arterial feeders from the external carotid artery and posterior cerebral artery branches. The middle meningeal artery was catheterized, through which dimethyl sulfoxide was injected, followed by Onyx, into the nidus and the feeders. Near the completion of embolization, patient became bradycardic and proceeded to asystole; he was resuscitated with chest compression, atropine, and vasopressors. We used PubMed to identify the reported cases of Onyx and other endovascular embolizations complicated by hemodynamic instability. We found 16 cases of endovascular onyx embolization complicated by clinically significant hemodynamic changes in the treatment of dural arteriovenous fistula, cavernous carotid fistula, and juvenile nasopharygeal angiofibroma but not with AVMs. In these cases, arterial supply to the nidus involved the sensory receptive field of trigeminal nerve. Hemodynamic changes have been reported during the injection of dimethyl sulfoxide before the introduction of Onyx, as well as Onyx injection and cast formation. TCR can lead to significant hemodynamic changes during endovascular Onyx embolization of vascular malformations (both pial AVM and dural arteriovenous fistulas) involving receptive field of trigeminal nerve. Therefore, the anesthesiologist should be made aware of treatment approach before intervention and appropriate precautions taken. Copyright © 2016 Elsevier Inc. All rights reserved.
Mameli, Ombretta; Caria, Marcello A; Biagi, Francesca; Zedda, Marco; Farina, Vittorio
2017-05-01
It has been recently shown in rats that spontaneous movements of whisker pad macrovibrissae elicited evoked responses in the trigeminal mesencephalic nucleus (Me5). In the present study, electrophysiological and neuroanatomical experiments were performed in anesthetized rats to evaluate whether, besides the whisker displacement per se, the Me5 neurons are also involved in encoding the kinematic properties of macrovibrissae movements, and also whether, as reported for the trigeminal ganglion, even within the Me5 nucleus exists a neuroanatomical representation of the whisker pad macrovibrissae. Extracellular electrical activity of single Me5 neurons was recorded before, during, and after mechanical deflection of the ipsilateral whisker pad macrovibrissae in different directions, and with different velocities and amplitudes. In several groups of animals, single or multiple injections of the tracer Dil were performed into the whisker pad of one side, in close proximity to the vibrissae follicles, in order to label the peripheral terminals of the Me5 neurons innervating the macrovibrissae (whisking-neurons), and therefore, the respective perikaria within the nucleus. Results showed that: (1) the whisker pad macrovibrissae were represented in the medial-caudal part of the Me5 nucleus by a single cluster of cells whose number seemed to match that of the macrovibrissae; (2) macrovibrissae mechanical deflection elicited significant responses in the Me5 whisking-neurons, which were related to the direction, amplitude, and frequency of the applied deflection. The specific functional role of Me5 neurons involved in encoding proprioceptive information arising from the macrovibrissae movements is discussed within the framework of the whole trigeminal nuclei activities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons.
Han, Jin-Eon; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung
2017-03-01
The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K + and Ca 2+ channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K + currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K + currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs + (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca 2+ channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.
Marinelli, John P; Van Gompel, Jamie J; Link, Michael J; Carlson, Matthew L
2018-05-01
Secondary trigeminal neuralgia (TN) is uncommon. When a space-occupying lesion with mass effect is identified, the associated TN is often exclusively attributed to the tumor. This report illustrates the importance of considering coexistent actionable pathology when surgically treating secondary TN. A 51-year-old woman presented with abrupt-onset TN of the V2 and V3 nerve divisions with hypesthesia. She denied changes in hearing, balance, or facial nerve dysfunction. Magnetic resonance imaging revealed a 1.6-cm contrast-enhancing cerebellopontine angle tumor that effaced the trigeminal nerve, consistent with a vestibular schwannoma. In addition, a branch of the superior cerebellar artery abutted the cisternal segment of the trigeminal nerve on T2-weighted thin-slice magnetic resonance imaging. Intraoperative electrical stimulation of the tumor elicited a response from the facial nerve at low threshold over the entire accessible tumor surface, indicating that the tumor was a facial nerve schwannoma. Considering the patient's lack of facial nerve deficit and that the tumor exhibited no safe entry point for intracapsular debulking, tumor resection was not performed. Working between the tumor and tentorium, a branch of the superior cerebellar artery was identified and decompressed with a Teflon pad. At last follow-up, the patient exhibited resolution of her TN. Her hearing and facial nerve function remained intact. Despite obstruction from a medium-sized tumor, it is still possible to achieve microvascular decompression of the fifth cranial nerve. This emphasizes the importance of considering other actionable pathology during surgical management of presumed tumor-induced TN. Further, TN is relatively uncommon with medium-sized vestibular schwannomas and coexistent causes should be considered. Copyright © 2018 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dhople, Anil; Kwok, Young; Chin, Lawrence
2007-10-01
Purpose: To assess efficacy and quality of life (QOL) outcomes associated with gamma-knife radiosurgery (GK-RS) in treating atypical trigeminal neuralgia (ATN) compared with classic trigeminal neuralgia (CTN). Methods and Materials: Between September 1996 and September 2004, 35 cases of ATN were treated with GK-RS. Patients were categorized into two groups: Group I comprised patients presenting with ATN (57%); Group II consisted of patients presenting with CTN then progressing to ATN (43%). Median prescription dose 75 Gy (range, 70-80 Gy) was delivered to trigeminal nerve root entry zone. Treatment efficacy and QOL improvements were assessed with a standardized questionnaire. Results: Withmore » median follow-up of 29 months (range, 3-74 months), 72% reported excellent/good outcomes, with mean time to relief of 5.8 weeks (range, 0-24 weeks) and mean duration of relief of 62 weeks (range, 1-163 weeks). This rate of pain relief is similar to rate achieved in our previously reported experience treating CTN with GK-RS (p = 0.36). There was a trend toward longer time to relief (p = 0.059), and shorter duration of relief (p = 0.067) in patients with ATN. There was no difference in rate of, time to, or duration of pain relief between Groups I and II. Of the patients with ATN, 88% discontinued or decreased the use of pain medications. Among the patients with sustained pain relief, QOL improved an average of 85%. Conclusion: This is the largest reported GK-RS experience for the treatment of ATN. Patients with ATN can achieve rates of pain relief similar to those in patients with CTN. Further follow-up is necessary to assess adequately the durability of response.« less
Long-Term Outcome of Gamma Knife Radiosurgery for Treatment of Typical Trigeminal Neuralgia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Han, Jung Ho; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.k; Chung, Hyun-Tai
2009-11-01
Purpose: To analyze the long-term outcomes of patients with typical trigeminal neuralgia treated with gamma knife radiosurgery (GKRS). Patients and Methods: A total of 62 consecutive patients with typical trigeminal neuralgia were treated with GKRS between 1998 and 2004. Of the 62 patients, 2 were lost to follow-up; the remaining 60 patients were followed for >12 months. The mean prescribed maximal dose was 79.7 Gy (range, 75-80), using a 4-mm shot. Results: Of the 60 patients, 48 were followed for >4 years. An additional 3 patients, followed for <4 years, experienced recurrent pain after a favorable initial response and weremore » incorporated into the long-term response analysis. Of these 51 patients (mean age, 61 +- 11 years; 37 women [72.5%]; and mean follow-up duration, 58 +- 14 months), 46 (90.2%) responded to GKRS, as demonstrated by an improvement in their Barrow Neurological Institute pain intensity score. Of the 46 patients, 24 (52.2%) had pain recurrence. The actuarial recurrence-free survival rate was 84.8%, 76.1%, 69.6%, 63.0%, and 45.8% at 1, 2, 3, 4, and 5 years after radiosurgery, respectively. Patient age >70 years correlated with a favorable outcome in terms of pain recurrence after radiosurgery (hazard ratio, 0.125; 95% confidence interval, 0.016-0.975; p = .047) on multivariate analysis. Conclusion: GKRS seems to be an effective treatment modality for patients with typical trigeminal neuralgia considering the initial response rate; however, fewer than one-half of patients might continue to benefit from GKRS after long-term follow-up. Elderly patients might be good candidates for radiosurgery considering the long-term durability of efficacy.« less
Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aubuchon, Adam C., E-mail: acaubuchon@gmail.com; Chan, Michael D.; Lovato, James F.
2011-11-15
Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90).more » The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.« less
Boucher, Yves; Moreau, Nathan; Mauborgne, Annie; Dieb, Wisam
2018-06-18
We explored the molecular and behavioral effects of a perineural Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN. Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early pain-like behavior (i.e. an increase in spontaneous pain [SP] or mechanical static allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory cytokine Interleukin 1 beta (IL - 1β) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1β/iNOS-dependent central sensitization mechanisms. Copyright © 2018. Published by Elsevier Inc.
2012-01-01
Background Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. Results KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. Conclusions Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons. PMID:23171280
Manteniotis, Stavros; Lehmann, Ramona; Flegel, Caroline; Vogel, Felix; Hofreuter, Adrian; Schreiner, Benjamin S. P.; Altmüller, Janine; Becker, Christian; Schöbel, Nicole; Hatt, Hanns; Gisselmann, Günter
2013-01-01
The specific functions of sensory systems depend on the tissue-specific expression of genes that code for molecular sensor proteins that are necessary for stimulus detection and membrane signaling. Using the Next Generation Sequencing technique (RNA-Seq), we analyzed the complete transcriptome of the trigeminal ganglia (TG) and dorsal root ganglia (DRG) of adult mice. Focusing on genes with an expression level higher than 1 FPKM (fragments per kilobase of transcript per million mapped reads), we detected the expression of 12984 genes in the TG and 13195 in the DRG. To analyze the specific gene expression patterns of the peripheral neuronal tissues, we compared their gene expression profiles with that of the liver, brain, olfactory epithelium, and skeletal muscle. The transcriptome data of the TG and DRG were scanned for virtually all known G-protein-coupled receptors (GPCRs) as well as for ion channels. The expression profile was ranked with regard to the level and specificity for the TG. In total, we detected 106 non-olfactory GPCRs and 33 ion channels that had not been previously described as expressed in the TG. To validate the RNA-Seq data, in situ hybridization experiments were performed for several of the newly detected transcripts. To identify differences in expression profiles between the sensory ganglia, the RNA-Seq data of the TG and DRG were compared. Among the differentially expressed genes (> 1 FPKM), 65 and 117 were expressed at least 10-fold higher in the TG and DRG, respectively. Our transcriptome analysis allows a comprehensive overview of all ion channels and G protein-coupled receptors that are expressed in trigeminal ganglia and provides additional approaches for the investigation of trigeminal sensing as well as for the physiological and pathophysiological mechanisms of pain. PMID:24260241
Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M; Helfand, Helen; Aicher, Sue A
2010-09-01
Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene-related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple-labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations.
Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren
2009-01-01
Expression of the N-methyl-d-aspartate (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor-kappa B (NF-kappaB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50mul of complete Freund's adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on days 1, 3, and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-kappaB on days 3 and 7, and of IL-6 on days 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-kappaB inhibitor (PDTC) for 6 days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for 6 days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-kappaB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats.
Toward Improved Fidelity of Thermal Explosion Simulations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nichols, A L; Becker, R; Howard, W M
2009-07-17
We will present results of an effort to improve the thermal/chemical/mechanical modeling of HMX based explosive like LX04 and LX10 for thermal cook-off. The original HMX model and analysis scheme were developed by Yoh et.al. for use in the ALE3D modeling framework. The current results were built to remedy the deficiencies of that original model. We concentrated our efforts in four areas. The first area was addition of porosity to the chemical material model framework in ALE3D that is used to model the HMX explosive formulation. This is needed to handle the roughly 2% porosity in solid explosives. The secondmore » area was the improvement of the HMX reaction network, which included the inclusion of a reactive phase change model base on work by Henson et.al. The third area required adding early decomposition gas species to the CHEETAH material database to develop more accurate equations of state for gaseous intermediates and products. Finally, it was necessary to improve the implicit mechanics module in ALE3D to more naturally handle the long time scales associated with thermal cook-off. The application of the resulting framework to the analysis of the Scaled Thermal Explosion (STEX) experiments will be discussed.« less
NASA Astrophysics Data System (ADS)
Wang, Ye; Cai, Jiejin; Li, Qiong; Yin, Huaqiang; Yang, Xingtuan
2018-06-01
Gas-liquid two phase flow exists in several industrial processes and light-water reactors (LWRs). A diffuse interface based finite element method with two different mesh generation methods namely, the Adaptive Mesh Refinement (AMR) and the Arbitrary Lagrange Euler (ALE) methods is used to model the shape and velocity changes in a rising bubble. Moreover, the calculating speed and mesh generation strategies of AMR and ALE are contrasted. The simulation results agree with the Bhagat's experiments, indicating that both mesh generation methods can simulate the characteristics of bubble accurately. We concluded that: the small bubble rises as elliptical with oscillation, whereas a larger bubble (11 mm > d > 7 mm) rises with a morphology between the elliptical and cap type with a larger oscillation. When the bubble is large (d > 11 mm), it rises up as a cap type, and the amplitude becomes smaller. Moreover, it takes longer to achieve the stable shape from the ellipsoid to the spherical cap type with the increase of the bubble diameter. The results also show that for smaller diameter case, the ALE method uses fewer grids and has a faster calculation speed, but the AMR method can solve the case of a large geometry deformation efficiently.
Multi-Material ALE with AMR for Modeling Hot Plasmas and Cold Fragmenting Materials
NASA Astrophysics Data System (ADS)
Alice, Koniges; Nathan, Masters; Aaron, Fisher; David, Eder; Wangyi, Liu; Robert, Anderson; David, Benson; Andrea, Bertozzi
2015-02-01
We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian (ALE) hydrodynamics with Adaptive Mesh Refinement (AMR) to connect the continuum to the microstructural regimes. The code is unique in its ability to model hot radiating plasmas and cold fragmenting solids. New numerical techniques were developed for many of the physics packages to work efficiently on a dynamically moving and adapting mesh. We use interface reconstruction based on volume fractions of the material components within mixed zones and reconstruct interfaces as needed. This interface reconstruction model is also used for void coalescence and fragmentation. A flexible strength/failure framework allows for pluggable material models, which may require material history arrays to determine the level of accumulated damage or the evolving yield stress in J2 plasticity models. For some applications laser rays are propagating through a virtual composite mesh consisting of the finest resolution representation of the modeled space. A new 2nd order accurate diffusion solver has been implemented for the thermal conduction and radiation transport packages. One application area is the modeling of laser/target effects including debris/shrapnel generation. Other application areas include warm dense matter, EUV lithography, and material wall interactions for fusion devices.
Treatment strategy for trigeminal neuralgia: a thirty years experience.
Broggi, Giovanni; Ferroli, Paolo; Franzini, Angelo
2008-05-01
Trigeminal neuralgia is an invalidating disease when become drug-resistant. The only possible treatment is surgery with different modalities, percutaneous, open surgery or radiosurgery. The thirty years experience at the Fondazione Istituto Neurologico C. Besta, Milano, Italy suggests that these surgical strategies are successful in pain control in short and long term period in more than 90% of cases, with a low rate of side effects and high improvement of quality of life. The type of surgery should be tailored on the particular patient considering age, general physical condition, neuroradiological assessment in which MRI with dedicated sequences are mandatory, and also patient's attitude.
Mercante, Beniamina; Rangon, Claire-Marie
2018-01-01
Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions. PMID:29361732
Ma, AyeAye; Margolis, Mathew S.
2013-01-01
Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in different neuronal subtypes (A5+ and KH10+) in murine trigeminal ganglia, results which correlate with restricted productive infection in these neurons in vitro. HSV-2 latency-associated transcript (LAT) contains a cis-acting regulatory element near the transcription start site that promotes productive infection in A5+ neurons and a second element in exon 1 that inhibits productive infection in KH10+ neurons. HSV-1 contains no such regulatory sequences, demonstrating different mechanisms for regulating productive HSV infection in neurons. PMID:23514893
Evaluation and management of "sinus headache" in the otolaryngology practice.
Patel, Zara M; Setzen, Michael; Poetker, David M; DelGaudio, John M
2014-04-01
Patients, primary care doctors, neurologists and otolaryngologists often have differing views on what is truly causing headache in the sinonasal region. This review discusses common primary headache diagnoses that can masquerade as "sinus headache" or "rhinogenic headache," such as migraine, trigeminal neuralgia, tension-type headache, temporomandibular joint dysfunction, giant cell arteritis (also known as temporal arteritis) and medication overuse headache, as well as the trigeminal autonomic cephalalgias, including cluster headache, paroxysmal hemicrania, and hemicrania continua. Diagnostic criteria are discussed and evidence outlined that allows physicians to make better clinical diagnoses and point patients toward better treatment options. Copyright © 2014 Elsevier Inc. All rights reserved.
Latent Herpes Simplex Virus 1 Infection Does Not Induce Apoptosis in Human Trigeminal Ganglia
Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina
2015-01-01
Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8+ T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734
NASA Astrophysics Data System (ADS)
Pinheiro, Antonio L. B.; Marques, Aparecida Maria C.; Soares, Luiz Guiherme P.; de Carvalho, Fabiola B.; de Oliveira, Susana Carla P. S.; Cangussú, Maria Cristina T.
2017-02-01
Trigeminal neuralgia (TN) is a disabling syndrome and one of the most painful conditions that are often reported in female patients older than 50 years of age. The treatment generally includes drugs or surgical approaches. Laser Phototherapy -LPT has also been proposed as a safe and effective treatment modality. This work reports a series of patients of the Center of Biophotonics of the Federal University of Bahia (2000-2016) treated with LPT. Following standard anamneses, clinical and imaginologic examination and with the diagnosis of Trigeminal Neuralgia, the patients were set for light treatment. Treatment consisted of three sessions a week during six week. Prior irradiation, the patients were asked to score their pain using a VAS. λ780, λ 790, λ 830nm lasers were used on each session. Most patients were female (74.8%). At the end of the 12 sessions the patients were again examined and score their pain using VAS. No other intervention was carried out during the treatment. The results were statistically analyzed and showed that, the use of lower Energy Density in smaller number of session in younger patients presents higher effectivity on treating the pain on TN patients.
Orofacial complex regional pain syndrome: pathophysiologic mechanisms and functional MRI.
Lee, Yeon-Hee; Lee, Kyung Mi; Kim, Hyug-Gi; Kang, Soo-Kyung; Auh, Q-Schick; Hong, Jyung-Pyo; Chun, Yang-Hyun
2017-08-01
Complex regional pain syndrome (CRPS) is one of the most challenging chronic pain conditions and is characterized by burning pain, allodynia, hyperalgesia, autonomic changes, trophic changes, edema, and functional loss involving mainly the extremities. Until recently, very few reports have been published concerning CRPS involving the orofacial area. We report on a 50-year-old female patient who presented with unbearable pain in all of her teeth and hypersensitivity of the facial skin. She also reported intractable pain in both extremities accompanied by temperature changes and orofacial pain that increased when the other pains were aggravated. In the case of CRPS with trigeminal neuropathic pain, protocols for proper diagnosis and prompt treatment have yet to be established in academia or in the clinical field. We performed functional magnetic resonance imaging for a thorough analysis of the cortical representation of the affected orofacial area immediately before and immediately after isolated light stimulus of the affected hand and foot and concluded that CRPS can be correlated with trigeminal neuropathy in the orofacial area. Furthermore, the patient was treated with carbamazepine administration and stellate ganglion block, which can result in a rapid improvement of pain in the trigeminal region. Copyright © 2017 Elsevier Inc. All rights reserved.
Kaur, Rupinder; Rani, Pooja; Malhotra, Divye; Kaur, Rajwant; Dass, Praveen Kumar
2016-09-01
Reports of post herpetic maxillofacial complications have been very rarely documented in the literature that includes periapical lesions, calcified and devitalized pulps, resorption of roots, osteonecrosis, and spontaneous exfoliation of teeth. The atypical feature of the case of concern to the dental surgeon is the rare complication of spontaneous tooth exfoliation following herpes zoster. This case reports a male patient of age 47 years who reported to the Department of Periodontology with the chief complaint of mobility in the left upper central incisor. Patient history revealed herpes zoster infection that began 11 days earlier along with underlying diabetes mellitus condition. We hereby report a known diabetic patient with history of herpes zoster infection who presented with rare complication of spontaneous tooth exfoliation involving the maxillary division of the trigeminal nerve. Limited number of cases has been reported in the literature regarding spontaneous teeth exfoliation secondary to herpes zoster. The exact pathogenesis regarding the spontaneous exfoliation of teeth in herpes zoster patient is still controversial. Thus, an oral health care provider should be aware of this rare complication while managing a case of tooth mobility with the previous history of herpes zoster of trigeminal nerve.
Intranasal Localizability of Odorants: Influence of Stimulus Volume
Frasnelli, J.; Berg, J.; Huang, G.; Doty, R.L.
2011-01-01
When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicyclate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a “relatively pure” olfactory stimulus. PMID:21310764
Intranasal localizability of odorants: influence of stimulus volume.
Frasnelli, J; Hummel, T; Berg, J; Huang, G; Doty, R L
2011-05-01
When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicylate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a "relatively pure" olfactory stimulus.
Concurrent cervical and craniofacial pain. A review of empiric and basic science evidence.
Browne, P A; Clark, G T; Kuboki, T; Adachi, N Y
1998-12-01
Because many patients present themselves for treatment with both craniofacial and craniocervical pain, 2 questions arise: (1) What are the sensory and motor consequences of dysfunction in either of these areas on the other? (2) Do craniofacial and craniocervical pain have a similar cause? These questions formed the impetus for this review article. The phenomenon of concurrent pain in craniofacial and cervical structures is considered, and clinical reports and opinions are presented regarding theories of cervical-to-craniofacial and craniofacial-to-cervical pain referral. Because pain referral between these 2 areas requires anatomic and functional connectivity between trigeminally and cervically innervated structures, basic neurophysiologic and neuroanatomic literature is reviewed. The published data clearly demonstrate neurophysiologic and structural convergence of cervical sensory and muscle afferent inputs onto trigeminal subnucleus caudalis nociceptive and non-nociceptive neurons. Moreover, changes in metabolic activity and blood flow in the brainstem and cervical dorsal horn of the spinal cord in both monkeys and cats have been demonstrated after electric stimulation of the V1-innervated superior sagittal sinus. In conclusion, the animal experimental data support the findings of human empiric and experimental studies, which suggest that strong connectivity exists between trigeminal and cervical motor and sensory responses.
Pihut, M.; Szuta, M.; Ferendiuk, E.; Zeńczak-Więckiewicz, D.
2014-01-01
Chronic oral and facial pain syndromes are an indication for intervention of physicians of numerous medical specialties, while the complex nature of these complaints warrants interdisciplinary diagnostic and therapeutic approach. Oftentimes, lack of proper differentiation of pain associated with pathological changes of the surrounding tissues, neurogenic pain, vascular pain, or radiating pain from idiopathic facial pain leads to improper treatment. The objective of the paper is to provide detailed characterization of pain developing in the natural history of trigeminal neuralgia and temporomandibular joint dysfunction, with particular focus on similarities accounting for the difficulties in diagnosis and treatment as well as on differences between both types of pain. It might seem that trigeminal neuralgia can be easily differentiated from temporomandibular joint dysfunction due to the acute, piercing, and stabbing nature of neuralgic pain occurring at a single facial location to spread along the course of the nerve on one side, sometimes a dozen or so times a day, without forewarning periods. Both forms differ significantly in the character and intensity of pain. The exact analysis of the nature, intensity, and duration of pain may be crucial for the differential diagnostics of the disorders of our interest. PMID:24995309
Vit, Jean-Philippe; Ohara, Peter T; Bhargava, Aditi; Kelley, Kanwar; Jasmin, Luc
2008-04-16
Growing evidence suggests that changes in the ion buffering capacity of glial cells can give rise to neuropathic pain. In the CNS, potassium ion (K+) buffering is dependent on the glia-specific inward rectifying K+ channel Kir4.1. We recently reported that the satellite glial cells that surround primary sensory neurons located in sensory ganglia of the peripheral nervous system also express Kir4.1, whereas the neurons do not. In the present study, we show that, in the rat trigeminal ganglion, the location of the primary sensory neurons for face sensation, specific silencing of Kir4.1 using RNA interference leads to spontaneous and evoked facial pain-like behavior in freely moving rats. We also show that Kir4.1 in the trigeminal ganglion is reduced after chronic constriction injury of the infraorbital nerve. These findings suggests that neuropathic pain can result from a change in expression of a single K+ channel in peripheral glial cells, raising the possibility of targeting Kir4.1 to treat pain in general and particularly neuropathic pain that occurs in the absence of nerve injury.
Vit, Jean-Philippe; Ohara, Peter T.; Bhargava, Aditi; Kelley, Kanwar; Jasmin, Luc
2008-01-01
Growing evidence suggests that changes in the ion buffering capacity of glial cells can give rise to neuropathic pain. In the CNS, potassium ion (K+) buffering is dependent on the glia-specific inward rectifying K+ channel Kir4.1. We recently reported that the satellite glial cells (SGCs) that surround primary sensory neurons located in sensory ganglia of the peripheral nervous system also express Kir4.1 while the neurons do not. In the present study we show that in the rat trigeminal ganglion, the location of the primary sensory neurons for face sensation, specific silencing of Kir4.1 using RNA interference leads to spontaneous and evoked facial pain-like behavior in freely moving rats. We also show that Kir4.1 in the trigeminal ganglion is reduced following chronic constriction injury of the infraorbital nerve. These findings suggests that neuropathic pain can result from a change in expression of a single K+ channel in peripheral glial cells, raising the possibility of targeting Kir4.1 to treat pain in general, and particularly neuropathic pain that occurs in the absence of nerve injury. PMID:18417695
2014-01-01
Background The guidelines on trigeminal neuralgia management that have been agreed and jointly published by the American Academy of Neurology and the European Federation of Neurological Societies recommend carbamazepine (CBZ) and oxcarbazepine (OXC) as the first-choice medical treatments in patients with trigeminal neuralgia (TN). The aim of this retrospective study was to analyze the natural history of classical trigeminal neuralgia in a large cohort of patients, focusing on drug responsiveness, side effects related to CBZ and OXC, and changes in pain characteristics during the course of disease. Findings We selected the last 100 consecutive patients with typical TN who began treatment with CBZ and the last 100 with OXC. All had MRI scans and a complete neurophysiological study of trigeminal reflexes. Among them, 22 were excluded on the basis of neuroradiological or neurophysiological investigations, to avoid the inclusion of patients with possible secondary TN. The initial number of responders was 98% with CBZ with a median dose of 600 mg (range 200–1200), and of 94% with OXC, with a median dose of 1200 mg (range 600–1800). In a mean period of 8.6 months, 27% of responders to CBZ incurred in undesired effects to a level that caused interruption of treatment or a dosage reduction to an unsatisfactory level. In a mean period of 13 months, the same occurred to 18% of responders to OXC. Among patients who had a good initial response, only 3 patients with CBZ and 2 with OXC developed late resistance. During the course of disease, paroxysms worsened in intensity in 3% of patients, and paroxysms duration increased in 2%. We did not observe the onset of a clinically manifest sensory deficit at any time in any patient. Conclusions Unlike common notion, in our large patient sample the worsening of pain with time and the development of late resistance only occurred in a very small minority of patients. CBZ and OXC were confirmed to be efficacious in a large majority of patients, but the side effects caused withdrawal from treatment in an important percentage of patients. These results suggest the opportunity to develop a better tolerated drug. PMID:24912658
Improving condition severity classification with an efficient active learning based framework
Nissim, Nir; Boland, Mary Regina; Tatonetti, Nicholas P.; Elovici, Yuval; Hripcsak, George; Shahar, Yuval; Moskovitch, Robert
2017-01-01
Classification of condition severity can be useful for discriminating among sets of conditions or phenotypes, for example when prioritizing patient care or for other healthcare purposes. Electronic Health Records (EHRs) represent a rich source of labeled information that can be harnessed for severity classification. The labeling of EHRs is expensive and in many cases requires employing professionals with high level of expertise. In this study, we demonstrate the use of Active Learning (AL) techniques to decrease expert labeling efforts. We employ three AL methods and demonstrate their ability to reduce labeling efforts while effectively discriminating condition severity. We incorporate three AL methods into a new framework based on the original CAESAR (Classification Approach for Extracting Severity Automatically from Electronic Health Records) framework to create the Active Learning Enhancement framework (CAESAR-ALE). We applied CAESAR-ALE to a dataset containing 516 conditions of varying severity levels that were manually labeled by seven experts. Our dataset, called the “CAESAR dataset,” was created from the medical records of 1.9 million patients treated at Columbia University Medical Center (CUMC). All three AL methods decreased labelers’ efforts compared to the learning methods applied by the original CAESER framework in which the classifier was trained on the entire set of conditions; depending on the AL strategy used in the current study, the reduction ranged from 48% to 64% that can result in significant savings, both in time and money. As for the PPV (precision) measure, CAESAR-ALE achieved more than 13% absolute improvement in the predictive capabilities of the framework when classifying conditions as severe. These results demonstrate the potential of AL methods to decrease the labeling efforts of medical experts, while increasing accuracy given the same (or even a smaller) number of acquired conditions. We also demonstrated that the methods included in the CAESAR-ALE framework (Exploitation and Combination_XA) are more robust to the use of human labelers with different levels of professional expertise. PMID:27016383