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Sample records for synaptic cleft glutamate

  1. Monte carlo simulation of vesicular release, spatiotemporal distribution of glutamate in synaptic cleft and generation of postsynaptic currents.

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    Glavinovíc, M I

    1999-02-01

    The release of vesicular glutamate, spatiotemporal changes in glutamate concentration in the synaptic cleft and the subsequent generation of fast excitatory postsynaptic currents at a hippocampal synapse were modeled using the Monte Carlo method. It is assumed that glutamate is released from a spherical vesicle through a cylindrical fusion pore into the synaptic cleft and that S-alpha-amino-3-hydroxy -5-methyl-4-isoxazolepropionic acid (AMPA) receptors are uniformly distributed postsynaptically. The time course of change in vesicular concentration can be described by a single exponential, but a slow tail is also observed though only following the release of most of the glutamate. The time constant of decay increases with vesicular size and a lower diffusion constant, and is independent of the initial concentration, becoming markedly shorter for wider fusion pores. The cleft concentration at the fusion pore mouth is not negligible compared to vesicular concentration, especially for wider fusion pores. Lateral equilibration of glutamate is rapid, and within approximately 50 micros all AMPA receptors on average see the same concentration of glutamate. Nevertheless the single-channel current and the number of channels estimated from mean-variance plots are unreliable and different when estimated from rise- and decay-current segments. Greater saturation of AMPA receptor channels provides higher but not more accurate estimates. Two factors contribute to the variability of postsynaptic currents and render the mean-variance nonstationary analysis unreliable, even when all receptors see on average the same glutamate concentration. Firstly, the variability of the instantaneous cleft concentration of glutamate, unlike the mean concentration, first rapidly decreases before slowly increasing; the variability is greater for fewer molecules in the cleft and is spatially nonuniform. Secondly, the efficacy with which glutamate produces a response changes with time. Understanding

  2. A computational study of astrocytic glutamate influence on post-synaptic neuronal excitability.

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    Bronac Flanagan

    2018-04-01

    Full Text Available The ability of astrocytes to rapidly clear synaptic glutamate and purposefully release the excitatory transmitter is critical in the functioning of synapses and neuronal circuits. Dysfunctions of these homeostatic functions have been implicated in the pathology of brain disorders such as mesial temporal lobe epilepsy. However, the reasons for these dysfunctions are not clear from experimental data and computational models have been developed to provide further understanding of the implications of glutamate clearance from the extracellular space, as a result of EAAT2 downregulation: although they only partially account for the glutamate clearance process. In this work, we develop an explicit model of the astrocytic glutamate transporters, providing a more complete description of the glutamate chemical potential across the astrocytic membrane and its contribution to glutamate transporter driving force based on thermodynamic principles and experimental data. Analysis of our model demonstrates that increased astrocytic glutamate content due to glutamine synthetase downregulation also results in increased postsynaptic quantal size due to gliotransmission. Moreover, the proposed model demonstrates that increased astrocytic glutamate could prolong the time course of glutamate in the synaptic cleft and enhances astrocyte-induced slow inward currents, causing a disruption to the clarity of synaptic signalling and the occurrence of intervals of higher frequency postsynaptic firing. Overall, our work distilled the necessity of a low astrocytic glutamate concentration for reliable synaptic transmission of information and the possible implications of enhanced glutamate levels as in epilepsy.

  3. Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

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    Dougherty Patrick M

    2009-07-01

    Full Text Available Abstract Background Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na+ ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents. Results Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd2+. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz repetitive stimulation. Conclusion These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.

  4. Immunocytochemical localization of the glutamate transporter GLT-1 in goldfish (Carassius auratus) retina

    NARCIS (Netherlands)

    Vandenbranden, C. A.; Yazulla, S.; Studholme, K. M.; Kamphuis, W.; Kamermans, M.

    2000-01-01

    Glutamate is the major excitatory neurotransmitter in the retina of vertebrates. Electrophysiological experiments in goldfish and salamander have shown that neuronal glutamate transporters play an important role in the clearance of glutamate from cone synaptic clefts. In this study, the localization

  5. Circadian Regulation of Glutamate Transporters

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    Donají Chi-Castañeda

    2018-06-01

    Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

  6. Bacterial cytolysin during meningitis disrupts the regulation of glutamate in the brain, leading to synaptic damage.

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    Carolin Wippel

    Full Text Available Streptococcus pneumoniae (pneumococcal meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage.

  7. Hydrodynamic flow in a synaptic cleft during exocytosis.

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    Shneider, M N; Gimatdinov, R S; Skorinkin, A I; Kovyazina, I V; Nikolsky, E E

    2012-01-01

    It is shown that exocytosis in a chemical synapse may be accompanied by "microjet" formation due to the overpressure that exists in the vesicles. This mechanism may take place either at complete fusion of a vesicle with the presynaptic membrane or in the so-called kiss-and-run mode of neurotransmitter release. A simple hydrodynamic model of the viscous incompressible flow arising in the synaptic cleft is suggested. The occurrence of hydrodynamic flow (microjet) leads to more efficient transport of neurotransmitter than in the case of classical diffusive transport.

  8. Immune labeling and purification of a 71-kDa glutamate-binding protein from brain synaptic membranes

    International Nuclear Information System (INIS)

    Chen, J.W.; Cunningham, M.D.; Galton, N.; Michaelis, E.K.

    1988-01-01

    Immunoblot studies of synaptic membranes isolated from rat brain using antibodies raised against a previously purified glutamate-binding protein (GBP) indicated labeling of an ∼ 70-kDa protein band. Since the antibodies used were raised against a 14-kDa GBP, the present studies were undertaken to explore the possibility that the 14-kDa protein may have been a proteolytic fragment of a larger M/sub r/ protein in synaptic membranes. The major protein enriched in the most highly purified fractions was a 71-kDa glycoprotein, but a 63-kDa protein was co-purified during most steps of the isolation procedure. The glutamate-binding characteristics of these isolated protein fractions were very similar to those previously described for the 14-kDa GBP, including estimated dissociation constants for L-glutamate binding of 0.25 and 1 + M, inhibition of glutamate binding by azide and cyanide, and a selectivity of the ligand binding site for L-glutamate and L-aspartate. The neuroexcitatory analogs of L-glutamate and L-aspartate, ibotenate, quisqualate, and D-glutamate, inhibited L[ 3 H]glutamate binding to the isolated proteins, as did the antagonist of L-glutamate-induced neuronal excitation, L-glutamate diethylester. On the basis of the lack of any detectable glutamate-related enzyme activity associated with the isolated proteins and the presence of distinguishing sensitivities to analogs that inhibit glutamate transport carriers in synaptic membranes, it is proposed that the 71-kDa protein may be a component of a physiologic glutamate receptor complex in neuronal membranes

  9. Mechanisms of glycine release, which build up synaptic and extrasynaptic glycine levels: the role of synaptic and non-synaptic glycine transporters.

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    Harsing, Laszlo G; Matyus, Peter

    2013-04-01

    Glycine is an amino acid neurotransmitter that is involved in both inhibitory and excitatory neurochemical transmission in the central nervous system. The role of glycine in excitatory neurotransmission is related to its coagonist action at glutamatergic N-methyl-D-aspartate receptors. The glycine levels in the synaptic cleft rise many times higher during synaptic activation assuring that glycine spills over into the extrasynaptic space. Another possible origin of extrasynaptic glycine is the efflux of glycine occurring from astrocytes associated with glutamatergic synapses. The release of glycine from neuronal or glial origins exhibits several differences compared to that of biogenic amines or other amino acid neurotransmitters. These differences appear in an external Ca(2+)- and temperature-dependent manner, conferring unique characteristics on glycine as a neurotransmitter. Glycine transporter type-1 at synapses may exhibit neural and glial forms and plays a role in controlling synaptic glycine levels and the spill over rate of glycine from the synaptic cleft into the extrasynaptic biophase. Non-synaptic glycine transporter type-1 regulates extrasynaptic glycine concentrations, either increasing or decreasing them depending on the reverse or normal mode operation of the carrier molecule. While we can, at best, only estimate synaptic glycine levels at rest and during synaptic activation, glycine concentrations are readily measurable via brain microdialysis technique applied in the extrasynaptic space. The non-synaptic N-methyl-D-aspartate receptor may obtain glycine for activation following its spill over from highly active synapses or from its release mediated by the reverse operation of non-synaptic glycine transporter-1. The sensitivity of non-synaptic N-methyl-D-aspartate receptors to glutamate and glycine is many times higher than that of synaptic N-methyl-D-aspartate receptors making the former type of receptor the primary target for drug action. Synaptic

  10. Valine but not leucine or isoleucine supports neurotransmitter glutamate synthesis during synaptic activity in cultured cerebellar neurons

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    Bak, Lasse Kristoffer; Johansen, Maja L.; Schousboe, Arne

    2012-01-01

    Synthesis of neuronal glutamate from a-ketoglutarate for neurotransmission necessitates an amino group nitrogen donor; however, it is not clear which amino acid(s) serves this role. Thus, the ability of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, to act as amino...... group nitrogen donors for synthesis of vesicular neurotransmitter glutamate was investigated in cultured mouse cerebellar (primarily glutamatergic) neurons. The cultures were superfused in the presence of (15) N-labeled BCAAs, and synaptic activity was induced by pulses of N-methyl-D-aspartate (300 µ......]valine was able to maintain the amount of vesicular glutamate during synaptic activity. This indicates that, among the BCAAs, only valine supports the increased need for synthesis of vesicular glutamate. © 2012 Wiley Periodicals, Inc....

  11. A Computational Model to Investigate Astrocytic Glutamate Uptake Influence on Synaptic Transmission and Neuronal Spiking

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    Sushmita Lakshmi Allam

    2012-10-01

    Full Text Available Over the past decades, our view of astrocytes has switched from passive support cells to active processing elements in the brain. The current view is that astrocytes shape neuronal communication and also play an important role in many neurodegenerative diseases. Despite the growing awareness of the importance of astrocytes, the exact mechanisms underlying neuron-astrocyte communication and the physiological consequences of astrocytic-neuronal interactions remain largely unclear. In this work, we define a modeling framework that will permit to address unanswered questions regarding the role of astrocytes. Our computational model of a detailed glutamatergic synapse facilitates the analysis of neural system responses to various stimuli and conditions that are otherwise difficult to obtain experimentally, in particular the readouts at the sub-cellular level. In this paper, we extend a detailed glutamatergic synaptic model, to include astrocytic glutamate transporters. We demonstrate how these glial transporters, responsible for the majority of glutamate uptake, modulate synaptic transmission mediated by ionotropic AMPA and NMDA receptors at glutamatergic synapses. Furthermore, we investigate how these local signaling effects at the synaptic level are translated into varying spatio-temporal patterns of neuron firing. Paired pulse stimulation results reveal that the effect of astrocytic glutamate uptake is more apparent when the input inter-spike interval is sufficiently long to allow the receptors to recover from desensitization. These results suggest an important functional role of astrocytes in spike timing dependent processes and demand further investigation of the molecular basis of certain neurological diseases specifically related to alterations in astrocytic glutamate uptake, such as epilepsy.

  12. Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc.

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    Anderson, Charles T; Radford, Robert J; Zastrow, Melissa L; Zhang, Daniel Y; Apfel, Ulf-Peter; Lippard, Stephen J; Tzounopoulos, Thanos

    2015-05-19

    Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling.

  13. Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc

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    Anderson, Charles T.; Radford, Robert J.; Zastrow, Melissa L.; Zhang, Daniel Y.; Apfel, Ulf-Peter; Lippard, Stephen J.; Tzounopoulos, Thanos

    2015-01-01

    Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling. PMID:25947151

  14. pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

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    McCrimmon, Donald R.; Martina, Marco

    2013-01-01

    The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with dl-threo-β-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter d-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. PMID:23615553

  15. Synaptic Cell Adhesion

    OpenAIRE

    Missler, Markus; Südhof, Thomas C.; Biederer, Thomas

    2012-01-01

    Chemical synapses are asymmetric intercellular junctions that mediate synaptic transmission. Synaptic junctions are organized by trans-synaptic cell adhesion molecules bridging the synaptic cleft. Synaptic cell adhesion molecules not only connect pre- and postsynaptic compartments, but also mediate trans-synaptic recognition and signaling processes that are essential for the establishment, specification, and plasticity of synapses. A growing number of synaptic cell adhesion molecules that inc...

  16. Raindrops of synaptic noise on dual excitability landscape: an approach to astrocyte network modelling

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    Verisokin, Andrey Yu.; Postnov, Dmitry E.; Verveyko, Darya V.; Brazhe, Alexey R.

    2018-04-01

    The most abundant non-neuronal cells in the brain, astrocytes, populate all parts of the central nervous system (CNS). Astrocytic calcium activity ranging from subcellular sparkles to intercellular waves is believed to be the key to a plethora of regulatory pathways in the central nervous system from synaptic plasticity to blood flow regulation. Modeling of the calcium wave initiation and transmission and their spatiotemporal dynamics is therefore an important step stone in understanding the crucial cogs of cognition. Astrocytes are active sensors of ongoing neuronal and synaptic activity, and neurotransmitters diffusing from the synaptic cleft make a strong impact on the astrocytic activity. Here we propose a model describing the patterns of calcium wave formation at a single cell level and discuss the interplay between astrocyte shape the calcium waves dynamics driven by local stochastic surges of glutamate simulating synaptic activity.

  17. Effects of 17beta-estradiol on glutamate synaptic transmission and neuronal excitability in the rat medial vestibular nuclei.

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    Grassi, S; Frondaroli, A; Scarduzio, M; Dutia, M B; Dieni, C; Pettorossi, V E

    2010-02-17

    We investigated the effects of the neurosteroid 17beta-estradiol (E(2)) on the evoked and spontaneous activity of rat medial vestibular nucleus (MVN) neurons in brainstem slices. E(2) enhances the synaptic response to vestibular nerve stimulation in type B neurons and depresses the spontaneous discharge in both type A and B neurons. The amplitude of the field potential, as well as the excitatory post-synaptic potential (EPSP) and current (EPSC), in type B neurons, are enhanced by E(2). Both effects are long-term phenomena since they outlast the drug washout. The enhancement of synaptic response is mainly due to facilitation of glutamate release mediated by pre-synaptic N-methyl-D-aspartate receptors (NMDARs), since the reduction of paired pulse ratio (PPR) and the increase of miniature EPSC frequency after E(2) are abolished under D-(-)-2-amino-5-phosphonopentanoic acid (AP-5). E(2) also facilitates post-synaptic NMDARs, but it does not affect directly alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and group I-metabotropic glutamate receptors (mGluRs-I). In contrast, the depression of the spontaneous discharge of type A and type B neurons appears to depend on E(2) modulation of intrinsic ion conductances, as the effect remains after blockade of glutamate, GABA and glycine receptors (GlyRs). The net effect of E(2) is to enhance the signal-to-noise ratio of the synaptic response in type B neurons, relative to resting activity of all MVN neurons. These findings provide evidence for a novel potential mechanism to modulate the responsiveness of vestibular neurons to afferent inputs, and so regulate vestibular function in vivo.

  18. Glutamate transporter activity promotes enhanced Na+/K+-ATPase -mediated extracellular K+ management during neuronal activity

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    Larsen, Brian R; Holm, Rikke; Vilsen, Bente

    2016-01-01

    , in addition, Na+ /K+ -ATPase-mediated K+ clearance could be governed by astrocytic [Na+ ]i . During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+ -coupled glutamate transporters, thereby elevating [Na+ ]i . It thus remains unresolved whether...... the different Na+ /K+ -ATPase isoforms are controlled by [K+ ]o or [Na+ ]i during neuronal activity. Hippocampal slice recordings of stimulus-induced [K+ ]o transients with ion-sensitive microelectrodes revealed reduced Na+ /K+ -ATPase-mediated K+ management upon parallel inhibition of the glutamate transporter......+ affinity to the α1 and α2 isoforms than the β2 isoform. In summary, enhanced astrocytic Na+ /K+ -ATPase-dependent K+ clearance was obtained with parallel glutamate transport activity. The astrocytic Na+ /K+ -ATPase isoform constellation α2β1 appeared to be specifically geared to respond to the [Na+ ]i...

  19. Effects of dopamine and glutamate on synaptic plasticity: a computational modeling approach for drug abuse as comorbidity in mood disorders.

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    Qi, Z; Kikuchi, S; Tretter, F; Voit, E O

    2011-05-01

    Major depressive disorder (MDD) affects about 16% of the general population and is a leading cause of death in the United States and around the world. Aggravating the situation is the fact that "drug use disorders" are highly comorbid in MDD patients, and VICE VERSA. Drug use and MDD share a common component, the dopamine system, which is critical in many motivation and reward processes, as well as in the regulation of stress responses in MDD. A potentiating mechanism in drug use disorders appears to be synaptic plasticity, which is regulated by dopamine transmission. In this article, we describe a computational model of the synaptic plasticity of GABAergic medium spiny neurons in the nucleus accumbens, which is critical in the reward system. The model accounts for effects of both dopamine and glutamate transmission. Model simulations show that GABAergic medium spiny neurons tend to respond to dopamine stimuli with synaptic potentiation and to glutamate signals with synaptic depression. Concurrent dopamine and glutamate signals cause various types of synaptic plasticity, depending on input scenarios. Interestingly, the model shows that a single 0.5 mg/kg dose of amphetamine can cause synaptic potentiation for over 2 h, a phenomenon that makes synaptic plasticity of medium spiny neurons behave quasi as a bistable system. The model also identifies mechanisms that could potentially be critical to correcting modifications of synaptic plasticity caused by drugs in MDD patients. An example is the feedback loop between protein kinase A, phosphodiesterase, and the second messenger cAMP in the postsynapse. Since reward mechanisms activated by psychostimulants could be crucial in establishing addiction comorbidity in patients with MDD, this model might become an aid for identifying and targeting specific modules within the reward system and lead to a better understanding and potential treatment of comorbid drug use disorders in MDD. © Georg Thieme Verlag KG Stuttgart · New

  20. Direct visualization of glutamate transporter elevator mechanism by high-speed AFM.

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    Ruan, Yi; Miyagi, Atsushi; Wang, Xiaoyu; Chami, Mohamed; Boudker, Olga; Scheuring, Simon

    2017-02-14

    Glutamate transporters are essential for recovery of the neurotransmitter glutamate from the synaptic cleft. Crystal structures in the outward- and inward-facing conformations of a glutamate transporter homolog from archaebacterium Pyrococcus horikoshii , sodium/aspartate symporter Glt Ph , suggested the molecular basis of the transporter cycle. However, dynamic studies of the transport mechanism have been sparse and indirect. Here we present high-speed atomic force microscopy (HS-AFM) observations of membrane-reconstituted Glt Ph at work. HS-AFM movies provide unprecedented real-space and real-time visualization of the transport dynamics. Our results show transport mediated by large amplitude 1.85-nm "elevator" movements of the transport domains consistent with previous crystallographic and spectroscopic studies. Elevator dynamics occur in the absence and presence of sodium ions and aspartate, but stall in sodium alone, providing a direct visualization of the ion and substrate symport mechanism. We show unambiguously that individual protomers within the trimeric transporter function fully independently.

  1. Activity of the lactate-alanine shuttle is independent of glutamate-glutamine cycle activity in cerebellar neuronal-astrocytic cultures

    DEFF Research Database (Denmark)

    Bak, Lasse K; Sickmann, Helle M; Schousboe, Arne

    2004-01-01

    The glutamate-glutamine cycle describes the neuronal release of glutamate into the synaptic cleft, astrocytic uptake, and conversion into glutamine, followed by release for use as a neuronal glutamate precursor. This only explains the fate of the carbon atoms, however, and not that of the ammonia....... Recently, a role for alanine has been proposed in transfer of ammonia between glutamatergic neurons and astrocytes, denoted the lactate-alanine shuttle (Waagepetersen et al. [ 2000] J. Neurochem. 75:471-479). The role of alanine in this context has been studied further using cerebellar neuronal cultures...... and corresponding neuronal-astrocytic cocultures. A superfusion paradigm was used to induce repetitively vesicular glutamate release by N-methyl-D-aspartate (NMDA) in the neurons, allowing the relative activity dependency of the lactate-alanine shuttle to be assessed. [(15)N]Alanine (0.2 mM), [2-(15)N]/[5-(15)N...

  2. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions.

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    Melanie A Samuel

    Full Text Available As synapses form and mature the synaptic partners produce organizing molecules that regulate each other's differentiation and ensure precise apposition of pre- and post-synaptic specializations. At the skeletal neuromuscular junction (NMJ, these molecules include agrin, a nerve-derived organizer of postsynaptic differentiation, and synaptic laminins, muscle-derived organizers of presynaptic differentiation. Both become concentrated in the synaptic cleft as the NMJ develops and are retained in adulthood. Here, we used mutant mice to ask whether these organizers are also required for synaptic maintenance. Deletion of agrin from a subset of adult motor neurons resulted in the loss of acetylcholine receptors and other components of the postsynaptic apparatus and synaptic cleft. Nerve terminals also atrophied and eventually withdrew from muscle fibers. On the other hand, mice lacking the presynaptic organizer laminin-α4 retained most of the synaptic cleft components but exhibited synaptic alterations reminiscent of those observed in aged animals. Although we detected no marked decrease in laminin or agrin levels at aged NMJs, we observed alterations in the distribution and organization of these synaptic cleft components suggesting that such changes could contribute to age-related synaptic disassembly. Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs.

  3. Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

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    Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

    2015-05-01

    Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. The 'glial' glutamate transporter, EAAT2 (Glt-1) accounts for high affinity glutamate uptake into adult rodent nerve endings.

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    Suchak, Sachin K; Baloyianni, Nicoletta V; Perkinton, Michael S; Williams, Robert J; Meldrum, Brian S; Rattray, Marcus

    2003-02-01

    The excitatory amino acid transporters (EAAT) removes neurotransmitters glutamate and aspartate from the synaptic cleft. Most CNS glutamate uptake is mediated by EAAT2 into glia, though nerve terminals show evidence for uptake, through an unknown transporter. Reverse-transcriptase PCR identified the expression of EAAT1, EAAT2, EAAT3 and EAAT4 mRNAs in primary cultures of mouse cortical or striatal neurones. We have used synaptosomes and glial plasmalemmal vesicles (GPV) from adult mouse and rat CNS to identify the nerve terminal transporter. Western blotting showed detectable levels of the transporters EAAT1 (GLAST) and EAAT2 (Glt-1) in both synaptosomes and GPVs. Uptake of [3H]D-aspartate or [3H]L-glutamate into these preparations revealed sodium-dependent uptake in GPV and synaptosomes which was inhibited by a range of EAAT blockers: dihydrokainate, serine-o-sulfate, l-trans-2,4-pyrrolidine dicarboxylate (PDC) (+/-)-threo-3-methylglutamate and (2S,4R )-4-methylglutamate. The IC50 values found for these compounds suggested functional expression of the 'glial, transporter, EAAT2 in nerve terminals. Additionally blockade of the majority EAAT2 uptake sites with 100 micro m dihydrokainate, failed to unmask any functional non-EAAT2 uptake sites. The data presented in this study indicate that EAAT2 is the predominant nerve terminal glutamate transporter in the adult rodent CNS.

  5. Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

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    Dickenson Anthony H

    2009-02-01

    Full Text Available Abstract Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1 has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal

  6. Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

    Science.gov (United States)

    Nguyen, David; Deng, Ping; Matthews, Elizabeth A; Kim, Doo-Sik; Feng, Guoping; Dickenson, Anthony H; Xu, Zao C; Luo, Z David

    2009-01-01

    Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous

  7. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons.

    Science.gov (United States)

    Eastwood, S L; Harrison, P J

    2005-03-01

    Synaptic protein gene expression is altered in schizophrenia. In the hippocampal formation there may be particular involvement of glutamatergic neurons and their synapses, but overall the profile remains unclear. In this in situ hybridization histochemistry (ISHH) study, we examined four informative synaptic protein transcripts: vesicular glutamate transporter (VGLUT) 1, VGLUT2, complexin I, and complexin II, in dorsolateral prefrontal cortex (DPFC), superior temporal cortex (STC), and hippocampal formation, in 13 subjects with schizophrenia and 18 controls. In these areas, VGLUT1 and complexin II are expressed primarily by excitatory neurons, whereas complexin I is mainly expressed by inhibitory neurons. In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC. Hippocampal VGLUT1 mRNA declined with age selectively in the schizophrenia group. VGLUT2 mRNA was not quantifiable due to its low level. The data provide additional evidence for a synaptic pathology in schizophrenia, in terms of a reduced expression of three synaptic protein genes. In the hippocampus, the loss of VGLUT1 mRNA supports data indicating that glutamatergic presynaptic deficits are prominent, whereas the pattern of results in temporal and frontal cortex suggests broadly similar changes may affect inhibitory and excitatory neurons. The impairment of synaptic transmission implied by the synaptic protein reductions may contribute to the dysfunction of cortical neural circuits that characterises the disorder.

  8. Solubilization, partial purification, and reconstitution of glutamate- and N-methyl-D-aspartate-activated cation channels from brain synaptic membranes

    International Nuclear Information System (INIS)

    Ly, A.M.; Michaelis, E.K.

    1991-01-01

    L-Glutamate-activated cation channel proteins from rat brain synaptic membranes were solubilized, partially purified, and reconstituted into liposomes. Optimal conditions for solubilization and reconstitution included treatment of the membranes with nonionic detergents in the presence of neutral phospholipids plus glycerol. Quench-flow procedures were developed to characterize the rapid kinetics of ion flux induced by receptor agonists. [ 14 C]Methylamine, a cation that permeates through the open channel of both vertebrate and invertebrate glutamate receptors, was used to measure the activity of glutamate receptor-ion channel complexes in reconstituted liposomes. L-Glutamate caused an increase in the rate of [ 14 C]methylamine influx into liposomes reconstituted with either solubilized membrane proteins or partially purified glutamate-binding proteins. Of the major glutamate receptor agonists, only N-methyl-D-aspartate activated cation fluxes in liposomes reconstituted with glutamate-binding proteins. In liposomes reconstituted with glutamate-binding proteins, N-methyl-D-aspartate- or glutamate-induced influx of NA + led to a transient increase in the influx of the lipid-permeable anion probe S 14 CN - . These results indicate the functional reconstitution of N-methyl-D-aspartate-sensitive glutamate receptors and the role of the ∼69-kDa protein in the function of these ion channels

  9. Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2001-08-01

    The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular

  10. Effects of metabotropic glutamate receptor block on the synaptic transmission and plasticity in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Malfagia, C; Pettorossi, V E

    1998-11-01

    In rat brainstem slices, we investigated the possible role of metabotropic glutamate receptors in modulating the synaptic transmission within the medial vestibular nuclei, under basal and plasticity inducing conditions. We analysed the effect of the metabotropic glutamate receptor antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine on the amplitude of the field potentials and latency of unitary potentials evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation, and on the induction and maintenance of long-term potentiation, after high-frequency stimulation. Two effects were observed, consisting of a slight increase of the field potentials and reduction of unit latency during the drug infusion, and a further long-lasting development of these modifications after the drug wash-out. The long-term effect depended on N-methyl-D-aspartate receptor activation, as D,L-2-amino-5-phosphonopentanoic acid prevented its development. We suggest that (R,S)-alpha-methyl-4carboxyphenylglycine enhances the vestibular responses and induces N-methyl-D-aspartate-dependent long-term potentiation by increasing glutamate release, through the block of presynaptic metabotropic glutamate receptors which actively inhibit it. The block of these receptors was indirectly supported by the fact that the agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid reduced the vestibular responses and blocked the induction of long-term potentiation by high-frequency stimulation. The simultaneous block of metabotropic glutamate receptors facilitating synaptic plasticity, impedes the full expression of the long-term effect throughout the (R,S)-alpha-methyl-4-carboxyphenylglycine infusion. The involvement of such a facilitatory mechanism in the potentiation is supported by its reversible reduction following a second (R,S)-alpha-methyl-4-carboxyphenylglycine infusion. The drug also reduced the expression of potentiation induced by high-frequency stimulation

  11. Can a Selective Serotonin Reuptake Inhibitor Act as a Glutamatergic Modulator?

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    Marcos Emilio Frizzo, PhD

    2017-01-01

    Full Text Available Sertraline (Zoloft and fluoxetine (Prozac are selective serotonin reuptake inhibitors whose antidepressant mechanism of action is classically attributed to an elevation of the extracellular levels of serotonin in the synaptic cleft. However, the biological effects of these drugs seem to be more complex than their traditionally described mechanism of action. Among their actions is the inhibition of different types of Na+ and K+ channels, as well as of glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system within physiological conditions, and this excitatory neurotransmitter is removed from the synaptic cleft by astrocyte transporters. This transport depends upon a hyperpolarized membrane potential in astrocytes that is mainly maintained by Kir4.1 K+ channels. The impairment of the Kir4.1 channel activity reduces driving force for the glutamate transporter, resulting in an accumulation of extracellular glutamate. It has been shown that sertraline and fluoxetine inhibit Kir4.1 K+ channels. Recently, we demonstrated that sertraline reduces glutamate uptake in human platelets, which contain a high-affinity Na+-dependent glutamate uptake system, with kinetic and pharmacological properties similar to astrocytes in the central nervous system. Considering these similarities between human platelets and astrocytes, one might ask if sertraline could potentially reduce glutamate clearance in the synaptic cleft and consequently modulate glutamatergic transmission. This possibility merits investigation, since it may provide additional information regarding the mechanism of action and perhaps the side effects of these antidepressants.

  12. Posttranslational Modification Biology of Glutamate Receptors and Drug Addiction

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    Li-Min eMao

    2011-03-01

    Full Text Available Posttranslational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues on their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling and protein-protein interactions, subcellular redistribution (trafficking, endocytosis, synaptic delivery and clustering, and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamines. Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.

  13. Two Classes of Secreted Synaptic Organizers in the Central Nervous System.

    Science.gov (United States)

    Yuzaki, Michisuke

    2018-02-10

    Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of pre- and/or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft. These include Lgi1, Cbln1, neuronal pentraxins, Hevin, thrombospondins, and glypicans. Diffusible secreted factors, such as Wnts, fibroblast growth factors, and semaphorins, tend to act from a distance. In contrast, ESPs remain at the synaptic cleft and often help synaptic adhesion and/or accumulation of postsynaptic receptors. Many fundamental questions remain about when, how, and why various synaptic organizers establish and modify the vast numbers of connections during development and throughout life.

  14. Dbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response.

    Science.gov (United States)

    Wang, Manyu; Chen, Pei-Yi; Wang, Chien-Hsiang; Lai, Tzu-Ting; Tsai, Pei-I; Cheng, Ying-Ju; Kao, Hsiu-Hua; Chien, Cheng-Ting

    2016-10-01

    In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK.

  15. Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors

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    Yu-Wei Wu

    2012-05-01

    Full Text Available Synaptic NMDA receptors (NMDARs are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.

  16. Dbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response.

    Directory of Open Access Journals (Sweden)

    Manyu Wang

    2016-10-01

    Full Text Available In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ. In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK.

  17. Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors

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    Yao, Yongneng; Harrison, Chris B.; Freddolino, Peter L.; Schulten, Klaus; Mayer, Mark L. (UIUC); (NIH)

    2008-10-27

    NR3 subtype glutamate receptors have a unique developmental expression profile, but are the least well-characterized members of the NMDA receptor gene family, which have key roles in synaptic plasticity and brain development. Using ligand binding assays, crystallographic analysis, and all atom MD simulations, we investigate mechanisms underlying the binding by NR3A and NR3B of glycine and D-serine, which are candidate neurotransmitters for NMDA receptors containing NR3 subunits. The ligand binding domains of both NR3 subunits adopt a similar extent of domain closure as found in the corresponding NR1 complexes, but have a unique loop 1 structure distinct from that in all other glutamate receptor ion channels. Within their ligand binding pockets, NR3A and NR3B have strikingly different hydrogen bonding networks and solvent structures from those found in NR1, and fail to undergo a conformational rearrangement observed in NR1 upon binding the partial agonist ACPC. MD simulations revealed numerous interdomain contacts, which stabilize the agonist-bound closed-cleft conformation, and a novel twisting motion for the loop 1 helix that is unique in NR3 subunits.

  18. Factors Influencing Short-term Synaptic Plasticity in the Avian Cochlear Nucleus Magnocellularis

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    Jason Tait Sanchez Quinones

    2015-01-01

    Full Text Available Defined as reduced neural responses during high rates of activity, synaptic depression is a form of short-term plasticity important for the temporal filtering of sound. In the avian cochlear nucleus magnocellularis (NM, an auditory brainstem structure, mechanisms regulating short-term synaptic depression include pre-, post-, and extrasynaptic factors. Using varied paired-pulse stimulus intervals, we found that the time course of synaptic depression lasts up to four seconds at late-developing NM synapses. Synaptic depression was largely reliant on exogenous Ca 2+ -dependent probability of presynaptic neurotransmitter release, and to a lesser extent, on the desensitization of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPA-R. Interestingly, although extrasynaptic glutamate clearance did not play a significant role in regulating synaptic depression, blocking glutamate clearance at early-developing synapses altered synaptic dynamics, changing responses from depression to facilitation. These results suggest a developmental shift in the relative reliance on pre-, post-, and extrasynaptic factors in regulating short-term synaptic plasticity in NM.

  19. A Glutamate Homeostat Controls the Presynaptic Inhibition of Neurotransmitter Release

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    Xiling Li

    2018-05-01

    Full Text Available Summary: We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ. We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes. Furthermore, homeostatic depression is only induced through excess presynaptic glutamate release and operates with disregard to the postsynaptic response. We propose that two independent homeostats modulate presynaptic efficacy at the Drosophila NMJ: one is an intercellular signaling system that potentiates synaptic strength following diminished postsynaptic excitability, while the other adaptively modulates presynaptic glutamate release through an autocrine mechanism without feedback from the postsynaptic compartment. : Homeostatic mechanisms stabilize synaptic strength, but the signaling systems remain enigmatic. Li et al. suggest the existence of a homeostat operating at the Drosophila neuromuscular junction that responds to excess glutamate through an autocrine mechanism to adaptively inhibit presynaptic neurotransmitter release. This system parallels forms of plasticity at central synapses. Keywords: homeostatic synaptic plasticity, glutamate homeostasis, synaptic depression, Drosophila neuromuscular junction

  20. Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds.

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    Yijen A Huang

    Full Text Available Recent studies suggest that l-glutamate may be an efferent transmitter released from axons innervating taste buds. In this report, we determined the types of ionotropic synaptic glutamate receptors present on taste cells and that underlie this postulated efferent transmission. We also studied what effect glutamate exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura 2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings show that a large fraction of Presynaptic (Type III taste bud cells (∼50% respond to 100 µM glutamate, NMDA, or kainic acid (KA with an increase in intracellular Ca(2+. In contrast, Receptor (Type II taste cells rarely (4% responded to 100 µM glutamate. At this concentration and with these compounds, these agonists activate glutamatergic synaptic receptors, not glutamate taste (umami receptors. Moreover, applying glutamate, NMDA, or KA caused taste buds to secrete 5-HT, a Presynaptic taste cell transmitter, but not ATP, a Receptor cell transmitter. Indeed, glutamate-evoked 5-HT release inhibited taste-evoked ATP secretion. The findings are consistent with a role for glutamate in taste buds as an inhibitory efferent transmitter that acts via ionotropic synaptic glutamate receptors.

  1. Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds.

    Science.gov (United States)

    Huang, Yijen A; Grant, Jeff; Roper, Stephen

    2012-01-01

    Recent studies suggest that l-glutamate may be an efferent transmitter released from axons innervating taste buds. In this report, we determined the types of ionotropic synaptic glutamate receptors present on taste cells and that underlie this postulated efferent transmission. We also studied what effect glutamate exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura 2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings show that a large fraction of Presynaptic (Type III) taste bud cells (∼50%) respond to 100 µM glutamate, NMDA, or kainic acid (KA) with an increase in intracellular Ca(2+). In contrast, Receptor (Type II) taste cells rarely (4%) responded to 100 µM glutamate. At this concentration and with these compounds, these agonists activate glutamatergic synaptic receptors, not glutamate taste (umami) receptors. Moreover, applying glutamate, NMDA, or KA caused taste buds to secrete 5-HT, a Presynaptic taste cell transmitter, but not ATP, a Receptor cell transmitter. Indeed, glutamate-evoked 5-HT release inhibited taste-evoked ATP secretion. The findings are consistent with a role for glutamate in taste buds as an inhibitory efferent transmitter that acts via ionotropic synaptic glutamate receptors.

  2. Immunochemical characterization of the brain glutamate binding protein

    International Nuclear Information System (INIS)

    Roy, S.

    1986-01-01

    A glutamate binding protein (GBP) was purified from bovine and rat brain to near homogeneity. Polyclonal antibodies were raised against this protein. An enzyme-linked-immunosorbent-assay was used to quantify and determine the specificity of the antibody response. The antibodies were shown to strongly react with bovine brain GBP and the analogous protein from rat brain. The antibodies did not show any crossreactivity with the glutamate metabolizing enzymes, glutamate dehydrogenase, glutamine synthetase and glutamyl transpeptidase, however it crossreacted moderately with glutamate decarboxylase. The antibodies were also used to define the possible physiologic activity of GBP in synaptic membranes. The antibodies were shown: (i) to inhibit the excitatory amino-acid stimulation of thiocyanate (SCN)flux, (ii) had no effect on transport of L-Glutamic acid across the synaptic membrane, and (iii) had no effect on the depolarization-induced release of L-glutamate. When the anti-GBP antibodies were used to localize and quantify the GBP distribution in various subcellular fractions and in brain tissue samples, it was found that the hippocampus had the highest immunoreactivity followed by the cerebral cortex, cerebellar cortex and caudate-putamen. The distribution of immunoreactivity in the subcellular fraction were as follows: synaptic membranes > crude mitochondrial fraction > homogenate > myelin. In conclusion these studies suggest that: (a) the rat brain GBP and the bovine brain GBP are immunologically homologous protein, (b) there are no structural similarities between the GBP and the glutamate metabolizing enzymes with the exception of glutamate decarboxylase and (c) the subcellular and regional distribution of the GBP immunoreactivity followed a similar pattern as observed for L-[ 3 H]-binding

  3. Novel Functional Properties of Drosophila CNS Glutamate Receptors

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    Li, Yan; Dharkar, Poorva; Han, Tae-Hee; Serpe, Mihaela; Lee, Chi-Hon; Mayer, Mark L.

    2016-12-01

    Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation by its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation.

  4. Dual Effects of TARP γ-2 on Glutamate Efficacy Can Account for AMPA Receptor Autoinactivation

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    Ian D. Coombs

    2017-08-01

    Full Text Available Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs associated with transmembrane AMPAR regulatory proteins (TARPs. At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy. Simulations show that, by shifting the balance between AMPAR activation and desensitization, TARPs can markedly facilitate the transduction of spillover-mediated synaptic signaling. Furthermore, the dual effects of TARPs can account for biphasic steady-state glutamate concentration-response curves—a phenomenon termed “autoinactivation,” previously thought to reflect desensitization-mediated AMPAR/TARP dissociation.

  5. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

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    Rudenko, Gabby (Texas-MED)

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

  6. Modulation of synaptic plasticity by stress hormone associates with plastic alteration of synaptic NMDA receptor in the adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Yiu Chung Tse

    Full Text Available Stress exerts a profound impact on learning and memory, in part, through the actions of adrenal corticosterone (CORT on synaptic plasticity, a cellular model of learning and memory. Increasing findings suggest that CORT exerts its impact on synaptic plasticity by altering the functional properties of glutamate receptors, which include changes in the motility and function of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of glutamate receptor (AMPAR that are responsible for the expression of synaptic plasticity. Here we provide evidence that CORT could also regulate synaptic plasticity by modulating the function of synaptic N-methyl-D-aspartate receptors (NMDARs, which mediate the induction of synaptic plasticity. We found that stress level CORT applied to adult rat hippocampal slices potentiated evoked NMDAR-mediated synaptic responses within 30 min. Surprisingly, following this fast-onset change, we observed a slow-onset (>1 hour after termination of CORT exposure increase in synaptic expression of GluN2A-containing NMDARs. To investigate the consequences of the distinct fast- and slow-onset modulation of NMDARs for synaptic plasticity, we examined the formation of long-term potentiation (LTP and long-term depression (LTD within relevant time windows. Paralleling the increased NMDAR function, both LTP and LTD were facilitated during CORT treatment. However, 1-2 hours after CORT treatment when synaptic expression of GluN2A-containing NMDARs is increased, bidirectional plasticity was no longer facilitated. Our findings reveal the remarkable plasticity of NMDARs in the adult hippocampus in response to CORT. CORT-mediated slow-onset increase in GluN2A in hippocampal synapses could be a homeostatic mechanism to normalize synaptic plasticity following fast-onset stress-induced facilitation.

  7. Glutamate metabolism in the brain focusing on astrocytes

    DEFF Research Database (Denmark)

    Schousboe, Arne; Scafidi, Susanna; Bak, Lasse Kristoffer

    2014-01-01

    , as well as in nitrogen trafficking and ammonia homeostasis in brain. The anatomical specialization of astrocytic endfeet enables these cells to rapidly and efficiently remove neurotransmitters from the synaptic cleft to maintain homeostasis, and to provide glutamine to replenish neurotransmitter pools...

  8. Electric Dipole Theory of Chemical Synaptic Transmission

    Science.gov (United States)

    Wei, Ling Y.

    1968-01-01

    In this paper we propose that chemicals such as acetylcholine are electric dipoles which when oriented and arranged in a large array could produce an electric field strong enough to drive positive ions over the junction barrier of the post-synaptic membrane and thus initiate excitation or produce depolarization. This theory is able to explain a great number of facts such as cleft size, synaptic delay, nonregeneration, subthreshold integration, facilitation with repetition, and the calcium and magnesium effects. It also shows why and how acetylcholine could act as excitatory or inhibitory transmitters under different circumstances. Our conclusion is that the nature of synaptic transmission is essentially electrical, be it mediated by electrical or chemical transmitters. PMID:4296121

  9. VGLUTs and Glutamate Synthesis—Focus on DRG Neurons and Pain

    Directory of Open Access Journals (Sweden)

    Mariana Malet

    2015-12-01

    Full Text Available The amino acid glutamate is the principal excitatory transmitter in the nervous system, including in sensory neurons that convey pain sensation from the periphery to the brain. It is now well established that a family of membrane proteins, termed vesicular glutamate transporters (VGLUTs, serve a critical function in these neurons: they incorporate glutamate into synaptic vesicles. VGLUTs have a central role both under normal neurotransmission and pathological conditions, such as neuropathic or inflammatory pain. In the present short review, we will address VGLUTs in the context of primary afferent neurons. We will focus on the role of VGLUTs in pain triggered by noxious stimuli, peripheral nerve injury, and tissue inflammation, as mostly explored in transgenic mice. The possible interplay between glutamate biosynthesis and VGLUT-dependent packaging in synaptic vesicles, and its potential impact in various pain states will be presented.

  10. Excitatory amino acid transporters as potential drug targets

    DEFF Research Database (Denmark)

    Bunch, Lennart; Erichsen, Mette Navy; Jensen, Anders Asbjørn

    2009-01-01

    BACKGROUND: Excitatory amino acid transporters (EAATs) are transmembrane proteins responsible for the uptake of (S)-glutamate (Glu) from the synaptic cleft, thereby terminating the glutamatergic neurotransmitter signal. Today five subtypes have been identified. Except for EAAT2, their individual...

  11. High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus.

    Science.gov (United States)

    Baude, A; Nusser, Z; Molnár, E; McIlhinney, R A; Somogyi, P

    1995-12-01

    particles for the GluRA, GluRB/C and GluRD subunits were present at type 1 synaptic membrane specializations on dendritic spines of pyramidal cells throughout all layers of the CA1 and CA3 areas. The most densely labelled synapses tended to be on the largest spines and many smaller spines remained unlabelled. Immunoparticle density at type 1 synapses on dendritic shafts of some non-principal cells was consistently higher than at labelled synapses of dendritic spines of pyramidal cells. Synapses established between dendritic spines and mossy fibre terminals, were immunoreactive for all studied subunits in stratum lucidum of the CA3 area. The postembedding immunogold method revealed that the AMPA type receptors are concentrated within the main body of the anatomically defined type 1 (asymmetrical) synaptic junction. Often only a part of the membrane specialization showed clustered immunoparticles. There was a sharp decrease in immunoreactive receptor density at the edge of the synaptic specialization. Immunolabelling was consistently demonstrated at extrasynaptic sites on dendrites, dendritic spines and somata. The results demonstrate that the GluRA, B/C and D subunits of the AMPA type glutamate receptor are present in many of the glutamatergic synapses formed by the entorhinal, CA3 pyramidal and mossy fibre terminals. Some interneurons have a higher density of AMPA type receptors in their asymmetrical afferent synapses than pyramidal cells. This may contribute to a lower activation threshold of interneurons as compared to principal cells by the same afferents in the hippocampal formation.

  12. The Predominance of Electric Transport in Synaptic Transmission

    OpenAIRE

    Hamid Reza Noori

    2008-01-01

    The quantitative description of the motion of neurotransmitters in the synaptic cleft appears to be one of the most difficult problems in the modeling of synapses. Here we show in contradiction to the common view, that this process is merely governed by electric transport than diffusion forces.

  13. Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid

    DEFF Research Database (Denmark)

    Sagot, Emanuelle; Jensen, Anders A.; Pickering, Darryl S

    2008-01-01

    In the mammalian central nervous system (CNS), the action of sodium dependent excitatory amino acid transporters (EAATs) is responsible for termination of glutamatergic neurotransmission by reuptake of ( S) -glutamate (Glu) from the synaptic cleft. Five EAAT subtypes have been identified, of which...

  14. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

    Directory of Open Access Journals (Sweden)

    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  15. Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission

    DEFF Research Database (Denmark)

    Frigerio, Francesca; Karaca, Melis; De Roo, Mathias

    2012-01-01

    Glutamate dehydrogenase (GDH), encoded by GLUD1, participates in the breakdown and synthesis of glutamate, the main excitatory neurotransmitter. In the CNS, besides its primary signaling function, glutamate is also at the crossroad of metabolic and neurotransmitter pathways. Importance of brain GDH...... was questioned here by generation of CNS-specific GDH-null mice (CnsGlud1(-/-)); which were viable, fertile and without apparent behavioral problems. GDH immunoreactivity as well as enzymatic activity were absent in Cns-Glud1(-/-) brains. Immunohistochemical analyses on brain sections revealed that the pyramidal...... oxidative catabolism of glutamate in astrocytes, showing that GDH is required for Krebs cycle pathway. As revealed by NMR studies, brain glutamate levels remained unchanged, whereas glutamine levels were increased. This pattern was favored by up-regulation of astrocyte-type glutamate and glutamine...

  16. Synaptic glutamate spillover increases NMDA receptor reliability at the cerebellar glomerulus

    OpenAIRE

    Mitchell, Cassie S.; Lee, Robert H.

    2011-01-01

    Glutamate spillover in the mossy fiber to granule cell cerebellar glomeruli has been hypothesized to increase neurotransmission reliability. In this study, we evaluate this hypothesis using an experimentally-based quantitative model of glutamate spillover on the N-methyl-d-aspartate receptors (NMDA-Rs) at the cerebellar glomerulus. The transient and steady-state responses of NMDA-Rs were examined over a physiological range of firing rates. Examined cases included direct glutamate release acti...

  17. Cleft Lip and Cleft Palate

    Science.gov (United States)

    ... health conditions > Cleft lip and cleft palate Cleft lip and cleft palate E-mail to a friend Please fill in ... repair cleft lip and palate. What are cleft lip and cleft palate? Cleft lip is a birth defect in which ...

  18. Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.

    Science.gov (United States)

    Beccano-Kelly, Dayne A; Kuhlmann, Naila; Tatarnikov, Igor; Volta, Mattia; Munsie, Lise N; Chou, Patrick; Cao, Li-Ping; Han, Heather; Tapia, Lucia; Farrer, Matthew J; Milnerwood, Austen J

    2014-01-01

    Mutations in Leucine-Rich Repeat Kinase-2 (LRRK2) result in familial Parkinson's disease and the G2019S mutation alone accounts for up to 30% in some ethnicities. Despite this, the function of LRRK2 is largely undetermined although evidence suggests roles in phosphorylation, protein interactions, autophagy and endocytosis. Emerging reports link loss of LRRK2 to altered synaptic transmission, but the effects of the G2019S mutation upon synaptic release in mammalian neurons are unknown. To assess wild type and mutant LRRK2 in established neuronal networks, we conducted immunocytochemical, electrophysiological and biochemical characterization of >3 week old cortical cultures of LRRK2 knock-out, wild-type overexpressing and G2019S knock-in mice. Synaptic release and synapse numbers were grossly normal in LRRK2 knock-out cells, but discretely reduced glutamatergic activity and reduced synaptic protein levels were observed. Conversely, synapse density was modestly but significantly increased in wild-type LRRK2 overexpressing cultures although event frequency was not. In knock-in cultures, glutamate release was markedly elevated, in the absence of any change to synapse density, indicating that physiological levels of G2019S LRRK2 elevate probability of release. Several pre-synaptic regulatory proteins shown by others to interact with LRRK2 were expressed at normal levels in knock-in cultures; however, synapsin 1 phosphorylation was significantly reduced. Thus, perturbations to the pre-synaptic release machinery and elevated synaptic transmission are early neuronal effects of LRRK2 G2019S. Furthermore, the comparison of knock-in and overexpressing cultures suggests that one copy of the G2019S mutation has a more pronounced effect than an ~3-fold increase in LRRK2 protein. Mutant-induced increases in transmission may convey additional stressors to neuronal physiology that may eventually contribute to the pathogenesis of Parkinson's disease.

  19. Early-life seizures alter synaptic calcium-permeable AMPA receptor function and plasticity

    Science.gov (United States)

    Lippman-Bell, Jocelyn J.; Zhou, Chengwen; Sun, Hongyu; Feske, Joel S.; Jensen, Frances E.

    2016-01-01

    Calcium (Ca2+)-mediated1 signaling pathways are critical to synaptic plasticity. In adults, the NMDA glutamate receptor (NMDAR) represents a major route for activity-dependent synaptic Ca2+ entry. However, during neonatal development, when synaptic plasticity is high, many AMPA glutamate receptors (AMPARs) are also permeable to Ca2+ (CP-AMPAR) due to low GluA2 subunit expression, providing an additional route for activity- and glutamate-dependent Ca2+ influx and subsequent signaling. Therefore, altered hippocampal Ca2+ signaling may represent an age-specific pathogenic mechanism. We thus aimed to assess Ca2+ responses 48 hours after hypoxia-induced neonatal seizures (HS) in postnatal day (P)10 rats, a post-seizure time point at which we previously reported LTP attenuation. We found that Ca2+ responses were higher in brain slices from post-HS rats than in controls and this increase was CP-AMPAR-dependent. To determine whether synaptic CP-AMPAR expression was also altered post-HS, we assessed the expression of GluA2 at hippocampal synapses and the expression of long-term depression (LTD), which has been linked to the presence of synaptic GluA2. Here we report a decrease 48 hours after HS in synaptic GluA2 expression at synapses and LTD in hippocampal CA1. Given the potentially critical role of AMPAR trafficking in disease progression, we aimed to establish whether post-seizure in vivo AMPAR antagonist treatment prevented the enhanced Ca2+ responses, changes in GluA2 synaptic expression, and diminished LTD. We found that NBQX treatment prevents all three of these post-seizure consequences, further supporting a critical role for AMPARs as an age-specific therapeutic target. PMID:27521497

  20. GMP reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats.

    Science.gov (United States)

    Rubin, M A; Jurach, A; da Costa Júnior, E M; Lima, T T; Jiménez-Bernal, R E; Begnini, J; Souza, D O; de Mello, C F

    1996-09-02

    Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.

  1. Long-term culture of astrocytes attenuates the readily releasable pool of synaptic vesicles.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kawano

    Full Text Available The astrocyte is a major glial cell type of the brain, and plays key roles in the formation, maturation, stabilization and elimination of synapses. Thus, changes in astrocyte condition and age can influence information processing at synapses. However, whether and how aging astrocytes affect synaptic function and maturation have not yet been thoroughly investigated. Here, we show the effects of prolonged culture on the ability of astrocytes to induce synapse formation and to modify synaptic transmission, using cultured autaptic neurons. By 9 weeks in culture, astrocytes derived from the mouse cerebral cortex demonstrated increases in β-galactosidase activity and glial fibrillary acidic protein (GFAP expression, both of which are characteristic of aging and glial activation in vitro. Autaptic hippocampal neurons plated on these aging astrocytes showed a smaller amount of evoked release of the excitatory neurotransmitter glutamate, and a lower frequency of miniature release of glutamate, both of which were attributable to a reduction in the pool of readily releasable synaptic vesicles. Other features of synaptogenesis and synaptic transmission were retained, for example the ability to induce structural synapses, the presynaptic release probability, the fraction of functional presynaptic nerve terminals, and the ability to recruit functional AMPA and NMDA glutamate receptors to synapses. Thus the presence of aging astrocytes affects the efficiency of synaptic transmission. Given that the pool of readily releasable vesicles is also small at immature synapses, our results are consistent with astrocytic aging leading to retarded synapse maturation.

  2. Different metabotropic glutamate receptors play opposite roles in synaptic plasticity of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, Silvarosa; Frondaroli, Adele; Pettorossi, Vito Enrico

    2002-09-15

    In the medial vestibular nuclei (MVN) of rat brainstem slices, the role of group II and III metabotropic glutamate receptors (mGluRs) and of the subtypes of group I mGluRs: mGluR1, mGluR5, was investigated in basal synaptic transmission and in the induction and maintenance of long-term potentiation (LTP). We used selective antagonists and agonists for mGluRs and we analysed the field potentials evoked by vestibular afferent stimulation before and after high-frequency stimulation (HFS) to induce LTP. The group II and III mGluR antagonist, (R,S)-alpha-2-methyl-4sulphonophenylglycine (MSPG), induced LTP per se and caused a reduction of the paired-pulse facilitation (PPF) ratio indicating an enhancement of glutamate release. This suggests that group II and III mGluRs are activated under basal conditions to limit glutamate release. Both the group II and III mGluR selective antagonists, 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoate (LY341495) and (R,S)-alpha-methylserine-O-phosphate (MSOP), induced LTP, and the selective agonists, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed the field potentials and prevented HFS-LTP, with a prevailing contribution of group II mGluRs over that of group III mGluRs. The mGluR1 antagonist, 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) prevented the full development and maintenance of HFS-LTP. By contrast, the mGluR5 antagonist, 2-methyl-6-phenylethynylpyridine (MPEP) induced LTP per se, which was impeded by CPCCOEt, and it had no effect on LTP once induced by HFS. The PPF analysis showed an enhancement of glutamate release during MPEP potentiation. The group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced LTP per se, which was blocked by CPCCOEt. By contrast the mGluR5 agonist, (R,S)-2-chloro-5-hydroxypheylglycine (CHPG) prevented LTP elicited by HFS and DHPG as well. In conclusion vestibular LTP is

  3. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

    International Nuclear Information System (INIS)

    Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

    2014-01-01

    Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

  4. Role of group II metabotropic glutamate receptors 2/3 and group I metabotropic glutamate receptor 5 in developing rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, Silvarosa; Frondaroli, Adele; Pettorossi, Vito Enrico

    2005-08-22

    In brainstem slices from developing rats, metabotropic glutamate receptors mGluR2/3 and mGluR5 play different inhibitory roles in synaptic transmission and plasticity of the medial vestibular nuclei. The mGluR2/3 block (LY341495) reduces the occurrence of long-term depression after vestibular afferent high frequency stimulation at P8-P10, and increases that of long-term potentiation, while the mGluR5 block prevents high frequency stimulation long-term depression. Later on, the receptor block does not influence high frequency stimulation effects. In addition, while mGluR2/3 agonist (APDC) always provokes a transient reduction of synaptic responses, that of mGluR5 (CHPG) induces long-term depression per se at P8-P10. These results show a key role of mGluR5 in inducing high frequency stimulation long-term depression in developing medial vestibular nuclei, while mGluR2/3 modulate synaptic transmission, probably through presynaptic control of glutamate release.

  5. Activation of Phosphatidylinositol-Linked Dopamine Receptors Induces a Facilitation of Glutamate-Mediated Synaptic Transmission in the Lateral Entorhinal Cortex.

    Directory of Open Access Journals (Sweden)

    Iulia Glovaci

    Full Text Available The lateral entorhinal cortex receives strong inputs from midbrain dopamine neurons that can modulate its sensory and mnemonic function. We have previously demonstrated that 1 µM dopamine facilitates synaptic transmission in layer II entorhinal cortex cells via activation of D1-like receptors, increased cAMP-PKA activity, and a resulting enhancement of AMPA-receptor mediated currents. The present study assessed the contribution of phosphatidylinositol (PI-linked D1 receptors to the dopaminergic facilitation of transmission in layer II of the rat entorhinal cortex, and the involvement of phospholipase C activity and release of calcium from internal stores. Whole-cell patch-clamp recordings of glutamate-mediated evoked excitatory postsynaptic currents were obtained from pyramidal and fan cells. Activation of D1-like receptors using SKF38393, SKF83959, or 1 µM dopamine induced a reversible facilitation of EPSCs which was abolished by loading cells with either the phospholipase C inhibitor U-73122 or the Ca2+ chelator BAPTA. Neither the L-type voltage-gated Ca2+ channel blocker nifedipine, nor the L/N-type channel blocker cilnidipine, blocked the facilitation of synaptic currents. However, the facilitation was blocked by blocking Ca2+ release from internal stores via inositol 1,4,5-trisphosphate (InsP3 receptors or ryanodine receptors. Follow-up studies demonstrated that inhibiting CaMKII activity with KN-93 failed to block the facilitation, but that application of the protein kinase C inhibitor PKC(19-36 completely blocked the dopamine-induced facilitation. Overall, in addition to our previous report indicating a role for the cAMP-PKA pathway in dopamine-induced facilitation of synaptic transmission, we demonstrate here that the dopaminergic facilitation of synaptic responses in layer II entorhinal neurons also relies on a signaling cascade dependent on PI-linked D1 receptors, PLC, release of Ca2+ from internal stores, and PKC activation which is

  6. Co-release of glutamate and GABA from single vesicles in GABAergic neurons exogenously expressing VGLUT3

    Directory of Open Access Journals (Sweden)

    Johannes eZimmermann

    2015-09-01

    Full Text Available The identity of the vesicle neurotransmitter transporter expressed by a neuron largely corresponds with the primary neurotransmitter that cell releases. However, the vesicular glutamate transporter subtype 3 (VGLUT3 is mainly expressed in non-glutamatergic neurons, including cholinergic, serotonergic, or GABAergic neurons. Though a functional role for glutamate release from these non-glutamatergic neurons has been demonstrated, the interplay between VGLUT3 and the neuron’s characteristic neurotransmitter transporter, particularly in the case of GABAergic neurons, at the synaptic and vesicular level is less clear. In this study, we explore how exogenous expression of VGLUT3 in striatal GABAergic neurons affects the packaging and release of glutamate and GABA in synaptic vesicles. We found that VGLUT3 expression in isolated, autaptic GABAergic neurons leads to action potential evoked release of glutamate. Under these conditions, glutamate and GABA could be packaged together in single vesicles release either spontaneously or asynchronously. However, the presence of glutamate in GABAergic vesicles did not affect uptake of GABA itself, suggesting a lack of synergy in vesicle filling for these transmitters. Finally, we found postsynaptic detection of glutamate released from GABAergic terminals difficult when bona fide glutamatergic synapses were present, suggesting that co-released glutamate cannot induce postsynaptic glutamate receptor clustering.

  7. Glutamate and Brain Glutaminases in Drug Addiction.

    Science.gov (United States)

    Márquez, Javier; Campos-Sandoval, José A; Peñalver, Ana; Matés, José M; Segura, Juan A; Blanco, Eduardo; Alonso, Francisco J; de Fonseca, Fernando Rodríguez

    2017-03-01

    Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction. Glutaminases are the main glutamate-producing enzymes in brain and dysregulation of their function have been associated with neurodegenerative diseases and neurological disorders; however, the possible implication of these enzymes in drug addiction remains largely unknown. This mini-review focuses on brain glutaminase isozymes and their alterations by in vivo exposure to drugs of abuse, which are discussed in the context of the glutamate homeostasis theory of addiction. Recent findings from mouse models have shown that drugs induce changes in the expression profiles of key glutamatergic transmission genes, although the molecular mechanisms that regulate drug-induced neuronal sensitization and behavioral plasticity are not clear.

  8. Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular Glutamate Transporter

    Directory of Open Access Journals (Sweden)

    Julia Preobraschenski

    2018-04-01

    Full Text Available Summary: Vesicular glutamate transporters (VGLUTs fill synaptic vesicles with glutamate and are thus essential for glutamatergic neurotransmission. However, VGLUTs were originally discovered as members of a transporter subfamily specific for inorganic phosphate (Pi. It is still unclear how VGLUTs accommodate glutamate transport coupled to an electrochemical proton gradient ΔμH+ with inversely directed Pi transport coupled to the Na+ gradient and the membrane potential. Using both functional reconstitution and heterologous expression, we show that VGLUT transports glutamate and Pi using a single substrate binding site but different coupling to cation gradients. When facing the cytoplasm, both ions are transported into synaptic vesicles in a ΔμH+-dependent fashion, with glutamate preferred over Pi. When facing the extracellular space, Pi is transported in a Na+-coupled manner, with glutamate competing for binding but at lower affinity. We conclude that VGLUTs have dual functions in both vesicle transmitter loading and Pi homeostasis within glutamatergic neurons. : Preobraschenski et al. show that the vesicular glutamate transporter functions as a bi-directional phosphate transporter that is coupled with different cations in each direction and hence may play a key role in neuronal phosphate homeostasis. Keywords: VGLUT, SLC17 family, type I Na+-dependent inorganic phosphate transporter, ATPase, proteoliposomes, hybrid vesicles, anti-VGLUT1 nanobody

  9. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A

    2000-01-01

    important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization......, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions...... and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K(+) current, cationic inward...

  10. Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

    Directory of Open Access Journals (Sweden)

    Christoph Straub

    2016-07-01

    Full Text Available Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

  11. Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

    Science.gov (United States)

    2012-01-01

    Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners. PMID:22852823

  12. Facts about Cleft Lip and Cleft Palate

    Science.gov (United States)

    ... Information For… Media Policy Makers Facts about Cleft Lip and Cleft Palate Language: English (US) Español (Spanish) Recommend on Facebook ... can make referrals to cleft/craniofacial treatment teams. Cleft Lip & Palate Foundation of Smiles Cleft Lip & Palate Foundation of ...

  13. A Ca2+-based computational model for NDMA receptor-dependent synaptic plasticity at individual post-synaptic spines in the hippocampus

    Directory of Open Access Journals (Sweden)

    Owen Rackham

    2010-07-01

    Full Text Available Associative synaptic plasticity is synapse specific and requires coincident activity in presynaptic and postsynaptic neurons to activate NMDA receptors (NMDARs. The resultant Ca2+ influx is the critical trigger for the induction of synaptic plasticity. Given its centrality for the induction of synaptic plasticity, a model for NMDAR activation incorporating the timing of presynaptic glutamate release and postsynaptic depolarization by back-propagating action potentials could potentially predict the pre- and post-synaptic spike patterns required to induce synaptic plasticity. We have developed such a model by incorporating currently available data on the timecourse and amplitude of the postsynaptic membrane potential within individual spines. We couple this with data on the kinetics of synaptic NMDARs and then use the model to predict the continuous spine [Ca2+] in response to regular or irregular pre- and post-synaptic spike patterns. We then incorporate experimental data from synaptic plasticity induction protocols by regular activity patterns to couple the predicted local peak [Ca2+] to changes in synaptic strength. We find that our model accurately describes [Ca2+] in dendritic spines resulting from NMDAR activation during presynaptic and postsynaptic activity when compared to previous experimental observations. The model also replicates the experimentally determined plasticity outcome of regular and irregular spike patterns when applied to a single synapse. This model could therefore be used to predict the induction of synaptic plasticity under a variety of experimental conditions and spike patterns.

  14. Regulation of dopamine D1 receptor dynamics within the postsynaptic density of hippocampal glutamate synapses.

    Directory of Open Access Journals (Sweden)

    Laurent Ladepeche

    Full Text Available Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signalling interplay at glutamate synapse remain poorly understood. Among the cellular mechanisms proposed to aggregate D1R in glutamate synapses, the direct interaction between D1R and the scaffold protein PSD95 or the direct interaction with the glutamate NMDA receptor (NMDAR have been proposed. To tackle this question we here used high-resolution single nanoparticle imaging since it provides a powerful way to investigate at the sub-micron resolution the dynamic interaction between these partners in live synapses. We demonstrate in hippocampal neuronal networks that dopamine D1 receptors (D1R laterally diffuse within glutamate synapses, in which their diffusion is reduced. Disrupting the interaction between D1R and PSD95, through genetical manipulation and competing peptide, did not affect D1R dynamics in glutamatergic synapses. However, preventing the physical interaction between D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of diffusing D1R. Together, these data provide direct evidence that the interaction between D1R and NMDAR in synapses participate in the building of the dopamine-receptor-mediated signalling, and most likely to the glutamate-dopamine cross-talk.

  15. A neuroprotective role for microRNA miR-1000 mediated by limiting glutamate excitotoxicity

    DEFF Research Database (Denmark)

    Verma, Pushpa; Augustine, George J; Ammar, Mohamed-Raafet

    2015-01-01

    Evidence has begun to emerge for microRNAs as regulators of synaptic signaling, specifically acting to control postsynaptic responsiveness during synaptic transmission. In this report, we provide evidence that Drosophila melanogaster miR-1000 acts presynaptically to regulate glutamate release at ...... a neuroprotective function in the brains of flies and mice. Drosophila miR-1000 showed activity-dependent expression, which might serve as a mechanism to allow neuronal activity to fine-tune the strength of excitatory synaptic transmission....

  16. Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry.

    Science.gov (United States)

    Mattson, M P; Lee, R E; Adams, M E; Guthrie, P B; Kater, S B

    1988-11-01

    A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D-glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry.

  17. Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

    Science.gov (United States)

    Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

    2017-09-09

    In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

  18. Clefting of the Alveolus: Emphasizing the Distinction from Cleft Palate.

    Science.gov (United States)

    Wirtz, Nicholas; Sidman, James; Block, William

    2016-05-01

    Oral clefting is one of the most common significant fetal abnormalities. Cleft lip and cleft palate have drastically different clinical ramifications and management from one another. A cleft of the alveolus (with or without cleft lip) can confuse the diagnostic picture and lead to a false assumption of cleft palate. The cleft alveolus should be viewed on the spectrum of cleft lip rather than be associated with cleft palate. This is made evident by understanding the embryological development of the midface and relevant terminology. Cleft alveolus carries significantly different clinical implications and treatment options than that of cleft palate. Accurately distinguishing cleft alveolus from cleft palate is crucial for appropriate discussions regarding the patient's care. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    Science.gov (United States)

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; pagmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Beech, Robin N.; Lalande, Maryline J.

    2015-01-01

    that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream......Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed......, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling....

  1. The SOL-2/Neto auxiliary protein modulates the function of AMPA-subtype ionotropic glutamate receptors.

    Science.gov (United States)

    Wang, Rui; Mellem, Jerry E; Jensen, Michael; Brockie, Penelope J; Walker, Craig S; Hoerndli, Frédéric J; Hauth, Linda; Madsen, David M; Maricq, Andres V

    2012-09-06

    The neurotransmitter glutamate mediates excitatory synaptic transmission by gating ionotropic glutamate receptors (iGluRs). AMPA receptors (AMPARs), a subtype of iGluR, are strongly implicated in synaptic plasticity, learning, and memory. We previously discovered two classes of AMPAR auxiliary proteins in C. elegans that modify receptor kinetics and thus change synaptic transmission. Here, we have identified another auxiliary protein, SOL-2, a CUB-domain protein that associates with both the related auxiliary subunit SOL-1 and with the GLR-1 AMPAR. In sol-2 mutants, behaviors dependent on glutamatergic transmission are disrupted, GLR-1-mediated currents are diminished, and GLR-1 desensitization and pharmacology are modified. Remarkably, a secreted variant of SOL-1 delivered in trans can rescue sol-1 mutants, and this rescue depends on in cis expression of SOL-2. Finally, we demonstrate that SOL-1 and SOL-2 have an ongoing role in the adult nervous system to control AMPAR-mediated currents. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Soluble ectodomain of neuroligin 1 decreases synaptic activity by activating metabotropic glutamate receptor 2

    DEFF Research Database (Denmark)

    Gjørlund, Michelle D.; Carlsen, Eva Maria Meier; Kønig, Andreas Bay

    2017-01-01

    Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent ...

  3. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

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    Mario U Manto

    2015-03-01

    Full Text Available Autoantibodies to the smaller isoform of glutamate decarboxylase can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct glutamate decarboxylase autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal glutamate decarboxylase antibodies. We found that glutamate decarboxylase autoantibodies present in patients with stiff person syndrome (n = 7 and cerebellar ataxia (n = 15 recognized an epitope distinct from that recognized by glutamate decarboxylase autoantibodies present in patients with type 1 diabetes mellitus (n = 10 or limbic encephalitis (n = 4. We demonstrated that the administration of a monoclonal glutamate decarboxylase antibody representing this epitope specificity (1 disrupted in vitro the association of glutamate decarboxylase with γ-Aminobutyric acid containing synaptic vesicles, (2 depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect, (3 significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task, (4 markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm, and (5 induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of glutamate decarboxylase by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such glutamate decarboxylase antibodies could be envisioned.

  4. The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures.

    Science.gov (United States)

    Mayer, Mark L

    2017-11-21

    Ion channels activated by glutamate mediate excitatory synaptic transmission in the central nervous system. Similar to other ligand-gated ion channels, their gating cycle begins with transitions from a ligand-free closed state to glutamate-bound active and desensitized states. In an attempt to reveal the molecular mechanisms underlying gating, numerous structures for glutamate receptors have been solved in complexes with agonists, antagonists, allosteric modulators, and auxiliary proteins. The embarrassingly rich library of structures emerging from this work reveals very dynamic molecules with a more complex conformational spectrum than anticipated from functional studies. Unanticipated conformations solved for complexes with competitive antagonists and a lack of understanding of the structural basis for ion channel subconductance states further highlight challenges that have yet to be addressed. Published by Elsevier Inc.

  5. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons.

    Science.gov (United States)

    Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

    2006-10-01

    Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-beta-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

  6. Patterns of Cleft Lip and Cleft Palate in Northern Pakistan

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    Mansoor Khan

    2012-04-01

    Results: A total of 159 patients of cleft lip and cleft palate deformities were included in the study, having a mean age of 3.5+6.59 years and containing 59.1% males and 40.9% females with a ratio of 1.4:1. A cleft lip with palate, cleft palate and cleft lip were found in 51.6%, 31.4% and 17% of cases, respectively. Left-sided clefts were most common in the cleft lip with palate and the isolated cleft lip deformity. A cleft lip with palate was a male dominant variety (62.8% of cases, while in the cleft palate variety, the dominant gender was female. In 61.6% of cases, the parent had a consanguineous relationship. In 21.4% of cases, family history was positive for the cleft lip/palate. Other congenital anomalies were associated in 10.7% of cases. Conclusion: Cleft deformities of the lip and palate affect the male population more than females with cleft lips, in association with a cleft palate being the most common anomaly. Females are mainly affected by an isolated cleft palate. The high prevalence of these deformities in consanguineous marriages emphasizes educating people. The lower number of patients from distant distracts of Northern Pakistan calls for the attention of the health department. [Arch Clin Exp Surg 2012; 1(2.000: 63-70

  7. Synaptic proteins and receptors defects in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Jianling eChen

    2014-09-01

    Full Text Available Recent studies have found that hundreds of genetic variants, including common and rare variants, rare and de novo mutations, and common polymorphisms have contributed to the occurrence of autism spectrum disorders (ASDs. The mutations in a number of genes such as neurexin, neuroligin, postsynaptic density protein 95 (PSD-95, SH3 and multiple ankyrin repeat domains 3 (SHANK3, synapsin, gephyrin, cadherin (CDH and protocadherin (PCDH, thousand-and-one-amino acid 2 kinase (TAOK2, and contactin (CNTN, have been shown to play important roles in the development and function of synapses. In addition, synaptic receptors, such as gamma-aminobutyric acid (GABA receptors and glutamate receptors, have also been associated with ASDs. This review will primarily focus on the defects of synaptic proteins and receptors associated with ASDs and their roles in the pathogenesis of ASDs via synaptic pathways.

  8. Biphasic synaptic Ca influx arising from compartmentalized electrical signals in dendritic spines.

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    Brenda L Bloodgood

    2009-09-01

    Full Text Available Excitatory synapses on mammalian principal neurons are typically formed onto dendritic spines, which consist of a bulbous head separated from the parent dendrite by a thin neck. Although activation of voltage-gated channels in the spine and stimulus-evoked constriction of the spine neck can influence synaptic signals, the contribution of electrical filtering by the spine neck to basal synaptic transmission is largely unknown. Here we use spine and dendrite calcium (Ca imaging combined with 2-photon laser photolysis of caged glutamate to assess the impact of electrical filtering imposed by the spine morphology on synaptic Ca transients. We find that in apical spines of CA1 hippocampal neurons, the spine neck creates a barrier to the propagation of current, which causes a voltage drop and results in spatially inhomogeneous activation of voltage-gated Ca channels (VGCCs on a micron length scale. Furthermore, AMPA and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively that are colocalized on individual spine heads interact to produce two kinetically and mechanistically distinct phases of synaptically evoked Ca influx. Rapid depolarization of the spine triggers a brief and large Ca current whose amplitude is regulated in a graded manner by the number of open AMPARs and whose duration is terminated by the opening of small conductance Ca-activated potassium (SK channels. A slower phase of Ca influx is independent of AMPAR opening and is determined by the number of open NMDARs and the post-stimulus potential in the spine. Biphasic synaptic Ca influx only occurs when AMPARs and NMDARs are coactive within an individual spine. These results demonstrate that the morphology of dendritic spines endows associated synapses with specialized modes of signaling and permits the graded and independent control of multiple phases of synaptic Ca influx.

  9. Glutamate neurotransmission is affected in prenatally stressed offspring

    DEFF Research Database (Denmark)

    Adrover, Ezequiela; Pallarés, Maria Eugenia; Baier, Carlos Javier

    2015-01-01

    Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization with syn......Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization...... with synaptic loss. Since metabolism of glutamate is dependent on interactions between neurons and surrounding astroglia, our results suggest that glutamate neurotransmitter pathways might be impaired in the brain of prenatally stressed rats. To study the effect of prenatal stress on the metabolism...... was not affected it was found that prenatal stress (PS) changed the expression of the transporters, thus, producing a higher level of vesicular vGluT-1 in the frontal cortex (FCx) and elevated levels of GLT1 protein and messenger RNA in the hippocampus (HPC) of adult male PS offspring. We also observed increased...

  10. Hebbian Plasticity Guides Maturation of Glutamate Receptor Fields In Vivo

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    Dmitrij Ljaschenko

    2013-05-01

    Full Text Available Synaptic plasticity shapes the development of functional neural circuits and provides a basis for cellular models of learning and memory. Hebbian plasticity describes an activity-dependent change in synaptic strength that is input-specific and depends on correlated pre- and postsynaptic activity. Although it is recognized that synaptic activity and synapse development are intimately linked, our mechanistic understanding of the coupling is far from complete. Using Channelrhodopsin-2 to evoke activity in vivo, we investigated synaptic plasticity at the glutamatergic Drosophila neuromuscular junction. Remarkably, correlated pre- and postsynaptic stimulation increased postsynaptic sensitivity by promoting synapse-specific recruitment of GluR-IIA-type glutamate receptor subunits into postsynaptic receptor fields. Conversely, GluR-IIA was rapidly removed from synapses whose activity failed to evoke substantial postsynaptic depolarization. Uniting these results with developmental GluR-IIA dynamics provides a comprehensive physiological concept of how Hebbian plasticity guides synaptic maturation and sparse transmitter release controls the stabilization of the molecular composition of individual synapses.

  11. Intracellular Na+ concentration influences short-term plasticity of glutamate transporter-mediated currents in neocortical astrocytes.

    Science.gov (United States)

    Unichenko, Petr; Myakhar, Olga; Kirischuk, Sergei

    2012-04-01

    Fast synaptic transmission requires a rapid clearance of the released neurotransmitter from the extracellular space. Glial glutamate transporters (excitatory amino acid transporters, EAATs) strongly contribute to glutamate removal. In this work, we investigated the paired-pulse plasticity of synaptically activated, glutamate transporter-mediated currents (STCs) in cortical layer 2/3 astrocytes. STCs were elicited by local electrical stimulation in layer 4 in the presence of ionotropic glutamate (AMPA and NMDA), GABAA, and GABAB receptor antagonists. In experiments with low [Na(+)]i (5 mM) intrapipette solution, STCs elicited by paired-pulse stimulation demonstrated paired-pulse facilitation (PPF) at short (astrocytic [Na(+)]i, reduced the mean STC amplitude, decreased PPF at short ISIs, and slowed STC kinetics. All GABA-induced changes were blocked by NO-711 and SNAP-5114, GABA transporter (GATs) antagonists. In experiments with the low intrapipette solution, GAT blockade under control conditions decreased PPF at short ISIs both at room and at near physiological temperatures. Dialysis of single astrocyte with low [Na(+)]i solution increased the amplitude and reduced PPR of evoked field potentials recorded in the vicinity of the astrocyte. We conclude that (1) endogenous GABA via GATs may influence EAAT functioning and (2) astrocytic [Na(+)]i modulates the short-term plasticity of STCs and in turn the efficacy of glutamate removal. Copyright © 2012 Wiley Periodicals, Inc.

  12. Defective glycinergic synaptic transmission in zebrafish motility mutants

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    Hiromi Hirata

    2010-01-01

    Full Text Available Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs.

  13. Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

    Science.gov (United States)

    Hirata, Hiromi; Carta, Eloisa; Yamanaka, Iori; Harvey, Robert J.; Kuwada, John Y.

    2009-01-01

    Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho) mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch-once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch-once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs. PMID:20161699

  14. Cleft Lip and Cleft Palate

    Science.gov (United States)

    ... refers to a cleft in the lip only accounting for 20 percent of all clefts. What causes ... malformation of the upper airway can affect the function of the Eustachian tube and increase the possibility ...

  15. Cerebellar Kainate Receptor-Mediated Facilitation of Glutamate Release Requires Ca2+-Calmodulin and PKA

    Directory of Open Access Journals (Sweden)

    Rafael Falcón-Moya

    2018-06-01

    Full Text Available We elucidated the mechanisms underlying the kainate receptor (KAR-mediated facilitatory modulation of synaptic transmission in the cerebellum. In cerebellar slices, KA (3 μM increased the amplitude of evoked excitatory postsynaptic currents (eEPSCs at synapses between axon terminals of parallel fibers (PF and Purkinje neurons. KA-mediated facilitation was antagonized by NBQX under condition where AMPA receptors were previously antagonized. Inhibition of protein kinase A (PKA suppressed the effect of KA on glutamate release, which was also obviated by the prior stimulation of adenylyl cyclase (AC. KAR-mediated facilitation of synaptic transmission was prevented by blocking Ca2+ permeant KARs using philanthotoxin. Furthermore, depletion of intracellular Ca2+ stores by thapsigargin, or inhibition of Ca2+-induced Ca2+-release by ryanodine, abrogated the synaptic facilitation by KA. Thus, the KA-mediated modulation was conditional on extracellular Ca2+ entry through Ca2+-permeable KARs, as well as and mobilization of Ca2+ from intracellular stores. Finally, KAR-mediated facilitation was sensitive to calmodulin inhibitors, W-7 and calmidazolium, indicating that the increased cytosolic [Ca2+] sustaining KAR-mediated facilitation of synaptic transmission operates through a downstream Ca2+/calmodulin coupling. We conclude that, at cerebellar parallel fiber-Purkinje cell synapses, presynaptic KARs mediate glutamate release facilitation, and thereby enhance synaptic transmission through Ca2+-calmodulin dependent activation of adenylyl cyclase/cAMP/protein kinase A signaling.

  16. Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.

    Science.gov (United States)

    Ma, Qiu-Lan; Teng, Edmond; Zuo, Xiaohong; Jones, Mychica; Teter, Bruce; Zhao, Evan Y; Zhu, Cansheng; Bilousova, Tina; Gylys, Karen H; Apostolova, Liana G; LaDu, Mary Jo; Hossain, Mir Ahamed; Frautschy, Sally A; Cole, Gregory M

    2018-06-01

    Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7-8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4 +/+ /FAD +/- ) relative to E4FAD- (non-carrier; APOE4 +/+ /FAD -/- ) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD. Copyright © 2018. Published by Elsevier Inc.

  17. Differential splicing and glycosylation of Apoer2 alters synaptic plasticity and fear learning.

    Science.gov (United States)

    Wasser, Catherine R; Masiulis, Irene; Durakoglugil, Murat S; Lane-Donovan, Courtney; Xian, Xunde; Beffert, Uwe; Agarwala, Anandita; Hammer, Robert E; Herz, Joachim

    2014-11-25

    Apoer2 is an essential receptor in the central nervous system that binds to the apolipoprotein ApoE. Various splice variants of Apoer2 are produced. We showed that Apoer2 lacking exon 16, which encodes the O-linked sugar (OLS) domain, altered the proteolytic processing and abundance of Apoer2 in cells and synapse number and function in mice. In cultured cells expressing this splice variant, extracellular cleavage of OLS-deficient Apoer2 was reduced, consequently preventing γ-secretase-dependent release of the intracellular domain of Apoer2. Mice expressing Apoer2 lacking the OLS domain had increased Apoer2 abundance in the brain, hippocampal spine density, and glutamate receptor abundance, but decreased synaptic efficacy. Mice expressing a form of Apoer2 lacking the OLS domain and containing an alternatively spliced cytoplasmic tail region that promotes glutamate receptor signaling showed enhanced hippocampal long-term potentiation (LTP), a phenomenon associated with learning and memory. However, these mice did not display enhanced spatial learning in the Morris water maze, and cued fear conditioning was reduced. Reducing the expression of the mutant Apoer2 allele so that the abundance of the protein was similar to that of Apoer2 in wild-type mice normalized spine density, hippocampal LTP, and cued fear learning. These findings demonstrated a role for ApoE receptors as regulators of synaptic glutamate receptor activity and established differential receptor glycosylation as a potential regulator of synaptic function and memory. Copyright © 2014, American Association for the Advancement of Science.

  18. Displacement of DL-[3H]-2-amino-4-phosphonobutanoic acid ( [3H]APB) binding with methyl-substituted APB analogues and glutamate agonists

    International Nuclear Information System (INIS)

    Robinson, M.B.; Crooks, S.L.; Johnson, R.L.; Koerner, J.F.

    1985-01-01

    The binding of the excitatory amino acid antagonist DL-2-amino-4-phosphonobutanoic acid (DL-APB) to rat brain synaptic plasma membranes was characterized. As determined by Scatchard analysis, the binding was saturable and homogeneous with a Kd = 6.0 microM and Bmax = 380 pmol/mg of protein. The binding was dependent on the presence of Ca 2+ and Cl - ions and was diminished upon freezing. The association rate constant was 6.8 X 10(-3) microM -1 min -1 , and the dissociation rate constant was 2.0 X 10(-2) min -1 . The L isomers of APB, glutamate, and aspartate were more potent as displacers of APB binding than the D isomers. With the exception of kynurenic acid, all compounds examined in both systems were more potent as displacers of APB binding than as inhibitors of synaptic transmission. This difference in potency was most pronounced for agonists at dentate granule cells. L-Glutamate, D-glutamate, and L-glutamate tetrazole were between 140- and 7500-fold more potent as displacers of DL-APB binding than as inhibitors of synaptic transmission. D-2-Amino-5-phosphonopentanoic acid and alpha-methyl-APB were between 10- and 20-fold more potent as displacers of binding

  19. Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

    Science.gov (United States)

    Brew, Helen; Attwell, David

    1987-06-01

    Glutamate is taken up avidly by glial cells in the central nervous system1. Glutamate uptake may terminate the transmitter action of glutamate released from neurons1, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique2. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

  20. PRRT2: from Paroxysmal Disorders to Regulation of Synaptic Function.

    Science.gov (United States)

    Valtorta, Flavia; Benfenati, Fabio; Zara, Federico; Meldolesi, Jacopo

    2016-10-01

    In the past few years, proline-rich transmembrane protein (PRRT)2 has been identified as the causative gene for several paroxysmal neurological disorders. Recently, an important role of PRRT2 in synapse development and function has emerged. Knock down of the protein strongly impairs the formation of synaptic contacts and neurotransmitter release. At the nerve terminal, PRRT2 endows synaptic vesicle exocytosis with Ca 2+ sensitivity by interacting with proteins of the fusion complex and with the Ca 2+ sensors synaptotagmins (Syts). In the postsynaptic compartment, PRRT2 interacts with glutamate receptors. The study of PRRT2 and of its mutations may help in refining our knowledge of the process of synaptic transmission and elucidating the pathogenetic mechanisms leading to derangement of network function in paroxysmal disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. NPY gene transfer in the hippocampus attenuates synaptic plasticity and learning

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Kanter-Schlifke, Irene; Carli, Mirjana

    2008-01-01

    -mediated mechanisms. In addition, transgene NPY seems to be released during high frequency neuronal activity, leading to decreased glutamate release in excitatory synapses. Importantly, memory consolidation appears to be affected by the treatment. We found that long-term potentiation (LTP) in the CA1 area...... processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the intact brain does not affect basal synaptic transmission, but slightly alters short-term synaptic plasticity, most likely via NPY Y2 receptor....... Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory...

  2. The C1q complement family of synaptic organizers: not just complementary.

    Science.gov (United States)

    Yuzaki, Michisuke

    2017-08-01

    Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity. C1ql2 and C1ql3, released from mossy fibers, determine the synaptic localization of postsynaptic kainate receptors in the hippocampus. C1ql3 also regulates the formation of synapses between the basolateral amygdala and the prefrontal cortex. These findings indicate the diverse functions of C1q family proteins in various brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Structure and affinity of two bicyclic glutamate analogues at AMPA and kainate receptors

    DEFF Research Database (Denmark)

    Møllerud, Stine; Pinto, Andrea; Marconi, Laura

    2017-01-01

    Ionotropic glutamate receptors (iGluRs) are involved in most of the fast excitatory synaptic transmission in the central nervous system. These receptors are important for learning and memory formation, but are also involved in the development of diseases such as Alzheimer’s disease, epilepsy...

  4. Astrocytes mediate in vivo cholinergic-induced synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Marta Navarrete

    2012-02-01

    Full Text Available Long-term potentiation (LTP of synaptic transmission represents the cellular basis of learning and memory. Astrocytes have been shown to regulate synaptic transmission and plasticity. However, their involvement in specific physiological processes that induce LTP in vivo remains unknown. Here we show that in vivo cholinergic activity evoked by sensory stimulation or electrical stimulation of the septal nucleus increases Ca²⁺ in hippocampal astrocytes and induces LTP of CA3-CA1 synapses, which requires cholinergic muscarinic (mAChR and metabotropic glutamate receptor (mGluR activation. Stimulation of cholinergic pathways in hippocampal slices evokes astrocyte Ca²⁺ elevations, postsynaptic depolarizations of CA1 pyramidal neurons, and LTP of transmitter release at single CA3-CA1 synapses. Like in vivo, these effects are mediated by mAChRs, and this cholinergic-induced LTP (c-LTP also involves mGluR activation. Astrocyte Ca²⁺ elevations and LTP are absent in IP₃R2 knock-out mice. Downregulating astrocyte Ca²⁺ signal by loading astrocytes with BAPTA or GDPβS also prevents LTP, which is restored by simultaneous astrocyte Ca²⁺ uncaging and postsynaptic depolarization. Therefore, cholinergic-induced LTP requires astrocyte Ca²⁺ elevations, which stimulate astrocyte glutamate release that activates mGluRs. The cholinergic-induced LTP results from the temporal coincidence of the postsynaptic activity and the astrocyte Ca²⁺ signal simultaneously evoked by cholinergic activity. Therefore, the astrocyte Ca²⁺ signal is necessary for cholinergic-induced synaptic plasticity, indicating that astrocytes are directly involved in brain storage information.

  5. Synaptic activity regulates AMPA receptor trafficking through different recycling pathways

    Science.gov (United States)

    Zheng, Ning; Jeyifous, Okunola; Munro, Charlotte; Montgomery, Johanna M; Green, William N

    2015-01-01

    Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. In this study, we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites. DOI: http://dx.doi.org/10.7554/eLife.06878.001 PMID:25970033

  6. Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120

    International Nuclear Information System (INIS)

    Wang Zhuying; Pekarskaya, Olga; Bencheikh, Meryem; Chao Wei; Gelbard, Harris A.; Ghorpade, Anuja; Rothstein, Jeffrey D.; Volsky, David J.

    2003-01-01

    L-Glutamate is the major excitatory neurotransmitter in the brain. Astrocytes maintain low levels of synaptic glutamate by high-affinity uptake and defects in this function may lead to neuronal cell death by excitotoxicity. We tested the effects of HIV-1 and its envelope glycoprotein gp120 upon glutamate uptake and expression of glutamate transporters EAAT1 and EAAT2 in fetal human astrocytes in vitro. Astrocytes isolated from fetal tissues between 16 and 19 weeks of gestation expressed EAAT1 and EAAT2 RNA and proteins as detected by Northern blot analysis and immunoblotting, respectively, and the cells were capable of specific glutamate uptake. Exposure of astrocytes to HIV-1 or gp120 significantly impaired glutamate uptake by the cells, with maximum inhibition within 6 h, followed by gradual decline during 3 days of observation. HIV-1-infected cells showed a 59% reduction in V max for glutamate transport, indicating a reduction in the number of active transporter sites on the cell surface. Impaired glutamate transport after HIV-1 infection or gp120 exposure correlated with a 40-70% decline in steady-state levels of EAAT2 RNA and protein. EAAT1 RNA and protein levels were less affected. Treatment of astrocytes with tumor necrosis factor-α (TNF-α) decreased the expression of both EAAT1 and EAAT2, but neither HIV-1 nor gp120 were found to induce TNF-α production by astrocytes. These findings demonstrate that HIV-1 and gp120 induce transcriptional downmodulation of the EAAT2 transporter gene in human astrocytes and coordinately attenuate glutamate transport by the cells. Reduction of the ability of HIV-1-infected astrocytes to take up glutamate may contribute to the development of neurological disease

  7. [Molecular organization of glutamate-sensitive chemoexcitatory membranes of nerve cells. Comparative analysis of glutamate-binding membrane proteins from the cerebral cortex of rats and humans].

    Science.gov (United States)

    Dambinova, S A; Gorodinskiĭ, A I; Lekomtseva, T M; Koreshonkov, O N

    1987-10-01

    The kinetics of 3H-L-glutamate binding to human brain synaptic membranes revealed the existence of one type of binding sites with Kd and Vmax comparable with those for freshly isolated rat brain membranes. The fraction of glutamate-binding proteins (GBP) was shown to contain three components with Mr of 14, 60 and 280 kD whose stoichiometry is specific for human and rat brain. All fractions were found to bind the radiolabeled neurotransmitter and to dissociate into subunits with Mr of 14 kD after treatment with-potent detergents (with the exception of the 56-60 kD component). Study of association-dissociation of GBP protein subunits by high performance liquid chromatography confirmed the hypothesis on the oligomeric structure of glutamate receptors which are made up of low molecular weight glycoprotein-lipid subunits and which form ionic channels by way of repeated association. Despite the similarity of antigen determinants in the active center of glutamate receptors from human and rat brain, it was assumed that the stoichiometry of structural organization of receptor subunits isolated from different sources is different. The functional role of structural complexity of human brain glutamate receptors is discussed.

  8. The Structure of Neurexin 1[alpha] Reveals Features Promoting a Role as Synaptic Organizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fang; Venugopal, Vandavasi; Murray, Beverly; Rudenko, Gabby (Michigan)

    2014-10-02

    {alpha}-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The {alpha}-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how {alpha}-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1{alpha} extracellular domain (n1{alpha}) to 2.65 {angstrom}. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 {angstrom} structure of n1{alpha} carrying splice insert SS3 in LNS4 reveals that SS3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables {alpha}-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

  9. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H; Skytt, Dorte M; Waagepetersen, Helle S

    2015-12-01

    Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids. © 2015 Wiley Periodicals, Inc.

  10. Synaptic activity and bioenergy homeostasis: implications in brain trauma and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Natasha eKhatri

    2013-12-01

    Full Text Available Powered by glucose metabolism, the brain is the most energy-demanding organ in our body, accounting for a quarter of total oxygen consumption. Adequate ATP production and regulation of the metabolic processes are essential for the maintenance of synaptic transmission and neuronal function. Glutamatergic synaptic activity utilizes the largest portion of bioenergy for synaptic events including neurotransmitter synthesis, vesicle recycling, and most importantly the postsynaptic activities leading to channel activation and rebalancing of ionic gradients. Bioenergy homeostasis is coupled with synaptic function via activities of the sodium pumps, glutamate transporters, glucose transport and mitochondria translocation. Energy insufficiency will be sensed by the AMP-activated dependent protein kinase (AMPK, a master metabolic regulator that stimulates the catalytic process to enhance energy production. A decline in energy supply and a disruption in bioenergy homeostasis play a critical role in multiple neuropathological conditions including ischemia, stroke and neurodegenerative diseases including Alzheimer’s disease and traumatic brain injuries.

  11. Localization of Presynaptic Plasticity Mechanisms Enables Functional Independence of Synaptic and Ectopic Transmission in the Cerebellum

    Directory of Open Access Journals (Sweden)

    Katharine L. Dobson

    2015-01-01

    Full Text Available In the cerebellar molecular layer parallel fibre terminals release glutamate from both the active zone and from extrasynaptic “ectopic” sites. Ectopic release mediates transmission to the Bergmann glia that ensheathe the synapse, activating Ca2+-permeable AMPA receptors and glutamate transporters. Parallel fibre terminals exhibit several forms of presynaptic plasticity, including cAMP-dependent long-term potentiation and endocannabinoid-dependent long-term depression, but it is not known whether these presynaptic forms of long-term plasticity also influence ectopic transmission to Bergmann glia. Stimulation of parallel fibre inputs at 16 Hz evoked LTP of synaptic transmission, but LTD of ectopic transmission. Pharmacological activation of adenylyl cyclase by forskolin caused LTP at Purkinje neurons, but only transient potentiation at Bergmann glia, reinforcing the concept that ectopic sites lack the capacity to express sustained cAMP-dependent potentiation. Activation of mGluR1 caused depression of synaptic transmission via retrograde endocannabinoid signalling but had no significant effect at ectopic sites. In contrast, activation of NMDA receptors suppressed both synaptic and ectopic transmission. The results suggest that the signalling mechanisms for presynaptic LTP and retrograde depression by endocannabinoids are restricted to the active zone at parallel fibre synapses, allowing independent modulation of synaptic transmission to Purkinje neurons and ectopic transmission to Bergmann glia.

  12. Cleft Lip and Palate

    Science.gov (United States)

    Cleft lip and cleft palate are birth defects that occur when a baby's lip or mouth do not form properly. They happen early during ... A baby can have a cleft lip, a cleft palate, or both. A cleft lip happens if the ...

  13. Unilateral Cleft Hand with Cleft Foot

    Science.gov (United States)

    Baba, Asif Nazir; Bhat, Yasmeen J.; Ahmed, Sheikh Mushtaq; Nazir, Abid

    2009-01-01

    Congenital anomalies of the hand form an important class of congenital malformations. They have a huge functional importance because of the part played by the hand in the daily activities of a person. The deformities also have significant cosmetic significance and may also be associated with other anomalies. Amongst the congenital anomalies, central deficiency or cleft hand is relatively rare. The association of cleft foot with cleft hand is an even more rare occurance. We present a case report of a 6 year old child, born of a non-consanginous marriage, having congenital central deficiency of ipsilateral hand and foot. PMID:21475543

  14. Psychological issues in cleft lip and cleft palate

    Directory of Open Access Journals (Sweden)

    Sousa Avinash

    2009-01-01

    Full Text Available Vocational and social issues affect rehabilitation and development of patients with cleft lip and cleft palate. However, psychological problems like lowered self esteem and difficulties in social interaction have also been noted in them. Not many pediatric reconstructive surgery teams have a psychiatrist on their panel. It is likely that psychological problems are higher in incidence than literature actually suggests. Hence it is very essential that such cases are identified by the surgical team to maximize positive outcome of surgery and rehabilitation. This study discusses psychological issues revolving around cleft lip and cleft palate along with lacunae in many psychological research studies.

  15. Prevalence of cleft lip and cleft palate in rural north-central guatemala.

    Science.gov (United States)

    Matute, Jorge; Lydick, Elaine A; Torres, Olga R; Owen, Karen K; Jacobsen, Kathryn H

    2015-05-01

    To estimate the number of new cases of cleft lip and cleft palate in the department (state) of Alta Verapaz, Guatemala, in 2012. Cross-sectional survey of midwives from communities identified through a two-stage cluster-sampling process. Midwives were asked how many babies they had delivered in the past year and how many of those newborns had various types of birth defects, as illustrated in pictures. Indigenous Mayan communities in rural north-central Guatemala. Midwives (n = 129) who had delivered babies in the previous year. Reports of babies born with cleft lip and cleft palate. A 1-year prevalence rate of 18.9 per 10,000 for cleft lip and 4.7 per 10,000 for cleft palate was estimated for Alta Verapaz. None of the cases of cleft lip also had cleft palate. The indigenous communities in north-central Guatemala might have a relatively high cleft lip prevalence rate compared with the global average.

  16. Endogenous GABA and Glutamate Finely Tune the Bursting of Olfactory Bulb External Tufted Cells

    Science.gov (United States)

    Hayar, Abdallah; Ennis, Matthew

    2008-01-01

    In rat olfactory bulb slices, external tufted (ET) cells spontaneously generate spike bursts. Although ET cell bursting is intrinsically generated, its strength and precise timing may be regulated by synaptic input. We tested this hypothesis by analyzing whether the burst properties are modulated by activation of ionotropic γ-aminobutyric acid (GABA) and glutamate receptors. Blocking GABAA receptors increased—whereas blocking ionotropic glutamate receptors decreased—the number of spikes/burst without changing the interburst frequency. The GABAA agonist (isoguvacine, 10 μM) completely inhibited bursting or reduced the number of spikes/burst, suggesting a shunting effect. These findings indicate that the properties of ET cell spontaneous bursting are differentially controlled by GABAergic and glutamatergic fast synaptic transmission. We suggest that ET cell excitatory and inhibitory inputs may be encoded as a change in the pattern of spike bursting in ET cells, which together with mitral/tufted cells constitute the output circuit of the olfactory bulb. PMID:17567771

  17. Distribution of vesicular glutamate transporters in the human brain

    Directory of Open Access Journals (Sweden)

    Erika eVigneault

    2015-03-01

    Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

  18. Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Shouqiang; Seven, Alpay B.; Wang, Jing; Skiniotis, Georgios; Özkan, Engin (UC); (Michigan)

    2016-12-01

    Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain. In contrast, we show that the interaction of cerebellin with isolated GluD2 ectodomain is low affinity, which is not simply an outcome of lost avidity when compared with binding with a tetrameric full-length receptor. Rather, high-affinity capture of cerebellin by post-synaptic terminals is likely controlled by long-distance regulation within this transsynaptic complex. Altogether, our results suggest unusual conformational flexibility within all components of the complex.

  19. Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate

    DEFF Research Database (Denmark)

    Leslie, Elizabeth J.; Carlson, Jenna C.; Shaffer, John R.

    2017-01-01

    Nonsyndromic orofacial clefts (OFCs) are a heterogeneous group of common craniofacial birth defects with complex etiologies that include genetic and environmental risk factors. OFCs are commonly categorized as cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which have h...

  20. NMDAR-mediated calcium transients elicited by glutamate co-release at developing inhibitory synapses

    Directory of Open Access Journals (Sweden)

    Abigail Kalmbach

    2010-07-01

    Full Text Available Before hearing onset, the topographic organization of the inhibitory sound localization pathway from the medial nucleus of the trapezoid body (MNTB to the lateral superior olive (LSO is refined by means of synaptic silencing and strengthening. During this refinement period MNTB-LSO synapses not only release GABA and glycine but also release glutamate. This co-released glutamate can elicit postsynaptic currents that are predominantly mediated by NMDA receptors (NMDARs. To gain a better understanding of how glutamate contributes to synaptic signaling at developing MNTB-LSO inhibitory synapse, we investigated to what degree and under what conditions NMDARs contribute to postsynaptic calcium responses. Our results demonstrate that MNTB-LSO synapses can elicit compartmentalized calcium responses along aspiny LSO dendrites. These responses are significantly attenuated by the NMDARs antagonist APV. APV, however, has no effect on somatically recorded electrical postsynaptic responses, indicating little, if any, contribution of NMDARs to spike generation. Small NMDAR-mediated calcium responses were also observed under physiological levels of extracellular magnesium concentrations indicating that MNTB-LSO synapses activate magnesium sensitive NMDAR on immature LSO dendrites. In Fura-2 AM loaded neurons, blocking GABAA and glycine receptors decreased NMDAR contribution to somatic calcium responses suggesting that GABA and glycine, perhaps by shunting backpropagating action potentials, decrease the level of NMDAR activation under strong stimulus conditions.

  1. Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus.

    Science.gov (United States)

    Besser, Limor; Chorin, Ehud; Sekler, Israel; Silverman, William F; Atkin, Stan; Russell, James T; Hershfinkel, Michal

    2009-03-04

    Zn(2+) is coreleased with glutamate from mossy fiber terminals and can influence synaptic function. Here, we demonstrate that synaptically released Zn(2+) activates a selective postsynaptic Zn(2+)-sensing receptor (ZnR) in the CA3 region of the hippocampus. ZnR activation induced intracellular release of Ca(2+), as well as phosphorylation of extracellular-regulated kinase and Ca(2+)/calmodulin kinase II. Blockade of synaptic transmission by tetrodotoxin or CdCl inhibited the ZnR-mediated Ca(2+) rises. The responses mediated by ZnR were largely attenuated by the extracellular Zn(2+) chelator, CaEDTA, and in slices from mice lacking vesicular Zn(2+), suggesting that synaptically released Zn(2+) triggers the metabotropic activity. Knockdown of the expression of the orphan G-protein-coupled receptor 39 (GPR39) attenuated ZnR activity in a neuronal cell line. Importantly, we observed widespread GPR39 labeling in CA3 neurons, suggesting a role for this receptor in mediating ZnR signaling in the hippocampus. Our results describe a unique role for synaptic Zn(2+) acting as the physiological ligand of a metabotropic receptor and provide a novel pathway by which synaptic Zn(2+) can regulate neuronal function.

  2. Abnormal glutamate release in aged BTBR mouse model of autism.

    Science.gov (United States)

    Wei, Hongen; Ding, Caiyun; Jin, Guorong; Yin, Haizhen; Liu, Jianrong; Hu, Fengyun

    2015-01-01

    Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Most of the available research on autism is focused on children and young adults and little is known about the pathological alternation of autism in older adults. In order to investigate the neurobiological alternation of autism in old age stage, we compared the morphology and synaptic function of excitatory synapses between the BTBR mice with low level sociability and B6 mice with high level sociability. The results revealed that the number of excitatory synapse colocalized with pre- and post-synaptic marker was not different between aged BTBR and B6 mice. The aged BTBR mice had a normal structure of dendritic spine and the expression of Shank3 protein in the brain as well as that in B6 mice. The baseline and KCl-evoked glutamate release from the cortical synaptoneurosome in aged BTBR mice was lower than that in aged B6 mice. Overall, the data indicate that there is a link between disturbances of the glutamate transmission and autism. These findings provide new evidences for the hypothesis of excitation/inhibition imbalance in autism. Further work is required to determine the cause of this putative abnormality.

  3. Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

    Science.gov (United States)

    Revett, Timothy J.; Baker, Glen B.; Jhamandas, Jack; Kar, Satyabrata

    2013-01-01

    Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid β peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid β and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid β production, but also amyloid β can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness. PMID:22894822

  4. Bright Promise for Your Child with Cleft Lip and Cleft Palate. Revised Edition.

    Science.gov (United States)

    McDonald, Eugene T.; Berlin, Asa J.

    Intended for parents of children with cleft lip and cleft palate, the booklet provides an overview of the condition. Addressed are the following topics (sample subtopics in parentheses): prenatal development and birth defects (facial development); possible causes of cleft lip/cleft palate (common misconceptions, genetic factors, environmental…

  5. Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats

    Science.gov (United States)

    Li, Xiao-Li; Yuan, Yong-Gui; Xu, Hua; Wu, Di; Gong, Wei-Gang; Geng, Lei-Yu; Wu, Fang-Fang; Tang, Hao; Xu, Lin

    2015-01-01

    Background: Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment. Methods: Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray’s Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats’ depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests. Results: The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats. Conclusion: These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats’ depressive behaviors, suggesting a therapeutic target for further exploration. PMID:25899067

  6. Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.

    Science.gov (United States)

    Shen, Yao; Tian, Yueyang; Shi, Xiaojie; Yang, Jianbo; Ouyang, Li; Gao, Jieqiong; Lu, Jianxin

    2014-08-01

    Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate-induced gliotoxicity. Exposure to 10-mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non-mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP-linked respiration of astrocytes was reduced. The glutamate-induced astrocyte damage can be mimicked by the non-metabolized substrate d-aspartate but reversed by the non-selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate-induced gliotoxicity in cortical astrocytes. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Dental anomalies inside the cleft region in individuals with nonsyndromic cleft lip with or without cleft palate.

    Science.gov (United States)

    Sá, Jamile; Araújo, Luana; Guimarães, Laís; Maranhão, Samário; Lopes, Gabriela; Medrado, Alena; Coletta, Ricardo; Reis, Silvia

    2016-01-01

    Individuals with nonsyndromic cleft lip with or without cleft palate (NSCL±P) present high frequency of dental anomalies, which may represent complicating factors for dental treatment. The aim of this study was to investigate the prevalence of dental anomalies inside cleft area in a group of Brazilians with NSCL±P. Retrospective analysis of 178 panoramic radiographs of patients aged from 12 to 45 years old and without history of tooth extraction or orthodontic treatment was performed. Association between cleft type and the prevalence of dental anomalies was assessed by chi-square test with a significance level set at p≤ 0.05. Dental anomalies were found in 88.2% (n=157) of the patients. Tooth agenesis (47.1%), giroversion (20%) and microdontia (15.5%) were the most common anomalies. Individuals with unilateral complete cleft lip and palate (CLP, pdental anomalies inside cleft region in NSCL±P patients, and further demonstrated that patients with unilateral complete CLP and bilateral incomplete CLP were frequently more affected by dental anomalies. Moreover, our results demonstrate that dental anomalies should be considered during dental treatment planning of individuals affected by NSCL±P.

  8. Characterization of the venom from the spider, Araneus gemma: search for a glutamate antagonist

    International Nuclear Information System (INIS)

    Early, S.L.

    1985-01-01

    Venom from three spiders, Argiope aurantia, Neoscona arabesca, and Araneus gemma have been shown to inhibit the binding of L-[ 3 H]glutamate to both GBP and synaptic membranes. The venom from Araneus gemma was shown to be the most potent of the three venoms in inhibiting the binding of L-[ 3 H]glutamate to GBP. Therefore, Araneus gemma venom was selected for further characterization. Venom from Araneus gemma appeared to contain two factors which inhibit the binding of L-[ 3 H]glutamate to GBP and at least one factor that inhibits L-glutamate-stimulated 35 SCN flux. Factor I is thought to be L-glutamic acid, based on: (1) its similar mobility to glutamic acid in thin-layer chromatography and amino acid analysis, (2) the presence of fingerprint molecular ion peaks for glutamate in the mass spectrum for the methanol:water (17:1) extract and for the fraction from the HPLC-purification of the crude venom, and (3) its L-glutamate-like interaction with the sodium-dependent uptake system. Factor II appears to be a polypeptide, possibly 21 amino acids in length, and does not appear to contain any free amino groups or tryptophan. While the venom does not appear to contain any indoleamines, three catecholamines (epinephrine, epinine, dopamine) and one catecholamine metabolite (DOPAC) were detected

  9. FOXE1 Association with both Isolated Cleft Lip with or without Cleft Palate; and Isolated Cleft Palate

    DEFF Research Database (Denmark)

    Moreno, Lina M; Mansilla, Maria Adela; Bullard, Steve A

    2009-01-01

    Nonsyndromic orofacial clefts are a common complex birth defect caused by genetic and environmental factors and/or their interactions. A previous genome-wide linkage scan discovered a novel locus for cleft lip with or without cleft palate (CL/P) at 9q22-q33. To identify the etiologic gene, we......) and rs4460498 (p=6.51E-12) were located inside a 70Kb high LD block containing FOXE1. Association signals for Caucasians and Asians clustered 5' and 3' of FOXE1, respectively. Isolated cleft palate (CP) was also associated indicating that FOXE1 plays a role in two phenotypes thought to be genetically...

  10. Endophilin A1 Promotes Actin Polymerization in Dendritic Spines Required for Synaptic Potentiation

    Directory of Open Access Journals (Sweden)

    Yanrui Yang

    2018-05-01

    Full Text Available Endophilin A1 is a member of the N-BAR domain-containing endophilin A protein family that is involved in membrane dynamics and trafficking. At the presynaptic terminal, endophilin As participate in synaptic vesicle recycling and autophagosome formation. By gene knockout studies, here we report that postsynaptic endophilin A1 functions in synaptic plasticity. Ablation of endophilin A1 in the hippocampal CA1 region of mature mouse brain impairs long-term spatial and contextual fear memory. Its loss in CA1 neurons postsynaptic of the Schaffer collateral pathway causes impairment in their AMPA-type glutamate receptor-mediated synaptic transmission and long-term potentiation. In KO neurons, defects in the structural and functional plasticity of dendritic spines can be rescued by overexpression of endophilin A1 but not A2 or A3. Further, endophilin A1 promotes actin polymerization in dendritic spines during synaptic potentiation. These findings reveal a physiological role of endophilin A1 distinct from that of other endophilin As at the postsynaptic site.

  11. Cleft Palate; A Multidiscipline Approach.

    Science.gov (United States)

    Stark, Richard B., Ed.

    Nineteen articles present a multidisciplinary approach to the management of facial clefts. The following subjects are discussed: the history of cleft lip and cleft palate surgery; cogenital defects; classification; the operation of a cleft palate clinic; physical examination of newborns with cleft lip and/or palate; nursing care; anesthesia;…

  12. Free amino acids in synaptic vesicles isolated from the cerebellum and cerebral hemispheres of control and neonatally X-irradiated rats

    International Nuclear Information System (INIS)

    Valcana, T.; Hudson, D.B.; Timiras, P.S.

    1984-01-01

    X-irradiation of the rat brain (1000R, at two days of age), suppresses the normal age-related increase in the weight of the cerebellum and cerebral hemispheres and influences amino acid levels. The decrease in glutamic acid concentration, particularly in the cerebellum, supports the previously advanced proposition that this amino acid may be associated with or may be the transmitter of, the rat cerebellar granule cells. Subfractionation of the cerebellar tissue reveals that the decrease in the glutamic acid level consequent to the loss of granule cells, is reflected in the cytoplasmic fraction but not in the synaptic vesicle subfraction, where glutamic acid was increased. The reduced weight gain in the cerebral hemispheres after irradiation, is accompanied by a significant decrease of aspartate in the cytoplasmic fraction, changes which suggest that a specific cell type, with aspartic acid as its neurotransmitter (possibly in the hippocampus), may also be radiosensitive in the early postnatal period. In contrast, in the synaptic vesicle fraction from cerebral hemispheres, all free amino acids, with the exception of glutamine, increased significantly. Overall, the changes in free amino acid concentration induced by X-irradiation in the cytoplasmic fraction in both brain regions studied are opposite to those found in the synaptic vesicle fraction and although they may indicate changes in specific cell populations, as proposed above, they could also reflect changes in cellular compartmentalization and metabolism or changes in the relative axonal arborization of the affected regions

  13. Recent advances in understanding synaptic abnormalities in Rett syndrome [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael Johnston

    2015-12-01

    Full Text Available Rett syndrome is an extremely disabling X-linked nervous system disorder that mainly affects girls in early childhood and causes autism-like behavior, severe intellectual disability, seizures, sleep disturbances, autonomic instability, and other disorders due to mutations in the MeCP2 (methyl CpG-binding protein 2 transcription factor. The disorder targets synapses and synaptic plasticity and has been shown to disrupt the balance between glutamate excitatory synapses and GABAergic inhibitory synapses. In fact, it can be argued that Rett syndrome is primarily a disorder of synaptic plasticity and that agents that can correct this imbalance may have beneficial effects on brain development. This review briefly summarizes the link between disrupted synaptic plasticity mechanisms and Rett syndrome and early clinical trials that aim to target these abnormalities to improve the outcome for these severely disabled children.

  14. Influence of lip closure on alveolar cleft width in patients with cleft lip and palate

    Directory of Open Access Journals (Sweden)

    Schmelzle Rainer

    2011-01-01

    Full Text Available Abstract Background The influence of surgery on growth and stability after treatment in patients with cleft lip and palate are topics still under discussion. The aim of the present study was to investigate the influence of early lip closure on the width of the alveolar cleft using dental casts. Methods A total of 44 clefts were investigated using plaster casts, 30 unilateral and 7 bilateral clefts. All infants received a passive molding plate a few days after birth. The age at the time of closure of the lip was 2.1 month in average (range 1-6 months. Plaster casts were obtained at the following stages: shortly after birth, prior to lip closure, prior to soft palate closure. We determined the width of the alveolar cleft before lip closure and prior to soft palate closure measuring the alveolar cleft width from the most lateral point of the premaxilla/anterior segment to the most medial point of the smaller segment. Results After lip closure 15 clefts presented with a width of 0 mm, meaning that the mucosa of the segments was almost touching one another. 19 clefts showed a width of up to 2 mm and 10 clefts were still over 2 mm wide. This means a reduction of 0% in 5 clefts, of 1-50% in 6 clefts, of 51-99% in 19 clefts, and of 100% in 14 clefts. Conclusions Early lip closure reduces alveolar cleft width. In most cases our aim of a remaining cleft width of 2 mm or less can be achieved. These are promising conditions for primary alveolar bone grafting to restore the dental bony arch.

  15. Prevalence of dental anomalies in children with cleft lip and unilateral and bilateral cleft lip and palate.

    Science.gov (United States)

    Rullo, R; Festa, V M; Rullo, R; Addabbo, F; Chiodini, P; Vitale, M; Perillo, L

    2015-09-01

    To examine the prevalence of different types of dental anomalies in children with nonsyndromic cleft lip, unilateral cleft lip-palate, and bilateral cleft lip-palate. A sample of 90 patients (aged 4-20 years) affected by isolated cleft lip, unilateral and bilateral cleft lip and palate was examined. Cleft patients were classified into one of three groups according to cleft type: (1) Unilateral Cleft Lip-Palate, (2) Bilateral Cleft Lip-Palate, and (3) Cleft Lip. Intraoral exams, panoramic radiographs and dental casts, were used to analyse the prevalence of the various dental anomalies included in this study. There were no statistically significant differences between patients with cleft lip, unilateral cleft lip and palate and bilateral cleft lip and palate. The congenital absence of the cleft-side lateral incisor was observed in 40% of the sample, and a total of 30% patients showed supernumerary teeth at the incisors region. Second premolar agenesis was found in 4.4% of patients, whereas in 18.9% of the sample there was an ectopic dental eruption. Lateral or central incisors rotation was noted in 31.1% of the sample, while shape anomaly, lateral incisor microdontia, and enamel hypoplasia were detected respectively in 25.6%, 5.6% and 18.9% of cleft patients. High prevalence of different dental anomalies in children with cleft lip and unilateral and bilateral cleft lip and palate has been confirmed. This study, in particular, shows the presence of ectopic and rotated teeth in the cleft area.

  16. Skull thickness in patients with clefts

    DEFF Research Database (Denmark)

    Arntsen, T; Kjaer, I; Sonnesen, L

    2010-01-01

    The purpose was to analyze skull thickness in incomplete cleft lip (CL), cleft palate (CP), and combined cleft lip and palate (UCLP).......The purpose was to analyze skull thickness in incomplete cleft lip (CL), cleft palate (CP), and combined cleft lip and palate (UCLP)....

  17. Dimensions of the cleft nasal airway in adults: a comparison with subjects without cleft.

    Science.gov (United States)

    Hairfield, W M; Warren, D W

    1989-01-01

    The prevalence of mouthbreathing among individuals with cleft lip and palate is significantly higher than in the normal population. This has been attributed to nasal deformities that tend to reduce nasal airway size. The purpose of the present study was to determine how a heterogeneous adult group with cleft lip and palate differs in terms of nasal airway cross-sectional area from an adult group without cleft during the inspiratory and expiratory phases of breathing. The pressure-flow technique was used to estimate nasal airway size in 15 adults without cleft (15 years or older) and 37 adults with cleft lip, cleft palate, or both. Mean areas and standard deviations for subjects without cleft were 0.63 cm2 +/- 0.17 during inspiration and 0.56 cm2 +/- 0.14 during expiration. This difference is statistically significant (p less than 0.01). Mean areas and standard deviations for all subjects with cleft were 0.37 cm2 +/- 0.18 during inspiration and 0.40 cm2 +/- 0.20 during expiration. This difference is not statistically significant (p greater than 0.15). Twenty-two of the subjects with cleft had nasal areas considered to be impaired (below 0.40 cm2) as compared with only three of the subjects without cleft. A two factor analysis of variance (ANOVA) demonstrated that area changes during respiration are different for subjects with and without cleft (p less than 0.005), and that cleft nasal areas are smaller than noncleft areas for both phases of breathing (p less than 0.001). Inspiratory-expiratory differences between subjects with and without cleft are probably the result of developmental defects, reparative surgery or both.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The "Double" Tessier 7 Cleft: An Unusual Presentation of a Transverse Facial Cleft.

    Science.gov (United States)

    Raveendran, Janani A; Chao, Jerry W; Rogers, Gary F; Boyajian, Michael J

    2018-07-01

    Congenital macrostomia, or Tessier number 7 cleft, is a rare craniofacial anomaly. We present a unique patient with bilateral macrostomia that consisted of a "double" transverse cleft on the left side and a single transverse cleft on the right side. A staged reconstructive approach was used to repair the "double" left-sided clefts. This staged technique produced a satisfactory aesthetic and functional outcome.

  19. Estradiol induces dendritic spines by enhancing glutamate release independent of transcription: A mechanism for organizational sex differences

    Science.gov (United States)

    Schwarz, Jaclyn M.; Liang, Shu-Ling; Thompson, Scott M.; McCarthy, Margaret M.

    2008-01-01

    SUMMARY The naturally occurring sex difference in dendritic spine number on hypothalamic neurons offers a unique opportunity to investigate mechanisms establishing synaptic patterning during perinatal sensitive periods. A major advantage of the model is the ability to treat neonatal females with estradiol to permanently induce the male phenotype. During the development of other systems, exuberant innervation is followed by activity-dependent pruning necessary for elimination of spurious synapses. In contrast, we demonstrate that estradiol-induced organization in the hypothalamus involves the induction of new synapses on dendritic spines. Activation of estrogen receptors by estradiol triggers a non-genomic activation of PI3 kinase that results in enhanced glutamate release from presynaptic neurons. Subsequent activation of ionotropic glutamate receptors activates MAP kinases inducing dendritic spine formation. These results reveal a trans-neuronal mechanism by which estradiol acts during a sensitive period to establish a profound and lasting sex difference in hypothalamic synaptic patterning. PMID:18498739

  20. A targeted glycan-related gene screen reveals heparan sulfate proteoglycan sulfation regulates WNT and BMP trans-synaptic signaling.

    Directory of Open Access Journals (Sweden)

    Neil Dani

    Full Text Available A Drosophila transgenic RNAi screen targeting the glycan genome, including all N/O/GAG-glycan biosynthesis/modification enzymes and glycan-binding lectins, was conducted to discover novel glycan functions in synaptogenesis. As proof-of-product, we characterized functionally paired heparan sulfate (HS 6-O-sulfotransferase (hs6st and sulfatase (sulf1, which bidirectionally control HS proteoglycan (HSPG sulfation. RNAi knockdown of hs6st and sulf1 causes opposite effects on functional synapse development, with decreased (hs6st and increased (sulf1 neurotransmission strength confirmed in null mutants. HSPG co-receptors for WNT and BMP intercellular signaling, Dally-like Protein and Syndecan, are differentially misregulated in the synaptomatrix of these mutants. Consistently, hs6st and sulf1 nulls differentially elevate both WNT (Wingless; Wg and BMP (Glass Bottom Boat; Gbb ligand abundance in the synaptomatrix. Anterograde Wg signaling via Wg receptor dFrizzled2 C-terminus nuclear import and retrograde Gbb signaling via synaptic MAD phosphorylation and nuclear import are differentially activated in hs6st and sulf1 mutants. Consequently, transcriptional control of presynaptic glutamate release machinery and postsynaptic glutamate receptors is bidirectionally altered in hs6st and sulf1 mutants, explaining the bidirectional change in synaptic functional strength. Genetic correction of the altered WNT/BMP signaling restores normal synaptic development in both mutant conditions, proving that altered trans-synaptic signaling causes functional differentiation defects.

  1. Exogenous hydrogen sulfide eliminates spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress via promoting glutamate uptake.

    Science.gov (United States)

    He, Jin; Guo, Ruixian; Qiu, Pengxin; Su, Xingwen; Yan, Guangmei; Feng, Jianqiang

    2017-05-14

    Acute stress impairs the hippocampus-dependent spatial memory retrieval, and its synaptic mechanisms are associated with hippocampal CA1 long-term depression (LTD) enhancement in the adult rats. Endogenous hydrogen sulfide (H 2 S) is recognized as a novel gasotransmitter and has the neural protective roles. However, very little attention has been paid to understanding the effects of H 2 S on spatial memory retrieval impairment. We observed the protective effects of NaHS (a donor of H 2 S) against spatial memory retrieval impairment caused by acute stress and its synaptic mechanisms. Our results showed that NaHS abolished spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress, but not by glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylic (tPDC), indicating that the activation of glutamate transporters is necessary for exogenous H 2 S to exert its roles. Moreover, NaHS restored the decreased glutamate uptake in the hippocampal CA1 synaptosomal fraction caused by acute stress. Dithiothreitol (DTT, a disulfide reducing agent) abolished a decrease in the glutamate uptake caused by acute stress, and NaHS eradicated the decreased glutamate uptake caused by 5,5'-dithio-bis(2-nitrobenzoic)acid (DTNB, a thiol oxidizing agent), collectively, revealing that exogenous H 2 S increases glutamate uptake by reducing disulfide bonds of the glutamate transporters. Additionally, NaHS inhibited the increased expression level of phosphorylated c-Jun-N-terminal kinase (JNK) in the hippocampal CA1 region caused by acute stress. The JNK inhibitor SP600125 eliminated spatial memory retrieval impairment, hippocampal CA1 LTD enhancement and the decreased glutamate uptake caused by acute stress, indicating that exogenous H 2 S exerts these roles by inhibiting the activation of JNK signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Cleft palate with/without cleft lip in French children: radiographic evaluation of prevalence, location and coexistence of dental anomalies inside and outside cleft region.

    Science.gov (United States)

    Mangione, Francesca; Nguyen, Laure; Foumou, Nathalie; Bocquet, Emmanuelle; Dursun, Elisabeth

    2018-03-01

    Prevalence of dental anomalies in cleft patients is higher than that in general population. The objectives of this study were to assess the prevalence of dental anomalies and their coexistence in French children with cleft and, then, to investigate the relation between the dental anomalies and the cleft type. Seventy-four non-syndromic cleft patients (6-16 years old) from Lille Regional University and Mondor-Chenevier Hospitals (France) were included. Clefts were classified as right/left unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP) and cleft palate (CP). Dental anomalies were investigated on panoramic radiographs and categorized as agenesis, supernumerary teeth, incisor rotations, impacted canines and shape anomalies. Prevalence and gender distribution of dental anomalies, mean number of affected teeth per patient, agenesis occurrence and location, and coexistence of dental anomalies were analysed by cleft type. 96.0% of patients presented at least one dental anomaly (agenesis 83.8%, incisor rotations 25.7%, shape anomalies 21.6%, impacted canines 18.9%, supernumerary teeth 8.1%). BCLP patients had a higher number of affected teeth, and left UCLP patients had a higher one compared to right UCLP patients. Distribution of inside (45.3%) and outside (54.7%) cleft region agenesis was similar. Adjacent (31.8%) and not adjacent (33.3%) combined dental anomalies were often encountered. Dental anomalies were localized inside as well as outside cleft region and were often associated with each other. BCLP patients were more affected. Early radiographic evaluation allows a comprehensive diagnosis of inside and outside cleft region anomalies, required for the multidisciplinary dental treatment.

  3. Feeding interventions for growth and development in infants with cleft lip, cleft palate or cleft lip and palate.

    Science.gov (United States)

    Bessell, Alyson; Hooper, Lee; Shaw, William C; Reilly, Sheena; Reid, Julie; Glenny, Anne-Marie

    2011-02-16

    Cleft lip and cleft palate are common birth defects, affecting about one baby of every 700 born. Feeding these babies is an immediate concern and there is evidence of delay in growth of children with a cleft as compared to those without clefting. In an effort to combat reduced weight for height, a variety of advice and devices are recommended to aid feeding of babies with clefts. This review aims to assess the effects of these feeding interventions in babies with cleft lip and/or palate on growth, development and parental satisfaction. The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 27 October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE via OVID (1950 to 27 October 2010), EMBASE via OVID (1980 to 27 October 2010), PsycINFO via OVID (1950 to 27 October 2010) and CINAHL via EBSCO (1980 to 27 October 2010). Attempts were made to identify both unpublished and ongoing studies. There was no restriction with regard to language of publication. Studies were included if they were randomised controlled trials (RCTs) of feeding interventions for babies born with cleft lip, cleft palate or cleft lip and palate up to the age of 6 months (from term). Studies were assessed for relevance independently and in duplicate. All studies meeting the inclusion criteria were data extracted and assessed for validity independently by each member of the review team. Authors were contacted for clarification or missing information whenever possible. Five RCTs with a total of 292 babies, were included in the review. Comparisons made within the RCTs were squeezable versus rigid feeding bottles (two studies), breastfeeding versus spoon-feeding (one study) and maxillary plate versus no plate (two studies). No statistically significant differences were shown for any of the primary outcomes when comparing bottle types, although squeezable bottles were less likely to require

  4. Cleft lip and palate repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002979.htm Cleft lip and palate repair To use the sharing features on this ... Cheiloplasty; Cleft rhinoplasty; Palatoplasty; Tip rhinoplasty Patient Instructions Cleft lip and palate repair - discharge Images Cleft lip repair - series References ...

  5. The Primary Care Pediatrician and the Care of Children With Cleft Lip and/or Cleft Palate.

    Science.gov (United States)

    Lewis, Charlotte W; Jacob, Lisa S; Lehmann, Christoph U

    2017-05-01

    Orofacial clefts, specifically cleft lip and/or cleft palate (CL/P), are among the most common congenital anomalies. CL/P vary in their location and severity and comprise 3 overarching groups: cleft lip (CL), cleft lip with cleft palate (CLP), and cleft palate alone (CP). CL/P may be associated with one of many syndromes that could further complicate a child's needs. Care of patients with CL/P spans prenatal diagnosis into adulthood. The appropriate timing and order of specific cleft-related care are important factors for optimizing outcomes; however, care should be individualized to meet the specific needs of each patient and family. Children with CL/P should receive their specialty cleft-related care from a multidisciplinary cleft or craniofacial team with sufficient patient and surgical volume to promote successful outcomes. The primary care pediatrician at the child's medical home has an essential role in making a timely diagnosis and referral; providing ongoing health care maintenance, anticipatory guidance, and acute care; and functioning as an advocate for the patient and a liaison between the family and the craniofacial/cleft team. This document provides background on CL/P and multidisciplinary team care, information about typical timing and order of cleft-related care, and recommendations for cleft/craniofacial teams and primary care pediatricians in the care of children with CL/P. Copyright © 2017 by the American Academy of Pediatrics.

  6. Long lasting protein synthesis- and activity-dependent spine shrinkage and elimination after synaptic depression.

    Directory of Open Access Journals (Sweden)

    Yazmín Ramiro-Cortés

    Full Text Available Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD mediated by metabotropic glutamate receptors (mGluRs through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation.

  7. Evidence-Based Medicine: Cleft Palate.

    Science.gov (United States)

    Woo, Albert S

    2017-01-01

    After studying this article, the participant should be able to: 1. Describe the incidence of cleft palate and risk factors associated with development of an orofacial cleft. 2. Understand differences among several techniques to repair clefts of both the hard and soft palates. 3. Discuss risk factors for development of postoperative fistulas, velopharyngeal insufficiency, and facial growth problems. 4. Establish a treatment plan for individualized care of a cleft palate patient. Orofacial clefts are the most common congenital malformations of the head and neck region, and approximately three-quarters of these patients have some form of cleft palate deformity. Cleft palate repair is generally performed in children between 6 and 12 months of age. The goals of palate repair are to minimize the occurrence of fistulas, establish a normal velopharyngeal mechanism, and optimize facial growth. This Maintenance of Certification review discusses the incidence and epidemiology associated with cleft palate deformity and specifics associated with patient care, including analgesia, surgical repair techniques, and complications associated with repair of the cleft palate.

  8. Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions

    Directory of Open Access Journals (Sweden)

    Carmine Tomasetti

    2017-01-01

    Full Text Available Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of “synapse-based” psychiatric therapeutic strategies.

  9. Prevalence of orofacial clefts and risks for nonsyndromic cleft lip with or without cleft palate in newborns at a university hospital from West Mexico.

    Science.gov (United States)

    Corona-Rivera, Jorge Román; Bobadilla-Morales, Lucina; Corona-Rivera, Alfredo; Peña-Padilla, Christian; Olvera-Molina, Sandra; Orozco-Martín, Miriam A; García-Cruz, Diana; Ríos-Flores, Izabel M; Gómez-Rodríguez, Brian Gabriel; Rivas-Soto, Gemma; Pérez-Molina, J Jesús

    2018-02-19

    We determined the overall prevalence of typical orofacial clefts and the potential risks for nonsyndromic cleft lip with or without cleft palate in a university hospital from West México. For the prevalence, 227 liveborn infants with typical orofacial clefts were included from a total of 81,193 births occurred during the period 2009-2016 at the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Guadalajara, Jalisco, Mexico). To evaluate potential risks, a case-control study was conducted among 420 newborns, including only those 105 patients with nonsyndromic cleft lip with or without cleft palate (cases), and 315 infants without birth defects (controls). Data were analyzed using multivariable logistic regression analysis expressed as adjusted odds ratio with 95% confidence intervals . The overall prevalence for typical orofacial clefts was 28 per 10,000 (95% confidence interval: 24.3-31.6), or 1 per 358 live births. The mean values for the prepregnancy weight, antepartum weight, and pre-pregnancy body mass index were statistically higher among the mothers of cases. Infants with nonsyndromic cleft lip with or without cleft palate had a significantly higher risk for previous history of any type of congenital anomaly (adjusted odds ratio: 2.7; 95% confidence interval: 1.4-5.1), history of a relative with cleft lip with or without cleft palate (adjusted odds ratio: 19.6; 95% confidence interval: 8.2-47.1), and first-trimester exposures to progestogens (adjusted odds ratio: 6.8; 95% CI 1.8-25.3), hyperthermia (adjusted odds ratio: 3.4; 95% confidence interval: 1.1-10.6), and common cold (adjusted odds ratio: 3.6; 95% confidence interval: 1.1-11.9). These risks could have contributed to explain the high prevalence of orofacial clefts in our region of Mexico, emphasizing that except for history of relatives with cleft lip with or without cleft palate, most are susceptible of modification. © 2018 Japanese Teratology Society.

  10. Cleft sidedness and congenitally missing teeth in patients with cleft lip and palate patients

    Directory of Open Access Journals (Sweden)

    Abdolreza Jamilian

    2016-05-01

    Full Text Available Abstract Background The aim of this study was to investigate the prevalence of cleft sidedness, and the number of congenitally missing teeth in regard to cleft type and gender. Methods The charts, models, radiographs, and intraoral photographs of 201 cleft patients including 131 males with the mean age of 12.3 ± 4 years and 70 females with the mean age of 12.6 ± 3.9 years were used for the study. T test, Chi-square, and binomial tests were used for assessment of the data. Results and conclusions One hundred forty-eight of the subjects suffered from cleft lip and palate followed by 41 subjects who suffered from cleft lip and alveolus. Chi-square test did not show any significant difference between the genders. Binomial test showed that left-sided cleft was more predominant in unilateral cleft lip and palate patients (P < 0.001. This study also showed that the upper lateral incisors were the most commonly missing teeth in the cleft area.

  11. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

    Science.gov (United States)

    Fuente-Martín, Esther; García-Cáceres, Cristina; Granado, Miriam; de Ceballos, María L.; Sánchez-Garrido, Miguel Ángel; Sarman, Beatrix; Liu, Zhong-Wu; Dietrich, Marcelo O.; Tena-Sempere, Manuel; Argente-Arizón, Pilar; Díaz, Francisca; Argente, Jesús; Horvath, Tamas L.; Chowen, Julie A.

    2012-01-01

    Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity. PMID:23064363

  12. Synaptic glutamate release by postnatal rat serotonergic neurons in microculture.

    Science.gov (United States)

    Johnson, M D

    1994-02-01

    Serotonergic neurons are thought to play a role in depression and obsessive compulsive disorder. However, their functional transmitter repertoire is incompletely known. To investigate this repertoire, intracellular recordings were obtained from 132 cytochemically identified rat mesopontine serotonergic neurons that had re-established synapses in microcultures. Approximately 60% of the neurons evoked excitatory glutamatergic potentials in themselves or in target neurons. Glutamatergic transmission was frequently observed in microcultures containing a solitary serotonergic neuron. Evidence for co-release of serotonin and glutamate from single raphe neurons was also obtained. However, evidence for gamma-aminobutyric acid release by serotonergic neurons was observed in only two cases. These findings indicate that many cultured serotonergic neurons form glutamatergic synapses and may explain several observations in slices and in vivo.

  13. Short mandible - a possible risk factor for cleft palate with/without a cleft lip

    DEFF Research Database (Denmark)

    Hermann, Nuno Vibe; Darvann, Tron Andre; Ersbøll, Bjarne Kjær

    2014-01-01

    Structured Abstract Objectives To estimate the influence of a short mandible on the risk of developing a cleft palate with/without a cleft lip (CP). Setting and sample population The retrospective sample consisted of 115 2-month-old Danish infants with CP, and 70 control infants with unilateral...... the risk of having a cleft palate. Results The mean mandibular length in the group with CP was about 4mm shorter than in the control group. Odds ratio (OR) was calculated to be 0.58 (95% confidence interval 0.48-0.68), implying that an individual's risk of cleft palate with/without a cleft lip increases...... about 50% per mm decrease in mandibular length. Conclusions A special facial type including a short mandible is a possible risk factor for cleft palate, and it was found that the risk of cleft palate increases 58% per mm decreases in mandibular length....

  14. Cleft Lip and Cleft Palate Surgery: Malpractice Litigation Outcomes.

    Science.gov (United States)

    Justin, Grant A; Brietzke, Scott E

    2017-01-01

      This study examined malpractice claims related to cleft lip and cleft palate surgery to identify common allegations and injuries and reviewed financial outcomes.   The WestlawNext legal database was analyzed for all malpractice lawsuits and settlements related to the surgical repair of cleft lip and palate.   Inclusion criteria included patients undergoing surgical repair of a primary cleft lip or palate or revision for complications of previous surgery. Data evaluated included patient demographics, type of operation performed, plaintiff allegation, nature of injury, and litigation outcomes.   A total of 36 cases were identified, with 12 unique cases from 1981 to 2006 meeting the inclusion criteria. Six cases (50%) were decided by a jury and six by settlement. Five cases involved complications related to the specific surgery, and the other seven were associated with any surgery and perioperative care of children and adults. Cleft palate repair (50%) was the most frequently litigated surgery. Postoperative negligent supervision was the most common allegation (42%) and resulted in a payout in each case (mean = $3,126,032). Death (42%) and brain injury (25%) were the most frequent injuries reported. Financial awards were made in nine cases (after adjusting for inflation, mean = $2,470,552, range = $0 to $7,704,585). The awards were significantly larger for brain injury than other outcomes ($4,675,395 versus $1,368,131 after adjusting for inflation, P = .0101).   Malpractice litigation regarding cleft lip and palate surgery is uncommon. However, significant financial awards involving perioperative brain injury have been reported.

  15. A study on the dental anomalities and site of cleft associated with cleft lip and/or palate

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Ahn, Hyung Kyu

    1985-01-01

    The purpose of this study is to investigate possible correlation between the dental anomalies and site of cleft in cleft lip and palate. In this study, 142 patients who had cleft lip and/or cleft palate were examined. The results are as follows. 1. The incidence of missing tooth was high in the permanent dentition as compared to the incidence in the deciduous dentition. 2. There was not much difference of incidence of supernumerary tooth between deciduous and permanent dentition in the group of patients who had cleft lip and jaw with or without cleft palate. 3. In the group of patients who had cleft lip and jaw with or without cleft palate, the frequency of incidence of cleft sides was higher in unilateral than bilateral cases. And, incidence of left sides was higher than right sides. 4. The type of cleft between central incisor and canine with missing lateral incisor was most frequent in permanent dentition and the type of cleft between central and lateral incisor was most frequent in deciduous dentition. 5. The type of cleft associated with tooth position in deciduous dentition was not almost the same in the succeeding permanent dentition.

  16. A study on the dental anomalities and site of cleft associated with cleft lip and/or palate

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Kyung; Ahn, Hyung Kyu [Department of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1985-11-15

    The purpose of this study is to investigate possible correlation between the dental anomalies and site of cleft in cleft lip and palate. In this study, 142 patients who had cleft lip and/or cleft palate were examined. The results are as follows. 1. The incidence of missing tooth was high in the permanent dentition as compared to the incidence in the deciduous dentition. 2. There was not much difference of incidence of supernumerary tooth between deciduous and permanent dentition in the group of patients who had cleft lip and jaw with or without cleft palate. 3. In the group of patients who had cleft lip and jaw with or without cleft palate, the frequency of incidence of cleft sides was higher in unilateral than bilateral cases. And, incidence of left sides was higher than right sides. 4. The type of cleft between central incisor and canine with missing lateral incisor was most frequent in permanent dentition and the type of cleft between central and lateral incisor was most frequent in deciduous dentition. 5. The type of cleft associated with tooth position in deciduous dentition was not almost the same in the succeeding permanent dentition.

  17. Astrocytes and Glutamate Homoeostasis in Alzheimer's Disease: A Decrease in Glutamine Synthetase, But Not in Glutamate Transporter-1, in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Magdalena Kulijewicz-Nawrot

    2013-09-01

    Full Text Available Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system. Being principal homoeostatic cells, astroglia are fundamental for various forms of neuropathology, including AD (Alzheimer's disease. AD is a progressive neurodegenerative disorder characterized by the loss of cognitive functions due to specific lesions in mnesic-associated regions, including the mPFC (medial prefrontal cortex. Here, we analyzed the expression of GS (glutamine synthetase and GLT-1 (glutamate transporter-1 in astrocytes in the mPFC during the progression of AD in a triple-transgenic mouse model (3xTg-AD. GS is an astrocyte-specific enzyme, responsible for the intracellular conversion of glutamate into glutamine, whereas the removal of glutamate from the extracellular space is accomplished mainly by astroglia-specific GLT-1. We found a significant decrease in the numerical density (Nv, cells/mm3 of GS-positive astrocytes from early to middle ages (1–9 months; at the age of 1 month by 17%, 6 months by 27% and 9 months by 27% when compared with control animals in parallel with a reduced expression of GS (determined by Western blots, which started at the age of 6 months and was sustained up to 12 months of age. We did not, however, find any changes in the expression of GLT-1, which implies an intact glutamate uptake mechanism. Our results indicate that the decrease in GS expression may underlie a gradual decline in the vital astrocyte-dependent glutamate–glutamine conversion pathway, which in turn may compromise glutamate homoeostasis, leading towards failures in synaptic connectivity with deficient cognition and memory.

  18. Branchial cleft anomalies: CT evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Seok, Eul Hye; Park, Chan Sup [College of Medicine, Inha University, Seongnam (Korea, Republic of)

    1994-04-15

    The purpose of this paper is to describe the CT findings of a variety of branchial cleft anomalies in the head and neck area. We reviewed the CT findings of 16 patients with neck lesion pathologically proved as branchial cleft anomalies. There were two first and 12 second branchial cleft cysts, one first and one second branchial cleft sinuses. Two cases of first branchial cleft cysts were manifested as thin-walled, cystic masses at auricular area. One first branchial cleft sinus was an external opening type and manifested as an ill-defined, enhancing solid lesion at posterior auricular area. All 12 cases of second branchial cleft cysts demonstrated a typical location, displacing the sternocleidomastoid muscle posteriorly, the carotid artery and internal jugular vein complex medially and the submandibular gland anteriorly. Eight cases of second branchial cleft cysts were seen as fluid-filled, round or ovoid-shaped cysts, and 3 cases of them were seen as irregular-shaped cysts. In one case, suppurative adenopathy with loss of soft tissue planes around the cyst was observed. One case of second branchial cleft sinus was manifested as a tubular-shaped, enhancing lesion at submental area and containing external opening site draining into the anterior border of the sternocleidomastoid muscle. We conclude that CT provides important diagnostic and therapeutic information in patients with a neck mass believed to be a branchial cleft anomaly, as it can differentiate various forms of the branchial anomalies by their characteristic location and shape.

  19. Branchial cleft anomalies: CT evaluation

    International Nuclear Information System (INIS)

    Seok, Eul Hye; Park, Chan Sup

    1994-01-01

    The purpose of this paper is to describe the CT findings of a variety of branchial cleft anomalies in the head and neck area. We reviewed the CT findings of 16 patients with neck lesion pathologically proved as branchial cleft anomalies. There were two first and 12 second branchial cleft cysts, one first and one second branchial cleft sinuses. Two cases of first branchial cleft cysts were manifested as thin-walled, cystic masses at auricular area. One first branchial cleft sinus was an external opening type and manifested as an ill-defined, enhancing solid lesion at posterior auricular area. All 12 cases of second branchial cleft cysts demonstrated a typical location, displacing the sternocleidomastoid muscle posteriorly, the carotid artery and internal jugular vein complex medially and the submandibular gland anteriorly. Eight cases of second branchial cleft cysts were seen as fluid-filled, round or ovoid-shaped cysts, and 3 cases of them were seen as irregular-shaped cysts. In one case, suppurative adenopathy with loss of soft tissue planes around the cyst was observed. One case of second branchial cleft sinus was manifested as a tubular-shaped, enhancing lesion at submental area and containing external opening site draining into the anterior border of the sternocleidomastoid muscle. We conclude that CT provides important diagnostic and therapeutic information in patients with a neck mass believed to be a branchial cleft anomaly, as it can differentiate various forms of the branchial anomalies by their characteristic location and shape

  20. Cleft Lip and Cleft Palate--What to Know and Who Can Help

    Science.gov (United States)

    Apel, Laura

    2008-01-01

    Craniofacial defects such as cleft lip and cleft palate are among the most common of all birth defects in the United States, with one in every 600 newborns affected. Cleft lip and/or palate can occur as an isolated condition or may be one component of an inherited disease or syndrome. Dealing with the condition is an extremely difficult and…

  1. Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

    Science.gov (United States)

    Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

    2015-01-01

    Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

  2. Patterns of orofacial clefting in the facial morphology of bats: a possible naturally occurring model of cleft palate.

    Science.gov (United States)

    Orr, David J A; Teeling, Emma C; Puechmaille, Sébastien J; Finarelli, John A

    2016-11-01

    A normal feature of the facial anatomy of many species of bat is the presence of bony discontinuities or clefts, which bear a remarkable similarity to orofacial clefts that occur in humans as a congenital pathology. These clefts occur in two forms: a midline cleft between the two premaxillae (analogous to the rare midline craniofacial clefts in humans) and bilateral paramedian clefts between the premaxilla and the maxillae (analogous to the typical cleft lip and palate in humans). Here, we describe the distribution of orofacial clefting across major bat clades, exploring the relationship of the different patterns of clefting to feeding mode, development of the vomeronasal organ, development of the nasolacrimal duct and mode of emission of the echolocation call in different bat groups. We also present the results of detailed radiographic and soft tissue dissections of representative examples of the two types of cleft. The midline cleft has arisen independently multiple times in bat phylogeny, whereas the paramedian cleft has arisen once and is a synapomorphy uniting the Rhinolophidae and Hipposideridae. In all cases examined, the bony cleft is filled in by a robust fibrous membrane, continuous with the periosteum of the margins of the cleft. In the paramedian clefts, this membrane splits to enclose the premaxilla but forms a loose fold laterally between the premaxilla and maxilla, allowing the premaxilla and nose-leaf to pivot dorsoventrally in the sagittal plane under the action of facial muscles attached to the nasal cartilages. It is possible that this is a specific adaptation for echolocation and/or aerial insectivory. Given the shared embryological location of orofacial clefts in bats and humans, it is likely that aspects of the developmental control networks that produce cleft lip and palate in humans may also be implicated in the formation of these clefts as a normal feature in some bats. A better understanding of craniofacial development in bats with and

  3. Fetal cleft lip with and without cleft palate: Comparison between MR imaging and US for prenatal diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Wang Guangbin, E-mail: wgb7932596@hotmail.com [Shandong Medical Imaging Research Institute, 324 Jingwu Road, Jinan, 250021 (China); Shan Ruiqin [Jinan Maternity and Child Care Hospital, Jinan (China); Zhao Lianxin; Zhu Xiangyu; Zhang Xinjuan [Shandong Medical Imaging Research Institute, 324 Jingwu Road, Jinan, 250021 (China)

    2011-09-15

    Objective: To describe the magnetic resonance (MR) imaging findings of fetal CL/CP and evaluate its diagnostic value. Methods and materials: Twelve fetuses with CL/CP diagnosed by transabdominal US underwent MR imaging within 2 days of US. Half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence on T2-weighted images was performed on sagittal, coronal, and axial planes anatomic to the fetuses during maternal breath holding. US and MR imaging findings were compared with final diagnoses obtained from post-natal physical examination or fetal autopsy. Results: Final diagnoses confirmed incomplete midline cleft lip (n = 1), unilateral cleft lip and palate (n = 7), bilateral cleft lip and palate (n = 1), midline cleft lip and palate (n = 3). US and MR imaging diagnosed all 12 fetuses with cleft lip and the laterality. 5 (45.5%) of 11 cleft palates were identified with US, 2 of 7 fetuses with unilateral cleft palate, 2 of 3 fetuses with midline cleft palate, and one fetus with bilateral cleft palate. On MR imaging, 10 (91%) of 11 cleft palates were correctly detected. One fetus with unilateral cleft palate was not detected. No false-positives occurred. Conclusion: MR imaging is valuable for diagnosis of fetal CL/CP. It can demonstrate additional findings and provide more information compared with US.

  4. Fetal cleft lip with and without cleft palate: Comparison between MR imaging and US for prenatal diagnosis

    International Nuclear Information System (INIS)

    Wang Guangbin; Shan Ruiqin; Zhao Lianxin; Zhu Xiangyu; Zhang Xinjuan

    2011-01-01

    Objective: To describe the magnetic resonance (MR) imaging findings of fetal CL/CP and evaluate its diagnostic value. Methods and materials: Twelve fetuses with CL/CP diagnosed by transabdominal US underwent MR imaging within 2 days of US. Half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence on T2-weighted images was performed on sagittal, coronal, and axial planes anatomic to the fetuses during maternal breath holding. US and MR imaging findings were compared with final diagnoses obtained from post-natal physical examination or fetal autopsy. Results: Final diagnoses confirmed incomplete midline cleft lip (n = 1), unilateral cleft lip and palate (n = 7), bilateral cleft lip and palate (n = 1), midline cleft lip and palate (n = 3). US and MR imaging diagnosed all 12 fetuses with cleft lip and the laterality. 5 (45.5%) of 11 cleft palates were identified with US, 2 of 7 fetuses with unilateral cleft palate, 2 of 3 fetuses with midline cleft palate, and one fetus with bilateral cleft palate. On MR imaging, 10 (91%) of 11 cleft palates were correctly detected. One fetus with unilateral cleft palate was not detected. No false-positives occurred. Conclusion: MR imaging is valuable for diagnosis of fetal CL/CP. It can demonstrate additional findings and provide more information compared with US.

  5. Schizencephaly/congenital cerebral clefts

    International Nuclear Information System (INIS)

    Friedman, H.; Naidich, T.P.

    1987-01-01

    Schizencephaly (from the Greek meaning ''split brain''), is a term developed in the 1940s to explain symmetric clefts in the brain seen at autopsy in children with histories of severe neurologic defects. Use of the term has been expanded to include a variety of cerebral clefts. A review of the experience at Children's Memorial Hospital as well as case materials made available to the authors are presented, including CT, MR imaging, and US findings. Theories of etiology and pathogenesis of these congenital clefts, associated anomalies, and the spectrum of appearance of these clefts are discussed

  6. Cleft Palate Foundation

    Science.gov (United States)

    ... craniofacial journeys. Read the press release here. American Cleft Palate-Craniofacial Association 1504 East Franklin Street, Suite 102 ... order bottles Order ACPA publications © Copyright 2017 American Cleft Palate-Craniofacial Association. Website by Mixer Creative Follow us ...

  7. Possible Contributions of a Novel Form of Synaptic Plasticity in "Aplysia" to Reward, Memory, and Their Dysfunctions in Mammalian Brain

    Science.gov (United States)

    Hawkins, Robert D.

    2013-01-01

    Recent studies in "Aplysia" have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in…

  8. Maternal Risk Factors Associated with Cleft Lip with or without Cleft Palate: A Review

    OpenAIRE

    Barrera, Catalina; Mezarobba, Naiara

    2016-01-01

    Disruptions in the development of the nasal and oral structures lead to cleft palate and cleft lip. There are many different factors that can affect this development such as genetic, mechanical traumas or teratogeny. The oral clefts are one of the most common birth defects worldwide affecting approximately 1 in 700 to 1000 children. The development of oral clefts is multifactorial and affect a significant portion of the population. The study results showed that smoking is the risk factor most...

  9. Preoperative Cleft Lip Measurements and Maxillary Growth in Patients With Unilateral Cleft Lip and Palate.

    Science.gov (United States)

    Antonarakis, Gregory S; Tompson, Bryan D; Fisher, David M

    2016-11-01

    Maxillary growth in patients with cleft lip and palate is highly variable. The authors' aim was to investigate associations between preoperative cleft lip measurements and maxillary growth determined cephalometrically in patients with complete unilateral cleft lip and palate (cUCLP). Retrospective cross-sectional study. Children with cUCLP. Preoperative cleft lip measurements were made at the time of primary cheiloplasty and available for each patient. Maxillary growth was evaluated on lateral cephalometric radiographs taken prior to any orthodontic treatment and alveolar bone grafting (8.5 ± 0.7 years). The presence of associations between preoperative cleft lip measurements and cephalometric measures of maxillary growth was determined using regression analyses. In the 58 patients included in the study, the cleft lateral lip element was deficient in height in 90% and in transverse width in 81% of patients. There was an inverse correlation between cleft lateral lip height and transverse width with a β coefficient of -0.382 (P = .003). Patients with a more deficient cleft lateral lip height displayed a shorter maxillary length (β coefficient = 0.336; P = .010), a less protruded maxilla (β coefficient = .334; P = .008), and a shorter anterior maxillary height (β coefficient = 0.306; P = .020) than those with a less deficient cleft lateral lip height. Patients with cUCLP present with varying degrees of lateral lip hypoplasia. Preoperative measures of lateral lip deficiency are related to later observed deficiencies of maxillary length, protrusion, and height.

  10. Increase of extracellular glutamate concentration increases its oxidation and diminishes glucose oxidation in isolated mouse hippocampus: reversible by TFB-TBOA.

    Science.gov (United States)

    Torres, Felipe Vasconcelos; Hansen, Fernanda; Locks-Coelho, Lucas Doridio

    2013-08-01

    Glutamate concentration at the synaptic level must be kept low in order to prevent excitotoxicity. Astrocytes play a key role in brain energetics, and also astrocytic glutamate transporters are responsible for the vast majority of glutamate uptake in CNS. Experiments with primary astrocytic cultures suggest that increased influx of glutamate cotransported with sodium at astrocytes favors its flux to the tricarboxylic acid cycle instead of the glutamate-glutamine cycle. Although metabolic coupling can be considered an emergent field of research with important recent discoveries, some basic aspects of glutamate metabolism still have not been characterized in brain tissue. Therefore, the aim of this study was to investigate whether the presence of extracellular glutamate is able to modulate the use of glutamate and glucose as energetic substrates. For this purpose, isolated hippocampi of mice were incubated with radiolabeled substrates, and CO2 radioactivity and extracellular lactate were measured. Our results point to a diminished oxidation of glucose with increasing extracellular glutamate concentration, glutamate presumably being the fuel, and might suggest that oxidation of glutamate could buffer excitotoxic conditions by high glutamate concentrations. In addition, these findings were reversed when glutamate uptake by astrocytes was impaired by the presence of (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA). Taken together, our findings argue against the lactate shuttle theory, because glutamate did not cause any detectable increase in extracellular lactate content (or, presumably, in glycolysis), because the glutamate is being used as fuel instead of going to glutamine and back to neurons. Copyright © 2013 Wiley Periodicals, Inc.

  11. Oral Clefts and Academic Performance in Adolescence

    DEFF Research Database (Denmark)

    Clausen, Nicola G; Pedersen, Dorthe A; Pedersen, Jacob K

    2017-01-01

    OBJECTIVE:   Early life exposure to anesthesia and surgery is suspected to associate with cognitive impairment later in life. We compared academic achievement among adolescents with cleft lip only (CL), cleft palate only (CP), and cleft lip and cleft palate (CLP) with a noncleft control group to ......:   Oral cleft type rather than number and timing of anesthesia and operations associate to poorer academic performance. Although a potential neurotoxic effect due to anesthetic agents is not reflected in the data, it cannot be completely excluded.......OBJECTIVE:   Early life exposure to anesthesia and surgery is suspected to associate with cognitive impairment later in life. We compared academic achievement among adolescents with cleft lip only (CL), cleft palate only (CP), and cleft lip and cleft palate (CLP) with a noncleft control group...

  12. Fetal genetic risk of isolated cleft lip only versus isolated cleft lip and palate: A subphenotype analysis using two population-based studies of orofacial clefts in scandinavia

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian

    2010-01-01

    BACKGROUND: Cleft lip only (CLO) and cleft lip and palate (CLP) are commonly regarded as variants of the same defect and are traditionally combined to form the single group of cleft lip with or without cleft palate (CL/P) prior to analysis. However, recent data have suggested that at least a subg...

  13. Psychological issues in cleft lip and cleft palate

    OpenAIRE

    Sousa Avinash; Devare Shibani; Ghanshani Jyoti

    2009-01-01

    Vocational and social issues affect rehabilitation and development of patients with cleft lip and cleft palate. However, psychological problems like lowered self esteem and difficulties in social interaction have also been noted in them. Not many pediatric reconstructive surgery teams have a psychiatrist on their panel. It is likely that psychological problems are higher in incidence than literature actually suggests. Hence it is very essential that such cases are identified by the surgical t...

  14. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals

    International Nuclear Information System (INIS)

    Lin, Tzu-Yu; Lu, Cheng-Wei; Wang, Chia-Chuan; Lu, Jyh-Feng; Wang, Su-Jane

    2012-01-01

    Hispidulin, a naturally occurring flavone, has been reported to have an antiepileptic profile. An excessive release of glutamate is considered to be related to neuropathology of epilepsy. We investigated whether hispidulin affected endogenous glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Hispidulin inhibited the release of glutamate evoked by the K + channel blocker 4-aminopyridine (4-AP). The effects of hispidulin on the evoked glutamate release were prevented by the chelation of extracellular Ca 2+ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate did not have any effect on hispidulin action. Hispidulin reduced the depolarization-induced increase in cytosolic free Ca 2+ concentration ([Ca 2+ ] C ), but did not alter 4-AP-mediated depolarization. Furthermore, the effect of hispidulin on evoked glutamate release was abolished by blocking the Ca v 2.2 (N-type) and Ca v 2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na + /Ca 2+ exchange. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of hispidulin on evoked glutamate release. Western blot analyses showed that hispidulin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK; this decrease was also blocked by the MEK inhibitor. Moreover, the inhibition of glutamate release by hispidulin was strongly attenuated in mice without synapsin I. These results show that hispidulin inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca 2+ entry and ERK/synapsin I signaling pathway. -- Highlights: ► Hispidulin inhibited glutamate release from rat cerebrocortical synaptosomes. ► This action did

  15. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tzu-Yu [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China); Department of Mechanical Engineering, Yuan Ze University, Taoyuan, 320, Taiwan (China); Lu, Cheng-Wei [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei, 22060, Taiwan (China); Wang, Chia-Chuan; Lu, Jyh-Feng [School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China); Wang, Su-Jane, E-mail: med0003@mail.fju.edu.tw [Graduate Institute of Basic Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China); School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei, 24205, Taiwan (China)

    2012-09-01

    Hispidulin, a naturally occurring flavone, has been reported to have an antiepileptic profile. An excessive release of glutamate is considered to be related to neuropathology of epilepsy. We investigated whether hispidulin affected endogenous glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Hispidulin inhibited the release of glutamate evoked by the K{sup +} channel blocker 4-aminopyridine (4-AP). The effects of hispidulin on the evoked glutamate release were prevented by the chelation of extracellular Ca{sup 2+} ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate did not have any effect on hispidulin action. Hispidulin reduced the depolarization-induced increase in cytosolic free Ca{sup 2+} concentration ([Ca{sup 2+}]{sub C}), but did not alter 4-AP-mediated depolarization. Furthermore, the effect of hispidulin on evoked glutamate release was abolished by blocking the Ca{sub v}2.2 (N-type) and Ca{sub v}2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na{sup +}/Ca{sup 2+} exchange. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of hispidulin on evoked glutamate release. Western blot analyses showed that hispidulin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK; this decrease was also blocked by the MEK inhibitor. Moreover, the inhibition of glutamate release by hispidulin was strongly attenuated in mice without synapsin I. These results show that hispidulin inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca{sup 2+} entry and ERK/synapsin I signaling pathway. -- Highlights: ► Hispidulin inhibited glutamate release from rat

  16. Transcriptomic responses in mouse brain exposed to chronic excess of the neurotransmitter glutamate

    Directory of Open Access Journals (Sweden)

    Pal Ranu

    2010-06-01

    Full Text Available Abstract Background Increases during aging in extracellular levels of glutamate (Glu, the major excitatory neurotransmitter in the brain, may be linked to chronic neurodegenerative diseases. Little is known about the molecular responses of neurons to chronic, moderate increases in Glu levels. Genome-wide gene expression in brain hippocampus was examined in a unique transgenic (Tg mouse model that exhibits moderate Glu hyperactivity throughout the lifespan, the neuronal Glutamate dehydrogenase (Glud1 mouse, and littermate 9 month-old wild type mice. Results Integrated bioinformatic analyses on transcriptomic data were used to identify bio-functions, pathways and gene networks underlying neuronal responses to increased Glu synaptic release. Bio-functions and pathways up-regulated in Tg mice were those associated with oxidative stress, cell injury, inflammation, nervous system development, neuronal growth, and synaptic transmission. Increased gene expression in these functions and pathways indicated apparent compensatory responses offering protection against stress, promoting growth of neuronal processes (neurites and re-establishment of synapses. The transcription of a key gene in the neurite growth network, the kinase Ptk2b, was significantly up-regulated in Tg mice as was the activated (phosphorylated form of the protein. In addition to genes related to neurite growth and synaptic development, those associated with neuronal vesicle trafficking in the Huntington's disease signalling pathway, were also up-regulated. Conclusions This is the first study attempting to define neuronal gene expression patterns in response to chronic, endogenous Glu hyperactivity at brain synapses. The patterns observed were characterized by a combination of responses to stress and stimulation of nerve growth, intracellular transport and recovery.

  17. The Association study of nonsyndromic cleft lip with or without cleft ...

    Indian Academy of Sciences (India)

    Navya

    2016-11-25

    Nov 25, 2016 ... These authors contributed equally to this work. .... individuals without a family history of orofacial clefts or other major congenital defects. ..... Wehby G. L., Cassell C. H. 2010 The impact of orofacial clefts on quality of life and.

  18. Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

    Science.gov (United States)

    Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

    2010-12-20

    Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

  19. Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Liu

    2010-12-01

    Full Text Available Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP and long-term depression (LTD. Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses of the midbrain ventral tegmental area (VTA following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids, the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

  20. Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

    Science.gov (United States)

    Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

    2010-01-01

    Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction. PMID:21187978

  1. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  2. Risk of oral clefts in children born to mothers taking Topamax (topiramate)Risk of Oral Clefts (Cleft Lip and/or ...

    Science.gov (United States)

    ... Drug Safety and Availability FDA Drug Safety Communication: Risk of oral clefts in children born to mothers ... data that show that there is an increased risk for the development of cleft lip and/or ...

  3. Mitochondrial dysfunction associated with nitric oxide pathways in glutamate neurotoxicity.

    Science.gov (United States)

    Manucha, Walter

    Multiple mechanisms underlying glutamate-induced neurotoxicity have recently been discussed. Likewise, a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with neurodegeneration, oxidative stress, and inflammation. This article highlights nitric oxide, an atypical neurotransmitter synthesized and released on demand by the post-synaptic neurons, and has many important implications for nerve cell survival and differentiation. Consequently, synaptogenesis, synapse elimination, and neurotransmitter release, are nitric oxide-modulated. Interesting, an emergent role of nitric oxide pathways has been discussed as regards neurotoxicity from glutamate-induced apoptosis. These findings suggest that nitric oxide pathways modulation could prevent oxidative damage to neurons through apoptosis inhibition. This review aims to highlight the emergent aspects of nitric oxide-mediated signaling in the brain, and how they can be related to neurotoxicity, as well as the development of neurodegenerative diseases development. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Knockout of GAD65 has major impact on synaptic GABA synthesized from astrocyte-derived glutamine

    DEFF Research Database (Denmark)

    Walls, Anne Byriel; Eyjolfsson, Elvar M.; Smeland, Olav B.

    2011-01-01

    γ-Aminobutyric acid (GABA) synthesis from glutamate is catalyzed by glutamate decarboxylase (GAD) of which two isoforms, GAD65 and GAD67, have been identified. The GAD65 has repeatedly been shown to be important during intensified synaptic activity. To specifically elucidate the significance of G...... glutamine both via direct synthesis and via a pathway involving mitochondrial metabolism. Furthermore, a severe neuronal hypometabolism, involving glycolysis and tricarboxylic acid (TCA) cycle activity, was observed in cerebral cortex of GAD65 knockout mice.......65 for maintenance of the highly compartmentalized intracellular and intercellular GABA homeostasis, GAD65 knockout and corresponding wild-type mice were injected with [1-(13)C]glucose and the astrocyte-specific substrate [1,2-(13)C]acetate. Synthesis of GABA from glutamine in the GABAergic synapses...

  5. Isolated cleft palate requires different surgical protocols depending on cleft type.

    Science.gov (United States)

    Elander, Anna; Persson, Christina; Lilja, Jan; Mark, Hans

    2017-08-01

    A staged protocol for isolated cleft palate (CPO), comprising the early repair of the soft palate at 6 months and delayed repair of the eventual cleft in the hard palate until 4 years, designed to improve maxillary growth, was introduced. CPO is frequently associated with additional congenital conditions. The study evaluates this surgical protocol for clefts in the soft palate (CPS) and for clefts in the hard and soft palate (CPH), with or without additional malformation, regarding primary and secondary surgical interventions needed for cleft closure and for correction of velopharyngeal insufficiency until 10 years of age. Of 94 consecutive children with CPO, divided into four groups with (+) or without (-) additional malformations (CPS + or CPS - and CPH + or CPH-), hard palate repair was required in 53%, performed with small local flaps in 21% and with bilateral mucoperiosteal flaps in 32%. The total incidence of soft palate re-repair was 2% and the fistula repair of the hard palate was 5%. The total incidence of secondary velopharyngeal surgery was 17% until 10 years, varying from 0% for CPS - and 15% for CPH-, to 28% for CPS + and 30% for CPH+. The described staged protocol for repair of CPO is found to be safe in terms of perioperative surgical results, with comparatively low need for secondary interventions. Furthermore, the study indicates that the presence of a cleft in the hard palate and/or additional conditions have a negative impact on the development of the velopharyngeal function.

  6. An investigation of interactions between hypocretin/orexin signaling and glutamate receptor surface expression in the rat nucleus accumbens under basal conditions and after cocaine exposure.

    Science.gov (United States)

    Plaza-Zabala, Ainhoa; Li, Xuan; Milovanovic, Mike; Loweth, Jessica A; Maldonado, Rafael; Berrendero, Fernando; Wolf, Marina E

    2013-12-17

    Hypocretin peptides are critical for the effects of cocaine on excitatory synaptic strength in the ventral tegmental area (VTA). However, little is known about their role in cocaine-induced synaptic plasticity in the nucleus accumbens (NAc). First, we tested whether hypocretin-1 by itself could acutely modulate glutamate receptor surface expression in the NAc, given that hypocretin-1 in the VTA reproduces cocaine's effects on glutamate transmission. We found no effect of hypocretin-1 infusion on AMPA or NMDA receptor surface expression in the NAc, measured by biotinylation, either 30 min or 3h after the infusion. Second, we were interested in whether changes in hypocretin receptor-2 (Hcrtr-2) expression contribute to cocaine-induced plasticity in the NAc. As a first step towards addressing this question, Hcrtr-2 surface expression was compared in the NAc after withdrawal from extended-access self-administration of saline (control) versus cocaine. We found that surface Hcrtr-2 levels remain unchanged following 14, 25 or 48 days of withdrawal from cocaine, a time period in which high conductance GluA2-lacking AMPA receptors progressively emerge in the NAc. Overall, our results fail to support a role for hypocretins in acute modulation of glutamate receptor levels in the NAc or a role for altered Hcrtr-2 expression in withdrawal-dependent synaptic adaptations in the NAc following cocaine self-administration. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Ectrodactyly-ectodermal dysplasia clefting syndrome (EEC syndrome).

    Science.gov (United States)

    Koul, Monika; Dwivedi, Rahul; Upadhyay, Vinod

    2014-01-01

    Ectrodactyly-ectodermal dysplasia- clefting syndrome (also k/a. split hand- split foot malformation /split hand-split foot ectodermal dysplasia- cleft syndrome/ectodermal dysplasia cleft lip/cleft palate syndrome) a rare form of ectodermal dysplasia, is an autosomal dominant disorder inherited as a genetic trait and characterized by a triad of (i) ectrodactyly, (ii) ectodermal dysplasia and, (iii) & facial clefts.

  8. Ectrodactyly-ectodermal dysplasia clefting syndrome (EEC syndrome)

    OpenAIRE

    Koul, Monika; Dwivedi, Rahul; Upadhyay, Vinod

    2014-01-01

    Ectrodactyly-ectodermal dysplasia- clefting syndrome (also k/a. split hand- split foot malformation /split hand-split foot ectodermal dysplasia- cleft syndrome/ectodermal dysplasia cleft lip/cleft palate syndrome) a rare form of ectodermal dysplasia, is an autosomal dominant disorder inherited as a genetic trait and characterized by a triad of (i) ectrodactyly, (ii) ectodermal dysplasia and, (iii) & facial clefts.

  9. Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers.

    Science.gov (United States)

    Yuzaki, Michisuke

    2010-07-01

    Several C1q family members, especially the Cbln and C1q-like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)-Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF-Purkinje cell synaptogenesis in vitro and in vivo. Antigen-unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer. © The Author (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  10. The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region☆

    Science.gov (United States)

    Xu, Qiuling; Liu, Tao; Chen, Shuping; Gao, Yonghui; Wang, Junying; Qiao, Lina; Liu, Junling

    2012-01-01

    In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. PMID:25657670

  11. Association of single nucleotide polymorphisms in WNT genes with the risk of nonsyndromic cleft lip with or without cleft palate.

    Science.gov (United States)

    Rafighdoost, Houshang; Hashemi, Mohammad; Asadi, Hossein; Bahari, Gholamreza

    2018-01-22

    Nonsyndromic cleft lip with or without cleft palate is a common congenital deformity worldwide with multifaceted etiology. Interaction of genes and environmental factors has been indicated to be related with susceptibility to nonsyndromic cleft lip with or without cleft palate. Some WNT genes which are involved in craniofacial embryogenesis may play a key role in the pathogenesis of nonsyndromic cleft lip with or without cleft palate. In the present study, we aimed to inspect the relationship between WNT3 (rs3809857 and rs9890413), WNT3A (rs752107 and rs3121310), and WNT10a rs201002930 (c.392 C>T) polymorphisms and nonsyndromic cleft lip with or without cleft palate in an Iranian population. The present case-control study was carried out on 120 unrelated nonsyndromic cleft lip with or without cleft palate patients and 112 healthy subjects. The variants were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. The findings suggest that the rs3809857 polymorphism significantly decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.16, 95% confidence interval = 0.03-0.75, P = 0.020, TT vs GG), recessive (odds ratio = 0.16, 95% confidence interval = 0.03-0.72, P = 0.009, TT vs GG + GT) inheritance models. The rs9890413 variant marginally decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.41, 95% confidence interval = 0.17-0.99, P = 0.047, AG vs AA) model. Regarding C392T variant, the findings revealed that this variant significantly decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.24, 95% confidence interval = 0.10-0.58, P = 0.002, CT vs CC) and allele (odds ratio = 0.26, 95% confidence interval = 0.11-0.62, P = 0.002, T vs C) models. No significant association was observed between the rs752107 and rs3121310 variants

  12. Cleft characteristics and treatment outcomes in hemifacial microsomia compared to non-syndromic cleft lip/palate.

    Science.gov (United States)

    Dentino, K M; Valstar, A; Padwa, B L

    2016-06-01

    The goal of this study was to describe the clinical characteristics and treatment outcomes of patients with hemifacial microsomia (HFM) and cleft lip/palate (CL/P), and to compare them to a historic cohort of patients with non-syndromic CL/P treated at the same centre. A retrospective review of patients with HFM and CL/P was performed; the main outcome measures assessed were cleft type/side, surgical outcome, midfacial retrusion, and speech. Twenty-six patients (13 male, 13 female; mean age 22.7±14.9, range 1-52 years) with cleft lip with/without cleft palate (CL±P) were identified: three with cleft lip (12%), two with cleft lip and alveolus and an intact secondary palate (8%), and 21 with cleft lip and palate (CLP) (81%; 15 unilateral and six bilateral). Four patients (19%) had a palatal fistula after palatoplasty. Twelve of 22 patients aged >5 years (55%) had midfacial retrusion and two (9%) required a pharyngeal flap for velopharyngeal insufficiency (VPI). Fisher's exact test demonstrated a higher frequency of complete labial clefting (P=0.004), CLP (P=0.009), midfacial retrusion (P=0.0009), and postoperative palatal fistula (P=0.03) in HFM compared to non-syndromic CL±P. There was no difference in VPI prevalence. This study revealed that patients with HFM and CL±P have more severe forms of orofacial clefting than patients with non-syndromic CL±P. Patients with HFM and CL±P have more severe midfacial retrusion and a higher palatal fistula rate compared to patients with non-syndromic CL±P. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Pu-erh Tea Protects the Nervous System by Inhibiting the Expression of Metabotropic Glutamate Receptor 5.

    Science.gov (United States)

    Li, Chunjie; Chai, Shaomeng; Ju, Yongzhi; Hou, Lu; Zhao, Hang; Ma, Wei; Li, Tian; Sheng, Jun; Shi, Wei

    2017-09-01

    Glutamate is one of the major excitatory neurotransmitters of the CNS and is essential for numerous key neuronal functions. However, excess glutamate causes massive neuronal death and brain damage owing to excitotoxicity via the glutamate receptors. Metabotropic glutamate receptor 5 (mGluR5) is one of the glutamate receptors and represents a promising target for studying neuroprotective agents of potential application in neurodegenerative diseases. Pu-erh tea, a fermented tea, mainly produced in Yunnan province, China, has beneficial effects, including the accommodation of the CNS. In this study, pu-erh tea markedly decreased the transcription and translation of mGluR5 compared to those by black and green teas. Pu-erh tea also inhibited the expression of Homer, one of the synaptic scaffolding proteins binding to mGluR5. Pu-erh tea protected neural cells from necrosis via blocked Ca 2+ influx and inhibited protein kinase C (PKC) activation induced by excess glutamate. Pu-erh tea relieved rat epilepsy induced by LiCl-pilocarpine in behavioural and physiological assays. Pu-erh tea also decreased the expression of mGluR5 in the hippocampus. These results show that the inhibition of mGluR5 plays a role in protecting neural cells from glutamate. The results also indicate that pu-erh tea contains biological compounds binding transcription factors and inhibiting the expression of mGluR5 and identify pu-erh tea as a novel natural neuroprotective agent.

  14. Surgical repair of large cyclodialysis clefts.

    Science.gov (United States)

    Gross, Jacob B; Davis, Garvin H; Bell, Nicholas P; Feldman, Robert M; Blieden, Lauren S

    2017-05-11

    To describe a new surgical technique to effectively close large (>180 degrees) cyclodialysis clefts. Our method involves the use of procedures commonly associated with repair of retinal detachment and complex cataract extraction: phacoemulsification with placement of a capsular tension ring followed by pars plana vitrectomy and gas tamponade with light cryotherapy. We also used anterior segment optical coherence tomography (OCT) as a noninvasive mechanism to determine the extent of the clefts and compared those results with ultrasound biomicroscopy (UBM) and gonioscopy. This technique was used to repair large cyclodialysis clefts in 4 eyes. All 4 eyes had resolution of hypotony and improvement of visual acuity. One patient had an intraocular pressure spike requiring further surgical intervention. Anterior segment OCT imaging in all 4 patients showed a more extensive cleft than UBM or gonioscopy. This technique is effective in repairing large cyclodialysis clefts. Anterior segment OCT more accurately predicted the extent of each cleft, while UBM and gonioscopy both underestimated the size of the cleft.

  15. Lower lip deformity in patients with cleft and non-cleft Class III malocclusion before and after orthognathic surgery.

    Science.gov (United States)

    Park, Joo Seok; Koh, Kyung S; Choi, Jong Woo

    2015-10-01

    Orthognathic surgery does not yield the same cosmetic benefits in patients with Class III jaw deformities associated with clefts as for patients without clefts. Preoperative upper lip tightness caused by cleft lip repair may not fully explain this difference, suggesting that a lower lip deformity is present. The study compared the outcomes of orthognathic surgery in patients with cleft and non-cleft Class III malocclusion, focusing on lip relationship. The surgical records of 50 patients with Class III malocclusion, including 25 with and 25 without clefts, who had undergone orthognathic surgery, were retrospectively analyzed. Lateral cephalometric tracings, preoperatively and at 6 months postoperatively, were superimposed to analyze the soft tissue changes at seven reference points. At 6 months after surgery, there were no significant differences in skeletal location, whereas the soft tissues of the lower lip differed significantly between patients with and without cleft (p=0.002), indicating the persistence of a lower lip deformity in cleft patients. Moreover, the soft tissues of the lower lip receded in non-cleft patients and protruded in cleft patients after orthognathic surgery. Lower lip deformity and upper lip tightness may result in an unsatisfactory relationship between the upper and lower lips of patients with cleft-related jaw deformity after orthognathic surgery. Other factors were less important than the pathology of the lower lip. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Clinical Study of Second Branchial Cleft Anomalies.

    Science.gov (United States)

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2018-03-30

    The objective of this study was to review the clinical characteristics and surgical treatment outcomes of second branchial cleft anomalies, and to evaluate the usefulness and accuracy of preoperative fine-needle aspiration cytology (FNAC) in the diagnosis of branchial cleft cysts. A retrospective chart review was performed at Chonnam National University Hwasun Hospital from January 2010 to December 2016. Among 25 patients with second branchial cleft anomalies, in 23 patients (92.0%), these anomalies presented as cysts, and in the remaining 2 patients (8.0%), these anomalies presented as fistulas. Fine-needle aspiration cytology had a diagnostic sensitivity of 100%, a positive-predictive value of 100%, and accuracy of 100% for diagnosing second branchial cleft cyst. All patients of second branchial cleft anomalies were treated surgically under general anesthesia. No recurrence of second branchial cleft anomalies was observed. Branchial cleft cysts were the most common type of second branchial cleft anomalies. Preoperative FNAC is a useful and accurate method for preoperative evaluation of branchial cleft cysts. Surgical excision of second branchial cleft anomalies is the treatment of choice without any complications and with no recurrence.

  17. A Relationship between nasolabial appearance and self-esteem in adolescent with repaired cleft lip and cleft palate at Khon Kaen University Cleft Center.

    Science.gov (United States)

    Patjanasoontornm, Niramol; Wongniyom, Kusalapom; Pradubwong, Suteera; Piyavhakul, Navanant; Chowchuen, Bowornsilp

    2014-10-01

    To examine levels of self-esteem of adolescents with repaired cleft lip and cleft palate at Khon Kaen University Cleft Center and its correlation with nasolabial appearance. Across-sectional survey of 93 adolescents with repaired cleft lip and palate. A total nasolabial appearance score was 2.8 +/- 0.36 (fair to good). The mean of the total self-esteem score for all respondents was 20.11 +/- 3.27 (maximum 30). There was no-significant correlation between nasolabial appearance and self esteem (Pearson product-moment correlation coefficiency (r) = 0.18, p = 0.08. The self-esteem scores of good, fair and poor appearance were 20.5 +/- 0.98, 19.8 +/- 0.32, 19 +/- 2.09 respectively. The nasolabial appearance of repaired cleft lip and palate not be the only factor but other psychosocialfactors also may play a role in their self-esteem. The analysis of this study found no relationship between self-esteem and appearance.

  18. Cleft Lip – A Comprehensive Review

    OpenAIRE

    Shkoukani, Mahdi A.; Chen, Michael; Vong, Angela

    2013-01-01

    Orofacial clefts comprise a range of congenital deformities and are the most common head and neck congenital malformation. Clefting has significant psychological and socio- economic effects on patient quality of life and require a multidisciplinary team approach for management. The complex interplay between genetic and environmental factors play a significant role in the incidence and cause of clefting. In this review, the embryology, classification, epidemiology, and etiology of cleft lip ar...

  19. Current surgical practices in cleft care: cleft palate repair techniques and postoperative care.

    Science.gov (United States)

    Katzel, Evan B; Basile, Patrick; Koltz, Peter F; Marcus, Jeffrey R; Girotto, John A

    2009-09-01

    The purpose of this study was to objectively report practices commonly used in cleft palate repair in the United States. This study investigates current surgical techniques, postoperative care, and complication rates for cleft palate repair surgery. All 803 surgeon members of the American Cleft Palate-Craniofacial Association were sent online and/or paper surveys inquiring about their management of cleft palate patients. Three-hundred six surveys were received, a 38 percent response rate. This represented responses of surgeons from 100 percent of American Cleft Palate-Craniofacial Association registered cleft teams. Ninety-six percent of respondents perform a one-stage repair. Eighty-five percent of surgeons perform palate surgery when the patient is between 6 and 12 months of age. The most common one-stage repair techniques are the Bardach style (two flaps) with intravelar veloplasty and the Furlow palatoplasty. After surgery, 39 percent of surgeons discharge patients within 24 hours. Another 43 percent discharge patients within 48 hours. During postoperative management, 92 percent of respondents implement feeding restrictions. Eighty-five percent of physicians use arm restraints. Surgeons' self-reported complications rates are minimal: 54 percent report a fistula in less than 5 percent of cases. The reported need for secondary speech surgery varies widely. The majority of respondents repair clefts in one stage. The most frequently used repair techniques are the Furlow palatoplasty and the Bardach style with intravelar veloplasty. After surgery, the majority of surgeons discharge patients in 1 or 2 days, and nearly all surgeons implement feeding restrictions and the use of arm restraints. The varying feeding protocols are reviewed in this article.

  20. Cranio-facial clefts in pre-hispanic America.

    Science.gov (United States)

    Marius-Nunez, A L; Wasiak, D T

    2015-10-01

    Among the representations of congenital malformations in Moche ceramic art, cranio-facial clefts have been portrayed in pottery found in Moche burials. These pottery vessels were used as domestic items during lifetime and funerary offerings upon death. The aim of this study was to examine archeological evidence for representations of cranio-facial cleft malformations in Moche vessels. Pottery depicting malformations of the midface in Moche collections in Lima-Peru were studied. The malformations portrayed on pottery were analyzed using the Tessier classification. Photographs were authorized by the Larco Museo.Three vessels were observed to have median cranio-facial dysraphia in association with midline cleft of the lower lip with cleft of the mandible. ML001489 portrays a median cranio-facial dysraphia with an orbital cleft and a midline cleft of the lower lip extending to the mandible. ML001514 represents a median facial dysraphia in association with an orbital facial cleft and a vertical orbital dystopia. ML001491 illustrates a median facial cleft with a soft tissue cleft. Three cases of midline, orbital and lateral facial clefts have been portrayed in Moche full-figure portrait vessels. They represent the earliest registries of congenital cranio-facial malformations in ancient Peru. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.

    Science.gov (United States)

    Marsman, Anouk; Mandl, René C W; Klomp, Dennis W J; Bohlken, Marc M; Boer, Vincent O; Andreychenko, Anna; Cahn, Wiepke; Kahn, René S; Luijten, Peter R; Hulshoff Pol, Hilleke E

    2014-01-01

    Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.

  2. Early correction of septum JJ deformity in unilateral cleft lip-cleft palate.

    Science.gov (United States)

    Morselli, Paolo G; Pinto, Valentina; Negosanti, Luca; Firinu, Antonella; Fabbri, Erich

    2012-09-01

    The treatment of patients affected by unilateral cleft lip-cleft palate is based on a multistage procedure of surgical and nonsurgical treatments in accordance with the different types of deformity. Over time, the surgical approach for the correction of a nasal deformity in a cleft lip-cleft palate has changed notably and the protocol of treatment has evolved continuously. Not touching the cleft lip nose in the primary repair was dogmatic in the past, even though this meant severe functional, aesthetic, and psychological problems for the child. McComb reported a new technique for placement of the alar cartilage during lip repair. The positive results of this new approach proved that the early correction of the alar cartilage anomaly is essential for harmonious facial growth with stable results and without discomfort for the child. The authors applied the same principles used for the treatment of the alar cartilage for correction of the septum deformity, introducing a primary rhinoseptoplasty during the cheiloplasty. The authors compared two groups: group A, which underwent septoplasty during cleft lip repair; and group B, which did not. After the anthropometric evaluation of the two groups, the authors observed better symmetry regarding nasal shape, correct growth of the nose, and a strong reduction of the nasal deformity in the patients who underwent primary JJ septum deformity correction. The authors can assume that, similar to the alar cartilage, the septum can be repositioned during the primary surgery, without causing growth anomaly, improving the morphologic/functional results.

  3. Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate

    DEFF Research Database (Denmark)

    Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R

    2017-01-01

    Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common human birth defects with complex etiology. Although genome-wide association studies have successfully identified a number of risk loci, these loci only account for about 20% of the heritability of orofacial clefts. ...

  4. Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats

    International Nuclear Information System (INIS)

    Krueger, Katharina; Straub, Heidrun; Hirner, Alfred V.; Hippler, Joerg; Binding, Norbert; Musshoff, Ulrich

    2009-01-01

    Arsenite and its metabolites, dimethylarsinic or dimethylarsinous acid, have previously been shown to disturb synaptic transmission in hippocampal slices of rats (Krueger, K., Gruner, J., Madeja, M., Hartmann, L.M., Hirner, A.V., Binding, N., Muβhoff, U., 2006a. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals. Arch. Toxicol. 80, 492-501, Krueger, K., Straub, H., Binding, N., Muβhoff, U., 2006b. Effects of arsenite on long-term potentiation in hippocampal slices from adult and young rats. Toxicol. Lett. 165, 167-173, Krueger, K., Repges, H., Hippler, J., Hartmann, L.M., Hirner, A.V., Straub, H., Binding, N., Muβhoff, U., 2007. Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats. Toxicol. Appl. Pharmacol. 225, 40-46). The present experiments investigate, whether the important arsenic metabolites monomethylarsonic acid (MMA V ) and monomethylarsonous acid (MMA III ) also influence the synaptic functions of the hippocampus. In hippocampal slices of young (14-21 days-old) and adult (2-4 months-old) rats, evoked synaptic field potentials from the Schaffer collateral-CA1 synapse were measured under control conditions and during and after 30 and 60 min of application of the arsenic compounds. MMA V had no effect on the synapse functions neither in slices of adult nor in those from young rats. However, MMA III strongly influenced the synaptic transmission: it totally depressed the amplitudes of fEPSPs at concentrations of 50 μmol/l (adult rats) and 25 μmol/l (young rats) and LTP amplitudes at concentrations of 25 μmol/l (adult rats) and 10 μmol/l (young rats), respectively. In contrast, application of 1 μmol/l MMA III led to an enhancement of the LTP amplitude in young rats, which is interpretable by an enhancing effect on NMDA receptors and a lack of the blocking effect on AMPA receptors at this concentration (Krueger, K., Gruner, J

  5. Incidence of Cleft Lip and Palate in Uganda

    NARCIS (Netherlands)

    Dreise, Marieke; Galiwango, George; Hodges, Andrew

    Objective: The purpose of the study was to estimate the need for resources for cleft repairs in Uganda by determining the overall incidence of oral-facial clefts and the ratio of isolated cleft lip to isolated cleft palate to cleft lip and palate. Design: A 1-year prospective study was implemented

  6. Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures

    Science.gov (United States)

    Koizumi, Schuichi; Fujishita, Kayoko; Tsuda, Makoto; Shigemoto-Mogami, Yukari; Inoue, Kazuhide

    2003-09-01

    Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca2+ transients in astrocytes, and Ca2+ transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bidirectional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca2+ signaling among astrocytes, also mediates intercellular signaling between astrocytes and neurons in hippocampal cultures. Mechanical stimulation of astrocytes evoked Ca2+ waves mediated by the release of ATP and the activation of P2 receptors. Mechanically evoked Ca2+ waves led to decreased excitatory glutamatergic synaptic transmission in an ATP-dependent manner. Exogenous application of ATP does not affect postsynaptic glutamatergic responses but decreased presynaptic exocytotic events. Finally, we show that astrocytes exhibit spontaneous Ca2+ waves mediated by extracellular ATP and that inhibition of these Ca2+ responses enhanced excitatory glutamatergic transmission. We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via presynaptic mechanisms.

  7. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

    Directory of Open Access Journals (Sweden)

    Andrew T Kempsell

    2015-09-01

    Full Text Available Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature versus advanced age Aplysia. Glutamate- (L-Glu- evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT in sensory neurons (SN isolated from mature but not aged animals. Activation of PKA and PKC signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems

  8. CLEFT PALATE. FOUNDATIONS OF SPEECH PATHOLOGY SERIES.

    Science.gov (United States)

    RUTHERFORD, DAVID; WESTLAKE, HAROLD

    DESIGNED TO PROVIDE AN ESSENTIAL CORE OF INFORMATION, THIS BOOK TREATS NORMAL AND ABNORMAL DEVELOPMENT, STRUCTURE, AND FUNCTION OF THE LIPS AND PALATE AND THEIR RELATIONSHIPS TO CLEFT LIP AND CLEFT PALATE SPEECH. PROBLEMS OF PERSONAL AND SOCIAL ADJUSTMENT, HEARING, AND SPEECH IN CLEFT LIP OR CLEFT PALATE INDIVIDUALS ARE DISCUSSED. NASAL RESONANCE…

  9. Not All Clefts Are Created Equal: Patterns of Hospital-Based Care Use among Children with Cleft Lip and Palate within 4 Years of Initial Surgery.

    Science.gov (United States)

    Ligh, Cassandra A; Fox, Justin P; Swanson, Jordan; Yu, Jason W; Taylor, Jesse A

    2016-06-01

    This study compares hospital-based care and associated charges among children with cleft lip, cleft palate, or both, and identifies subgroups generating the greatest cumulative hospital charges. The authors conducted a retrospective cohort study of cleft lip, cleft palate, or cleft lip and palate who underwent initial surgery from 2006 to 2008 in four U.S. states. Primary outcome was hospital-based care-emergency, outpatient, inpatient-within 4 years of surgery. Regression models compared outcomes and classification tree analysis identified patients at risk for being in the highest quartile of cumulative hospital charges. The authors identified 4571 children with cleft lip (18.2 percent), cleft palate (39.2 percent), or cleft lip and palate (42.6 percent). Medical comorbidity was frequent across all groups, with feeding difficulty (cleft lip, 2.4 percent; cleft palate, 13.4 percent; cleft lip and palate, 6.0 percent; p cleft lip, 1.8 percent; cleft palate, 9.4 percent; cleft lip and palate, 3.6 percent; p cleft palate were most likely to return to the hospital (p cleft lip group, yet comparable among those with cleft palate and cleft lip and palate (p cleft palate cohort (cleft lip, $56,966; cleft palate, $106,090; cleft lip and palate, $91,263; p cleft lip versus cleft palate with or without cleft lip), and age at initial surgery were the most important factors associated with the highest quartile of cumulative hospital charges. Cleft lip and palate children experience a high rate of hospital-based care early in life, with degree of medical comorbidity being a significant burden. Understanding this relationship and associated needs may help deliver more efficient, patient-centered care.

  10. Comparative Assessment of the Cleft Profile by Patients with Cleft Lip and Palate, Cleft Surgeons, and Lay People.

    Science.gov (United States)

    Meng, Tian; Ma, Lian; Wang, Zhi

    2015-10-01

    This cross-sectional study aimed to compare subjective assessments among patients with cleft lip and palate (CLP), cleft surgeons, and lay people regarding the soft tissue lateral profile of CLP patients. We also investigated the correlations between subjective assessments and photogrammetric measurements. A total of 150 CLP patients who wished to have treatment for their unattractive appearance were randomly selected. A standard lateral profile color photograph was taken. Panels of three cleft surgeons, ten CLP patients, and ten lay people were selected to be assessors. They rated nasal tip projection, nasolabial esthetics, upper and lower lip esthetics, and the profile for each photograph. Three angular measurements (nasal prominence angle, nasolabial angle, and lip angle) were measured for each photograph. Kendall's coefficient of concordance and logistic regression were used for statistical analysis. Kendall's coefficient of concordance of nasal tip projection, nasolabial esthetics, upper and lower lip esthetics, and the profile were 0.734, 0.683, 0.828, and 0.747, respectively (p lay people (p lay people have similar attitudes to the appearance of CLP patients. Upper and lower lip esthetics is associated with the assessment of the cleft profile that is provided by CLP patients, cleft surgeons, and lay people. In addition, nasal tip projection is another determining factor for lay people. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  11. Targeting Glia with N-Acetylcysteine Modulates Brain Glutamate and Behaviors Relevant to Neurodevelopmental Disorders in C57BL/6J Mice

    Science.gov (United States)

    Durieux, Alice M. S.; Fernandes, Cathy; Murphy, Declan; Labouesse, Marie Anais; Giovanoli, Sandra; Meyer, Urs; Li, Qi; So, Po-Wah; McAlonan, Grainne

    2015-01-01

    An imbalance between excitatory (E) glutamate and inhibitory (I) GABA transmission may underlie neurodevelopmental conditions such as autism spectrum disorder (ASD) and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here, we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC), which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviors relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span. PMID:26696857

  12. Targeting glia with N-Acetylcysteine modulates brain glutamate and behaviours relevant to neurodevelopmental disorders in C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Alice Marie Sybille Durieux

    2015-12-01

    Full Text Available An imbalance between excitatory (E glutamate and inhibitory (I GABA transmission may underlie neurodevelopmental conditions such as Autism Spectrum Disorder (ASD and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC, which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in-vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviours relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span.

  13. Pharmacological or genetic orexin 1 receptor inhibition attenuates MK-801 induced glutamate release in mouse cortex

    Directory of Open Access Journals (Sweden)

    Leah eAluisio

    2014-05-01

    Full Text Available The orexin/hypocretin neuropeptides are produced by a cluster of neurons within the lateral posterior hypothalamus and participate in neuronal regulation by activating their receptors (OX1 and OX2 receptors. The orexin system projects widely through the brain and functions as an interface between multiple regulatory systems including wakefulness, energy balance, stress, reward and emotion. Recent studies have demonstrated that orexins and glutamate interact at the synaptic level and that orexins facilitate glutamate actions. We tested the hypothesis that orexins modulate glutamate signaling via OX1 receptors by monitoring levels of glutamate in frontal cortex of freely moving mice using enzyme coated biosensors under inhibited OX1 receptor conditions. MK-801, an NMDA receptor antagonist, was administered subcutaneously (0.178 mg/kg to indirectly disinhibit pyramidal neurons and therefore increase cortical glutamate release. In wild-type mice, pretreatment with the OX1 receptor antagonist GSK-1059865 (10 mg/kg S.C. which had no effect by itself, significantly attenuated the cortical glutamate release elicited by MK-801. OX1 receptor knockout mice had a blunted glutamate release response to MK-801 and exhibited about half of the glutamate release observed in wild-type mice in agreement with the data obtained with transient blockade of OX1 receptors. These results indicate that pharmacological (transient or genetic (permanent inhibition of the OX1 receptor similarly interfere with glutamatergic function in the cortex. Selectively targeting the OX1 receptor with an antagonist may normalize hyperglutamatergic states and thus may represent a novel therapeutic strategy for the treatment of various psychiatric disorders associated with hyperactive states.

  14. Unusual case of cleft hand

    Directory of Open Access Journals (Sweden)

    Sahasrabudhe Parag

    2007-01-01

    Full Text Available We present a case of a six-year-old male child with cleft hand deformity involving the dominant right hand. It was a rare case of atypical cleft hand with no missing tissue but cleft extending to metacarpal level and associated hypoplasia of thumb and index finger. As per Manske′s classification of cleft hand our patient belongs to the Class III variety. There was associated malposition of the index finger with absence of first web space and syndactly of thumb and index finger at the metacarpal level. A modified Snow-Littler procedure was planned. The surgical plan involved closure of cleft, release of thumb and index finger syndactly and reconstruction of the first web space. The functional outcome was good considering hypoplasia of the index finger and thumb. Depending upon the function of the thumb tendon transfers can be planned to augment thumb function at a later date along with correction of rotational deformities of the index and middle finger.

  15. Effect of Low Level Laser Irradiation at Wavelengths 488 and 515 nm on Glutamate Neurotransmitter in Mitochondria of Visual Brain Cortex in Albino Rat

    International Nuclear Information System (INIS)

    Omran, M.F.; El-Ahdal, M.A.; El-Kady, M.H.; Yousri, R.M.

    2004-01-01

    The presence of glutamate in the visual cortex and mitochondria could be used as a measure for the argon laser effect having wavelengths 488 and 515 nm, on the mitochondria. A comparative response for the bound and free glutamate was found. Irradiation with different energies 0.2, 0.5 and 1.0 J for both wavelengths were accomplished. This study makes us to recommend the advantage of using argon laser having wavelength 515 nm to enhance the blocking of glutamate and hence the reduction of brain toxicity. Most of the energy required for cellular functions comes from mitochondria (Shepherd, 1994). Glutamate, which is present in central nervous system at very high level is essential for brain intermediary metabolism (Frazer et al., 1994; Meldrum et al., 2000 and Blumcke et al., 2000). Glutamate is enriched in synaptic vesicles, the subcellular organelles, which are associated with the storage and release of neurotransmitters. Also, biochemical evidence for glutamate as neurotransmitter in fibers from the visual cortex to the subcortical visual relay nuclei has been indicated (Fose and Fonnum, 1987 and George, 1998)

  16. Centre-based statistics of cleft lip with/without alveolus and palate as well as cleft palate only patients in Aden, Yemen.

    Science.gov (United States)

    Esmail, Ahlam Hibatulla Ali; Abdo, Muhgat Ahmed Ali; Krentz, Helga; Lenz, Jan-Hendrik; Gundlach, Karsten K H

    2014-06-01

    The purpose of the study was to report the types and patterns of cleft lip with/without cleft alveolus and palate as well as cleft palate only as seen in Aden, Yemen. Retrospective, centre-based study conducted at the Cleft Lip and Palate Centre, Aden University, Yemen. Statistical evaluation of the data from all cleft patients who were registered at or referred to this centre during the years 2005-2011. A total of 1110 cleft patients were seen during the period studied (2005-2011). Amongst these there were 183 (16.48%) with a cleft lip and 144 (12.98) with a cleft of lip and alveolus, 228 (20.54%) had a cleft palate, and 555 (50%) had a combination of cleft lip, alveolus, and palate. The clefts were found more often in males than in females (56.5% boys versus 43.5% girls). This difference was statistically significant (p ≤ 0.001). Statistically significant sex differences were also noted when evaluating the various cleft types. Isolated cleft palates were found most often in females. Among the cleft palate cases there were 102 (9.2%) with a cleft soft palate only. The ages of the patients were between one day and 40 years. Two hundred and one children (18%) had a positive family history of clefts. Among the risk factors considered in this study, consanguineous marriages among cousins were found most frequently (in 48% of the cases). In contrast to this, only 10% of the mothers had reported to have been taking medication directly prior to or during the first trimester of their pregnancy. On average the mothers were neither very young nor very old. The prevalence rate of orofacial cleft types among this Yemeni sample was similar to prevalence rates previously reported in white Caucasians. The present study did neither find many cases with medication before, nor during, pregnancy; there were few young or very old mothers; and the incidence of positive family histories was similar to those found in other studies on clefts. However, consanguineous marriages were

  17. 17β-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes.

    Science.gov (United States)

    Mitrović, Nataša; Zarić, Marina; Drakulić, Dunja; Martinović, Jelena; Sévigny, Jean; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana

    2017-03-01

    17β-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.

  18. Lower incidence of nonsyndromic cleft lip with or without cleft palate ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... In India, as in other parts of the world, nonsyndromic cleft lip with or without cleft palate (NSCL±P) is a highly prevalent birth defect, its incidence in males being twice that in females. A case–control association study has been carried out with respect to homocysteine level and MTHFR C677T, A1298C and ...

  19. The role of cAMP in synaptic homeostasis in response to environmental temperature challenges and hyperexcitability mutations

    Directory of Open Access Journals (Sweden)

    Atsushi eUeda

    2015-02-01

    Full Text Available Homeostasis is the ability of physiological systems to regain functional balance following environment or experimental insults and synaptic homeostasis has been demonstrated in various species following genetic or pharmacological disruptions. Among environmental challenges, homeostatic responses to temperature extremes are critical to animal survival under natural conditions. We previously reported that axon terminal arborization in Drosophila larval neuromuscular junctions is enhanced at elevated temperatures; however, the amplitude of excitatory junctional potentials (EJPs remains unaltered despite the increase in synaptic bouton numbers. Here we determine the cellular basis of this homeostatic adjustment in larvae reared at high temperature (HT, 29 ˚C. We found that synaptic current focally recorded from individual synaptic boutons was unaffected by rearing temperature (30 ˚C. However, HT rearing decreased the quantal size (amplitude of spontaneous miniature EJPs, or mEJPs, which compensates for the increased number of synaptic releasing sites to retain a normal EJP size. The quantal size decrease is accounted for by a decrease in input resistance of the postsynaptic muscle fiber, indicating an increase in membrane area that matches the synaptic growth at HT. Interestingly, a mutation in rutabaga (rut encoding adenylyl cyclase (AC exhibited no obvious changes in quantal size or input resistance of postsynaptic muscle cells after HT rearing, suggesting an important role for rut AC in temperature-induced synaptic homeostasis in Drosophila. This extends our previous finding of rut-dependent synaptic homeostasis in hyperexcitable mutants, e.g. slowpoke (slo. In slo larvae, the lack of BK channel function is partially ameliorated by upregulation of presynaptic Sh IA current to limit excessive transmitter release in addition to postsynaptic glutamate receptor recomposition that reduces the quantal size.

  20. Correlations between initial cleft size and dental anomalies in unilateral cleft lip and palate patients after alveolar bone grafting.

    Science.gov (United States)

    Jabbari, Fatima; Reiser, Erika; Thor, Andreas; Hakelius, Malin; Nowinski, Daniel

    2016-01-01

    Objective To determine in individuals with unilateral cleft lip and palate the correlation between initial cleft size and dental anomalies, and the outcome of alveolar bone grafting. Methods A total of 67 consecutive patients with non-syndromic unilateral complete cleft lip and palate (UCLP) were included from the cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. All patients were operated by the same surgeon and treated according to the Uppsala protocol entailing: lip plasty at 3 months, soft palate closure at 6 months, closure of the residual cleft in the hard palate at 2 years of age, and secondary alveolar bone grafting (SABG) prior to the eruption of the permanent canine. Cleft size was measured on dental casts obtained at the time of primary lip plasty. Dental anomalies were registered on radiographs and dental casts obtained before bone grafting. Alveolar bone height was evaluated with the Modified Bergland Index (mBI) at 1 and 10-year follow-up. Results Anterior cleft width correlated positively with enamel hypoplasia and rotation of the central incisor adjacent to the cleft. There was, however, no correlation between initial cleft width and alveolar bone height at either 1 or 10 years follow-up. Conclusions Wider clefts did not seem to have an impact on the success of secondary alveolar bone grafting but appeared to be associated with a higher degree of some dental anomalies. This finding may have implications for patient counseling and treatment planning.

  1. Hearing outcomes in patients with cleft lip/palate.

    Science.gov (United States)

    Skuladottir, Hildur; Sivertsen, Ase; Assmus, Jorg; Remme, Asa Rommetveit; Dahlen, Marianne; Vindenes, Hallvard

    2015-03-01

    Objective : Children with cleft lip and palate or cleft palate only have a high incidence of conductive hearing loss from otitis media with effusion. Studies demonstrating longitudinal results are lacking. This study was undertaken to investigate long-term longitudinal hearing outcomes of children with cleft lip and/or cleft palate and cleft palate only. Design : Retrospective chart review. Setting : Clinical charts of patients born with cleft lip and palate or cleft palate only in 1985 to 1994 who were referred to the cleft team in Bergen, Norway. Study findings include 15 years of follow-up. Participants : The study population consisted of 317 children of whom 159 had nonsyndromic cleft lip and palate and 158 had nonsyndromic cleft palate. Main Outcome Measures : Pure tone average calculated from pure tone audiometry at ages 4, 6, and 15 years. Results : The median pure tone average significantly improved with increasing age. For the cleft lip and palate group, the median pure tone average at ages 4, 6, and 15 years was 16 dB hearing level (HL), 13 dB HL, and 9 dB HL, respectively (P ≤ .001). In the cleft palate group the median pure tone average at ages 4, 6, and 15 years was 15 dB HL, 12 dB HL, and 9 dB HL, respectively (P ≤ .001). There was no significant difference in the hearing levels between the two groups. Patients who had surgical closure of the palate at age 18 months had a significantly better pure tone average outcome at age 15 compared with patients who had surgery at 12 months. Conclusions : Hearing improves significantly from childhood to adolescence in patients with cleft lip and palate and cleft palate only.

  2. The Fetal Cleft palate: V. Elucidation of the Mechanism of Palatal Clefting in the Congenital Caprine Model

    Science.gov (United States)

    Maternal ingestion of Nicotiana glauca from gestation days 32 through 41 results in a high incidence of cleft palate in Spanish goats. This caprine cleft palate model was used to evaluate the temporal sequence of palatal shelf fusion throughout the period of cleft induction with the poisonous plant...

  3. Cleft Lip and Palate

    Science.gov (United States)

    ... Cleft Lip or Cleft Palate Print en español Labio leporino y paladar hendido Tilt your head back a bit and look in the mirror. Do you see the way your nose connects to your upper lip? Now open your mouth. Do you see the ...

  4. Occlusal Classification in Relation to Original Cleft Width in Patients With Unilateral Cleft Lip and Palate.

    Science.gov (United States)

    Huang, Andrew H; Patel, Kamlesh B; Maschhoff, Clayton W; Huebener, Donald V; Skolnick, Gary B; Naidoo, Sybill D; Woo, Albert S

    2015-09-01

    To determine a correlation between the width of the cleft palate measured at the time of lip adhesion, definitive lip repair, and palatoplasty and the subsequent occlusal classification of patients born with unilateral cleft lip and palate. Retrospective, observational study. Referral, urban, children's hospital Participants : Dental models and records of 270 patients were analyzed. None. Angle occlusion classification. The mean age at which occlusal classification was determined was 11 ± 0.3 years. Of the children studies, 84 were diagnosed with Class I or II occlusion, 67 were diagnosed with Class III occlusion, and 119 were lost to follow up or transferred care. Mean cleft widths were significantly larger in subjects with Class III occlusion for all measures at time of lip adhesion and definitive lip repair (P cleft widths were significantly greater at the alveolus (P = .025) but not at the midportion of the hard palate (P = .35) or posterior hard palate (P = .10). Cleft widths from the lip through to the posterior hard palate are generally greater in children who are diagnosed with Class III occlusion later in life. Notably, the alveolar cleft width is significantly greater at each time point for patients who went on to develop Class III occlusion. There were no significant differences in cleft widths between patients diagnosed later with Class I and Class II occlusions.

  5. Genetic determinants of facial clefting: analysis of 357 candidate genes using two national cleft studies from Scandinavia.

    Directory of Open Access Journals (Sweden)

    Astanand Jugessur

    Full Text Available Facial clefts are common birth defects with a strong genetic component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped in two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark: 235 case-parent triads.We used two complementary statistical methods, TRIMM and HAPLIN, to look for associations across these two national samples. TRIMM tests for association in each gene by using multi-SNP genotypes from case-parent triads directly without the need to infer haplotypes. HAPLIN on the other hand estimates the full haplotype distribution over a set of SNPs and estimates relative risks associated with each haplotype. For isolated cleft lip with or without cleft palate (I-CL/P, TRIMM and HAPLIN both identified significant associations with IRF6 and ADH1C in both populations, but only HAPLIN found an association with FGF12. For isolated cleft palate (I-CP, TRIMM found associations with ALX3, MKX, and PDGFC in both populations, but only the association with PDGFC was identified by HAPLIN. In addition, HAPLIN identified an association with ETV5 that was not detected by TRIMM.Strong associations with seven genes were replicated in the Scandinavian samples and our approach effectively replicated the strongest previously known association in clefting--with IRF6. Based on two national cleft cohorts of similar ancestry, two robust statistical methods and a large panel of SNPs in the most promising cleft candidate genes to date, this study identified a previously unknown association with clefting for ADH1C and provides additional candidates and analytic approaches to advance the field.

  6. Distribution of AMPA-type glutamate receptor subunits in the chick visual system

    Directory of Open Access Journals (Sweden)

    Pires R.S.

    1997-01-01

    Full Text Available Several glutamate receptor (GluR subunits have been characterized during the past few years. In the present study, subunit-specific antisera were used to determine the distribution of the AMPA-type glutamate receptor subunits GluR1-4 in retinorecipient areas of the chick brain. Six white leghorn chicks (Gallus gallus, 7-15 days old, unknown sex were deeply anesthetized and perfused with 4% buffered paraformaldehyde and brain sections were stained using immunoperoxidase techniques. The AMPA-type glutamate receptor subunits GluR1, GluR2/3 and GluR4 were present in several retinorecipient areas, with varying degrees of colocalization. For example, perikarya in layers 2, 3, and 5 of the optic tectum contained GluR1, whereas GluR2/3 subunits appeared mainly in neurons of layer 13. The GluR4 subunit was only detected in a few cells of the tectal layer 13. GluR1 and GluR2/3 were observed in neurons of the nucleus geniculatus lateralis ventralis, whereas GluR4 was only present in its neuropil. Somata in the accessory optic nucleus appeared to contain GluR2/3 and GluR4, whereas GluR1 was the dominant subunit in the neuropil of this nucleus. These results suggest that different subpopulations of visual neurons might express different combinations of AMPA-type GluR subunits, which in turn might generate different synaptic responses to glutamate derived from retinal ganglion cell axons

  7. Dental fear in children with a cleft lip and/or cleft Palate

    NARCIS (Netherlands)

    Vogels, W.E.J.C.; Aartman, I.H.A.; Veerkamp, J.S.J.

    2011-01-01

    Objective: To assess the level of dental fear in children with a cleft lip and/or palate, to compare this level with that of a normative group testing the hypothesis that children with a cleft lip and/or palate have a higher level of dental anxiety than children from the general population, and to

  8. Nasal Airway Dysfunction in Children with Cleft Lip and Cleft Palate: Results of a Cross-Sectional Population-Based Study, with Anatomical and Surgical Considerations.

    Science.gov (United States)

    Sobol, Danielle L; Allori, Alexander C; Carlson, Anna R; Pien, Irene J; Watkins, Stephanie E; Aylsworth, Arthur S; Meyer, Robert E; Pimenta, Luiz A; Strauss, Ronald P; Ramsey, Barry L; Raynor, Eileen; Marcus, Jeffrey R

    2016-12-01

    The aesthetic aspects of the cleft lip nasal deformity have been appreciated for over a century, but the functional implications have remained largely underappreciated or misunderstood. This study describes the frequency and severity of nasal obstructive symptoms among children with cleft lip and/or cleft palate, addressing the hypotheses that age, cleft type, and severity are associated with the development of nasal obstructive symptoms. Children with nonsyndromic cleft lip and/or cleft palate and a comparison group of unaffected children born from 1997 to 2003 were identified through the North Carolina Birth Defects Monitoring Program and birth certificates. Nasal airway obstruction was measured using the validated Nasal Obstruction Symptom Evaluation scale. The survey was completed by parental proxy for 176 children with cleft lip and/or cleft palate and 333 unaffected children. Nasal obstructive symptoms were more frequently reported in cleft lip with cleft palate compared with unaffected children (p cleft lip with or without alveolus and isolated cleft palate were not statistically different from unaffected children. Patients with unilateral cleft lip with cleft palate were found to be more severely affected than bilateral cases. Nasal obstruction was observed in early childhood, although severity worsened in adolescence. This population-based study reports a high prevalence of nasal obstructive symptoms in children with cleft lip and/or cleft palate based on type and severity of the cleft. The authors encourage cleft teams to consider using this or similar screening methods to identify which children may benefit from functional rhinoplasty. Risk, I.

  9. Chronic ciguatoxin treatment induces synaptic scaling through voltage gated sodium channels in cortical neurons.

    Science.gov (United States)

    Martín, Víctor; Vale, Carmen; Rubiolo, Juan A; Roel, Maria; Hirama, Masahiro; Yamashita, Shuji; Vieytes, Mercedes R; Botana, Luís M

    2015-06-15

    Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long-term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate receptor expression in order to stabilize the overall activity. Immediate early genes, such as Arc and Egr1, are induced in response to activity changes and underlie the trafficking of glutamate receptors during neuronal homeostasis. To better understand the long lasting neurological consequences of ciguatera, it is important to establish the role that chronic changes in activity produced by ciguatoxins represent to central neurons. Here, the effect of a 30 min exposure of 10-13 days in vitro (DIV) cortical neurons to the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using real-time polymerase chain reaction approaches. Since the toxin increased the mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs), and glutamate receptors expression in cortical neurons after a 24 h exposure was evaluated using electrophysiological and western blot approaches. The data presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was prevented by previous coincubation of the neurons with the NaV channel blocker tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift in the activation voltage of NaV channels to more negative potentials and produced membrane potential depolarization. Moreover, 24 h treatment of cortical neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and downregulation in the protein level of glutamate receptors that was also prevented by tetrodotoxin

  10. The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region

    DEFF Research Database (Denmark)

    Tapken, Daniel; Steffensen, Thomas Bielefeldt; Leth, Rasmus

    2017-01-01

    Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D...

  11. GLT-1 Transport Stoichiometry Is Constant at Low and High Glutamate Concentrations when Chloride Is Substituted by Gluconate.

    Directory of Open Access Journals (Sweden)

    Anatoli Y Kabakov

    Full Text Available Glutamate is the major excitatory neurotransmitter, but prolonged exposure even at micromolar concentrations causes neuronal death. Extracellular glutamate is maintained at nanomolar level by glutamate transporters, which, however, may reverse transport and release glutamate. If and when the reverse occurs depends on glutamate transport stoichiometry (GTS. Previously we found that in the presence of chloride, the coupled GLT-1 glutamate transporter current and its relationship to radiolabeled glutamate flux significantly decreased when extracellular glutamate concentration increased above 0.2 mM, which implies a change in GTS. Such high concentrations are feasible near GLT-1 expressed close to synaptic release site during excitatory neurotransmission. The aim of this study was to determine GLT-1 GTS at both low (19-75 μM and high (300-1200 μM glutamate concentration ranges. GTS experiments were conducted in the absence of chloride to avoid contributions by the GLT-1 uncoupled chloride conductance. Mathematical analysis of the transporter thermodynamic equilibrium allowed us to derive equations revealing the number of a particular type of ion transported per elementary charge based on the measurements of the transporter reversal potential. We found that GLT-1a expressed in COS-7 cells co-transports 1.5 Na+, 0.5 Glu-, 0.5 H+ and counter-transports 0.6 K+ per elementary charge in both glutamate concentration ranges, and at both 37°C and 26°C temperatures. The thermodynamic parameter Q10 = 2.4 for GLT-1 turnover rate of 19 s-1 (37°C, -50 mV remained constant in the 10 μM-10 mM glutamate concentration range. Importantly, the previously reported decrease in the current/flux ratio at high glutamate concentration was not seen in the absence of chloride in both COS-7 cells and cultured rat neurons. Therefore, only in the absence of chloride, GLT-1 GTS remains constant at all glutamate concentrations. Possible explanations for why apparent GTS might

  12. Brain Injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons Is Differentially Suppressed by Rapamycin.

    Science.gov (United States)

    Butler, Corwin R; Boychuk, Jeffery A; Smith, Bret N

    2017-01-01

    Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in the somatostatinergic subset of hilar inhibitory interneurons, we tested the effect of daily systemic rapamycin treatment (3 mg/kg) on the excitability of hilar inhibitory interneurons after controlled cortical impact (CCI)-induced focal brain injury. Rapamycin treatment reduced, but did not normalize, the injury-induced increase in excitability of surviving eGFP+ hilar interneurons. The injury-induced increase in response to selective glutamate photostimulation of DGCs was reduced to normal levels after mTOR inhibition, but the postinjury increase in synaptic excitation arising from CA3 pyramidal cell activity was unaffected by rapamycin treatment. The incomplete suppression of synaptic reorganization in inhibitory circuits after brain injury could contribute to hippocampal hyperexcitability and the eventual reemergence of the epileptogenic process upon cessation of mTOR inhibition. Further, the cell-selective effect of mTOR inhibition on synaptic reorganization after CCI suggests possible mechanisms by which rapamycin treatment modifies epileptogenesis in some models but not others.

  13. Microbial methodological artifacts in [3H]glutamate receptor binding assays

    International Nuclear Information System (INIS)

    Yoneda, Y.; Ogita, K.

    1989-01-01

    Incubation of radiolabeled L-glutamic acid, a putative central excitatory neurotransmitter, in 50 mM Tris-acetate buffer (pH 7.4) at 30 degrees C in the absence of brain synaptic membranes resulted in a significant adsorption of the radioactivity to glass fiber filters routinely employed to trap the bound ligand in receptor binding assays. The adsorption was not only eliminated by the inclusion of L-isomers of structurally related amino acids, but also inhibited by that of most presumed agonists and antagonists for the brain glutamate receptors. This displaceable adsorption was a temperature-dependent nonreversible, and saturable phenomenon. Scatchard analysis of these data revealed that the adsorption consisted of a single component with an apparent dissociation constant of 73 nM. The displaceable adsorption was significantly attenuated by a concurrent incubation with papain, pronase E, and phospholipase C. A significant amount of the radioactivity was detected in the pass-through fraction of the Dowex column following an application of the reaction mixture incubated with purified [ 3 H]glutamate at 30 degree C for 60 min in the absence of membranous proteins added. Complete abolition of the displaceable adsorption resulted from the use of incubation buffer boiled at 100 degrees C as well as filtered through a nitrocellulose membrane filter with a pore size of 0.45 micron immediately before use. These results suggest that the displaceable adsorption may be attributable to the radioactive metabolite of [ 3 H]glutamate by microorganisms contaminating the Tris-acetate buffer. This might in part contribute to some of the controversial results with regard to receptor binding studies on acidic amino acids

  14. Pre-synaptic glycine GlyT1 transporter--NMDA receptor interaction: relevance to NMDA autoreceptor activation in the presence of Mg2+ ions.

    Science.gov (United States)

    Musante, Veronica; Summa, Maria; Cunha, Rodrigo A; Raiteri, Maurizio; Pittaluga, Anna

    2011-05-01

    Rat hippocampal glutamatergic terminals possess NMDA autoreceptors whose activation by low micromolar NMDA elicits glutamate exocytosis in the presence of physiological Mg(2+) (1.2 mM), the release of glutamate being significantly reduced when compared to that in Mg(2+)-free condition. Both glutamate and glycine were required to evoke glutamate exocytosis in 1.2 mM Mg(2+), while dizocilpine, cis-4-[phosphomethyl]-piperidine-2-carboxylic acid and 7-Cl-kynurenic acid prevented it, indicating that occupation of both agonist sites is needed for receptor activation. D-serine mimicked glycine but also inhibited the NMDA/glycine-induced release of [(3H]D-aspartate, thus behaving as a partial agonist. The NMDA/glycine-induced release in 1.2 mM Mg(2+) strictly depended on glycine uptake through the glycine transporter type 1 (GlyT1), because the GlyT1 blocker N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine hydrochloride, but not the GlyT2 blocker Org 25534, prevented it. Accordingly, [(3)H]glycine was taken up during superfusion, while lowering the external concentration of Na(+), the monovalent cation co-transported with glycine by GlyT1, abrogated the NMDA-induced effect. Western blot analysis of subsynaptic fractions confirms that GlyT1 and NMDA autoreceptors co-localize at the pre-synaptic level, where GluN3A subunits immunoreactivity was also recovered. It is proposed that GlyT1s coexist with NMDA autoreceptors on rat hippocampal glutamatergic terminals and that glycine taken up by GlyT1 may permit physiological activation of NMDA pre-synaptic autoreceptors. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  15. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica.

    Science.gov (United States)

    Kempsell, Andrew T; Fieber, Lynne A

    2015-01-01

    Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature vs. advanced age Aplysia californica (Aplysia). L-Glutamate- (L-Glu-) evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT) in sensory neurons (SN) isolated from mature but not aged animals. Activation of protein kinase A (PKA) and protein kinase C (PKC) signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems.

  16. Aspiration pneumonia in patients with cleft palate

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hun; Choi, Yo Won; Jeon, Seok Chol; Park, Choong Ki; Uhm, Ki Il [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2003-03-01

    To assess the incidence of aspiration pneumonia in infants with cleft palate and to compare the incidence between complete and incomplete types of cleft palate. A review of medical records revealed 100 infants who had undergone initial surgery to repair cleft palate in our hospital during a recent three-year period. Aspiration pneumonia was defined as the coexistence of pneumonia at chest radiography with a history of frequent choking during feeding. The anatomic distribution of aspiration pneumonia was analyzed, and the incidences of aspiration pneumonia in infants with complete and incomplete cleft palate were compared. Among 100 children, aspiration pneumonia was found in 35 (35%). Those with complete and incomplete cleft palate showed similar incidences of the condition (27 of 70 [39%] vs 8 of 30 [27%], p=0.36). Pneumonia was most commonly seen in the left lower lobe (11 of 35), followed by the right upper and lower lobes. Aspiration pneumonia is frequently associated with infants with cleft palate. There is no statistical difference in the incidence of aspiration pneumonia between the complete and the incomplete cleft palate group.

  17. Aspiration pneumonia in patients with cleft palate

    International Nuclear Information System (INIS)

    Lee, Seung Hun; Choi, Yo Won; Jeon, Seok Chol; Park, Choong Ki; Uhm, Ki Il

    2003-01-01

    To assess the incidence of aspiration pneumonia in infants with cleft palate and to compare the incidence between complete and incomplete types of cleft palate. A review of medical records revealed 100 infants who had undergone initial surgery to repair cleft palate in our hospital during a recent three-year period. Aspiration pneumonia was defined as the coexistence of pneumonia at chest radiography with a history of frequent choking during feeding. The anatomic distribution of aspiration pneumonia was analyzed, and the incidences of aspiration pneumonia in infants with complete and incomplete cleft palate were compared. Among 100 children, aspiration pneumonia was found in 35 (35%). Those with complete and incomplete cleft palate showed similar incidences of the condition (27 of 70 [39%] vs 8 of 30 [27%], p=0.36). Pneumonia was most commonly seen in the left lower lobe (11 of 35), followed by the right upper and lower lobes. Aspiration pneumonia is frequently associated with infants with cleft palate. There is no statistical difference in the incidence of aspiration pneumonia between the complete and the incomplete cleft palate group

  18. X-linked genes and risk of orofacial clefts

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Skare, Øivind; Lie, Rolv T

    2012-01-01

    Orofacial clefts are common birth defects of complex etiology, with an excess of males among babies with cleft lip and palate, and an excess of females among those with cleft palate only. Although genes on the X chromosome have been implicated in clefting, there has been no association analysis...

  19. Cadmium action in synapses in the brain

    International Nuclear Information System (INIS)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto

    2001-01-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of 109 CdCl 2 into the amygdala of rats, 109 Cd release into the extracellular space was facilitated by stimulation with high K + , suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 μM CdCl 2 . The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and γ-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  20. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases

    DEFF Research Database (Denmark)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura Frendrup

    2016-01-01

    to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes...... the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [15N]glutamate demonstrated activity of GDH......The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate–glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back...

  1. Early mother-child interaction and later quality of attachment in infants with an orofacial cleft compared to infants without cleft.

    Science.gov (United States)

    Habersaat, Stephanie; Monnier, Maryline; Peter, Camille; Bolomey, Luce; Borghini, Ayala; Despars, Josée; Pierrehumbert, Blaise; Müller-Nix, Carole; Ansermet, François; Hohlfeld, Judith

    2013-11-01

    Objective : The main objective of this study was to assess mother-child patterns of interaction in relation to later quality of attachment in a group of children with an orofacial cleft compared with children without cleft. Design : Families were contacted when the child was 2 months old for a direct assessment of mother-child interaction and then at 12 months for a direct assessment of the child's attachment. Data concerning socioeconomical information and posttraumatic stress symptoms in mothers were collected at the first appointment. Participants : Forty families of children with a cleft and 45 families of children without cleft were included in the study. Families were recruited at birth in the University Hospital of Lausanne. Results : Results showed that children with a cleft were more difficult and less cooperative during interaction at 2 months of age with their mother compared with children without a cleft. No significant differences were found in mothers or in dyadic interactive styles. Concerning the child's attachment at 12 months old, no differences were found in attachment security. However, secure children with a cleft were significantly more avoidant with their mother during the reunion episodes than secure children without cleft. Conclusion : Despite the facial disfigurement and the stress engendered by treatment during the first months of the infant's life, children with cleft and their mothers are doing as well as families without cleft with regard to the mothers' mental health, mother-child relationships, and later quality of attachment. A potential contribution for this absence of difference may be the pluridisciplinary support that families of children with cleft benefit from in Lausanne.

  2. Chapter 54: the discovery of neurotransmitters, and applications to neurology.

    Science.gov (United States)

    Sourkes, Theodore L

    2010-01-01

    The theory of chemical transmission has proved to be a powerful tool in the analysis of many aspects of neurological function, and its implications loom large on the horizon of neurology and psychiatry. Neurotransmitters are released at neuronal endings, diffuse rapidly across the synaptic cleft, and then act upon receptor proteins embedded in the membrane of the post-synaptic neuron or gland. Drugs are evaluated for their ability to stimulate or to block specific receptors, and in that way modify activity of the postsynaptic organ in order to achieve some desirable therapeutic effect. This chapter is concerned with our knowledge of some of the principal neurotransmitters, namely the primary amines: dopamine, noradrenaline, and serotonin; the quaternary amine: acetylcholine; and the aminoacids: gamma-aminobutyric acid, glutamic acid and glycine. The historical background to the discovery of these molecules as physiological neurotransmitters is presented, and their relation to various clinical states is discussed.

  3. The potential role of postsynaptic phospholipase C activity in synaptic facilitation and behavioral sensitization in Aplysia.

    Science.gov (United States)

    Fulton, Daniel; Condro, Michael C; Pearce, Kaycey; Glanzman, David L

    2008-07-01

    Previous findings indicate that synaptic facilitation, a cellular mechanism underlying sensitization of the siphon withdrawal response (SWR) in Aplysia, depends on a cascade of postsynaptic events, including activation of inositol triphosphate (IP3) receptors and release of Ca2+ from postsynaptic intracellular stores. These findings suggest that phospholipase C (PLC), the enzyme that catalyzes IP3 formation, may play an important role in postsynaptic signaling during facilitation and learning in Aplysia. Using the PLC inhibitor U73122, we found that PLC activity is required for synaptic facilitation following a 10-min treatment with 5-HT, as measured at 20 min after 5-HT washout. Prior work has indicated that facilitation at this time is supported primarily by postsynaptic processes. To determine whether postsynaptic PLC activity is involved in 5-HT-mediated facilitatory actions, we examined the effect of U73122 on enhancement of the response of motor neurons isolated in cell culture to glutamate, the sensory neuron transmitter. A 10-min application of 5-HT induced persistent (>40 min) enhancement of glutamate-evoked potentials (Glu-EPs) recorded from isolated motor neurons, and this enhancement was blocked by U73122. Finally, we showed that injecting U73122 into intact animals before behavioral training impaired intermediate-term sensitization, indicating that PLC activity contributes to this form of nonassociative learning.

  4. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B

    1996-01-01

    glutamate and sPLA2 from bee venom. sPLA2, at concentrations eliciting low neurotoxicity (acid into triacylglycerols. Free [3H]arachidonic acid accumulated at higher enzyme concentrations......, from Taipan snake venom. The NMDA receptor antagonist MK-801 blocked glutamate effects and partially inhibited sPLA2 OS2 but not sPLA2 from bee venom-induced arachidonic acid release. Thus, the synergy with glutamate and very low concentrations of exogenously added sPLA2 suggests a potential role......Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding...

  5. Parents' age and the risk of oral clefts

    DEFF Research Database (Denmark)

    Bille, C.; Skytthe, A.; Vach, W.

    2005-01-01

    BACKGROUND: Some malformations are clearly associated with older maternal age, but the effect of older age of the father is less certain. The aim of this study is to determine the degree to which maternal age and paternal age independently influence the risk of having a child with oral clefts....... In a joint analysis, both maternal and paternal ages were associated with the risk of cleft lip with or without cleft palate, but the contribution of each was dependent on the age of the other parent. In the analysis of cleft palate only, the effect of maternal age disappeared, leaving only paternal age...... as a risk factor. CONCLUSION: Both high maternal age and high paternal age were associated with cleft lip with or without cleft palate. Higher paternal age but not maternal age increased the risk of cleft palate only....

  6. Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

    Science.gov (United States)

    Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

    2016-01-15

    Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

  7. Congenital heart defects in children with oral clefts

    Directory of Open Access Journals (Sweden)

    Nahvi H.

    2007-09-01

    Full Text Available   Background: Oral clefts are among the most common congenital anomalies. Infants with oral clefts often have other associated congenital defects, especially congenital heart defects. The reported incidences and the types of associated malformations and congenital heart defects vary between different studies. The purpose of this study was to assess the incidence of associated congenital heart defects in children with oral clefts. Methods: All infants with cleft lip and palate referred to the Children's Medical Center and Bahramy; the teaching Hospitals of the Tehran University of Medical Sciences from 1991 to 2005 were prospectively enrolled in this study group. All patients were examined and noted by an academic cleft team contain; a pediatrician and a pediatric surgeon, and received cardiac consultation and echocardiography by a pediatric cardiologist. non cardiac associated anomalies, still born and patients without echocardiography were excluded from the study.  Data including age, gender, exposure to contagions and high risk elements ,consanguinity and familial history of oral cleft, type of oral cleft, results of cardiac consultation and echocardiography and associated cardiac anomalies were cumulated and analyzed by SSPS version 13.5Results: Among the 284 infants with oral clefts, 162 were male (57% and 122 were female (43%. Seventy-nine patients (27.8% had cleft lip, 84 (29.5% had cleft palate and 121 (42.6% had both cleft lip and palate. Of all the patients, 21.1% had congenital heart defects. the most common type Of these congenital heart defects(28.3%  was atrial septal defect.Conclusions: For patients with cleft lip and palate, we recommend preoperative cardiac consultation, careful examination and routine echocardiography for associated cardiac anomalies, as well as appropriate management and prophylactic antibiotic therapy for those with associated congenital heart anomaly.

  8. A perisynaptic ménage à trois between Dlg, DLin-7, and Metro controls proper organization of Drosophila synaptic junctions.

    Science.gov (United States)

    Bachmann, André; Kobler, Oliver; Kittel, Robert J; Wichmann, Carolin; Sierralta, Jimena; Sigrist, Stephan J; Gundelfinger, Eckart D; Knust, Elisabeth; Thomas, Ulrich

    2010-04-28

    Structural plasticity of synaptic junctions is a prerequisite to achieve and modulate connectivity within nervous systems, e.g., during learning and memory formation. It demands adequate backup systems that allow remodeling while retaining sufficient stability to prevent unwanted synaptic disintegration. The strength of submembranous scaffold complexes, which are fundamental to the architecture of synaptic junctions, likely constitutes a crucial determinant of synaptic stability. Postsynaptic density protein-95 (PSD-95)/ Discs-large (Dlg)-like membrane-associated guanylate kinases (DLG-MAGUKs) are principal scaffold proteins at both vertebrate and invertebrate synapses. At Drosophila larval glutamatergic neuromuscular junctions (NMJs) DlgA and DlgS97 exert pleiotropic functions, probably reflecting a few known and a number of yet-unknown binding partners. In this study we have identified Metro, a novel p55/MPP-like Drosophila MAGUK as a major binding partner of perisynaptic DlgS97 at larval NMJs. Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7. In a remarkably interdependent manner, Metro and DLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons. Using quantitative 3D-imaging we further demonstrate that the complex controls the size of postsynaptic glutamate receptor fields. Our findings accentuate the importance of perisynaptic scaffold complexes for synaptic stabilization and organization.

  9. Vesicular glutamate transporter-immunoreactivities in the vestibular nuclear complex of rat.

    Science.gov (United States)

    Deng, Jiao; Zhang, Fu-Xing; Pang, You-Wang; Li, Jin-Lian; Li, Yun-Qing

    2006-07-01

    Objective Aims to delineate the distribution profile of three isoforms of vesicular glutamate transporter (VGluT), viz. VGluT1-3, and their cellular localization within vestibular nuclear complex (VNC). Methods Brain sections from normal Sprague-Dawley rats were processed immunohistochemically for VGluT detection, employing avidin-biotinylated peroxidase complex method with 3-3'-diaminobenzidine (DAB) as chromogen. Results The whole VNC expressed all of the three transporters that were observed to be localized to the fiber endings. Compared with VGluT1 and VGluT3, VGluT2 demonstrated a relatively homogeneous distribution, with much higher density in VNC. VGluT3 displayed the highest density in lateral vestibular nucleus and group X, contrasting with the sparse immunostained puncta within vestibular medial and inferior nuclei. Conclusion Glutamtatergic pathways participate in the processing of vestibular signals within VNC mainly through the re-uptake of glutamate into synaptic vesicles by VGluT1 and 2, whereas VGluT3 may play a similar role mainly in areas other than medial and inferior nuclei of VNC.

  10. Vesicular glutamate transporter-immunoreactivities in the vestibular nuclear complex of rat

    Institute of Scientific and Technical Information of China (English)

    Jiao DENG; Fu-Xing ZHANG; You-Wang PANG; Jin-Lian LI; Yun-Qing LI

    2006-01-01

    Objective Aims to delineate the distribution profile of three isoforms of vesicular glutamate transporter (VGluT), viz. VGluT1~3, and their cellular localization within vestibular nuclear complex (VNC). Methods Brain sections from normal Sprague-Dawley rats were processed immunohistochemically for VGluT detection, employing avidinbiotinylated peroxidase complex method with 3-3'-diaminobenzidine (DAB) as chromogen. Results The whole VNC expressed all of the three transporters that were observed to be localized to the fiber endings. Compared with VGluT1 and VGluT3, VGluT2 demonstrated a relatively homogeneous distribution, with much higher density in VNC. VGluT3 displayed the highest density in lateral vestibular nucleus and group X, contrasting with the sparse immunostained puncta within vestibular medial and inferior nuclei. Conclusion Glutamtatergic pathways participate in the processing of vestibular signals within VNC mainly through the re-uptake of glutamate into synaptic vesicles by VGluT1 and 2, whereas VGluT3 may play a similar role mainly in areas other than medial and inferior nuclei of VNC.

  11. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

    DEFF Research Database (Denmark)

    Beaty, Terri H; Murray, Jeffrey C; Marazita, Mary L

    2010-01-01

    Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635...

  12. Hypertelorism and orofacial clefting revisited

    DEFF Research Database (Denmark)

    Weinberg, Seth M.; Leslie, Elizabeth J.; Hecht, Jacqueline T.

    2017-01-01

    Objective: Since the 1960s, multiple studies have reported a tendency toward hypertelorism in individuals with nonsyndromic orofacial clefts (OFCs). However, the association between specific cleft types and increased interorbital distance has been inconsistent. Using threedimensional (3D) surface...

  13. Cleft Lip and Palate Surgery

    Science.gov (United States)

    ... The experts in face, mouth and jaw surgery. Cleft Lip / Palate and Craniofacial Surgery This type of surgery is ... the carefully orchestrated, multiple-stage correctional program for cleft lip and palate patients. The goal is to help restore the ...

  14. Activation of β-adrenoceptor facilitates active avoidance learning through enhancement of glutamate levels in the hippocampal dentate gyrus.

    Science.gov (United States)

    Lv, Jing; Feng, Hao; Chen, Ling; Wang, Wei-Yao; Yue, Xue-Ling; Jin, Qing-Hua

    2017-10-18

    Long-term potentiation (LTP) is widely accepted as the best studied model for neurophysiological mechanisms that could underlie learning and memory formation. Despite a number of studies indicating that β-adrenoceptors in the hippocampal dentate gyrus (DG) is involved in the modulation of learning and memory as well as LTP, few studies have used glutamate release as a visual indicator in awake animals to explore the role of β-adrenoceptors in learning-dependent LTP. Therefore, in the present study, the effects of propranolol (an antagonist of β-adrenoceptor) and isoproterenol (an agonist of β-adrenoceptor) on extracellular concentrations of glutamate and amplitudes of field excitatory postsynaptic potential were measured in the DG region during active avoidance learning in freely moving conscious rats. In the control group, the glutamate level in the DG was significantly increased during the acquisition of active avoidance behavior and returned to basal level following extinction training. In propranolol group, antagonism of β-adrenoceptors in the DG significantly reduced the change in glutamate level, and the acquisition of the active avoidance behavior was significantly inhibited. In contrast, the change in glutamate level was significantly enhanced by isoproterenol, and the acquisition of the active avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in glutamate level were accompanied by corresponding changes in field excitatory postsynaptic potential amplitude and active avoidance behavior. Our results suggest that activation of β-adrenoceptors in the hippocampal DG facilitates active avoidance learning by modulations of glutamate level and synaptic efficiency in rats.

  15. Implementing the Brazilian Database on Orofacial Clefts

    Directory of Open Access Journals (Sweden)

    Isabella Lopes Monlleó

    2013-01-01

    Full Text Available Background. High-quality clinical and genetic descriptions are crucial to improve knowledge of orofacial clefts and support specific healthcare polices. The objective of this study is to discuss the potential and perspectives of the Brazilian Database on Orofacial Clefts. Methods. From 2008 to 2010, clinical and familial information on 370 subjects was collected by geneticists in eight different services. Data was centrally processed using an international system for case classification and coding. Results. Cleft lip with cleft palate amounted to 198 (53.5%, cleft palate to 99 (26.8%, and cleft lip to 73 (19.7% cases. Parental consanguinity was present in 5.7% and familial history of cleft was present in 26.3% subjects. Rate of associated major plus minor defects was 48% and syndromic cases amounted to 25% of the samples. Conclusions. Overall results corroborate the literature. Adopted tools are user friendly and could be incorporated into routine patient care. The BDOC exemplifies a network for clinical and genetic research. The data may be useful to develop and improve personalized treatment, family planning, and healthcare policies. This experience should be of interest for geneticists, laboratory-based researchers, and clinicians entrusted with OC worldwide.

  16. Maternal Risk Factors Associated with the Development of Cleft Lip and Cleft Palate in Mexico: A Case-Control Study.

    Science.gov (United States)

    Angulo-Castro, Emmanuel; Acosta-Alfaro, Luis F; Guadron-Llanos, Alma M; Canizalez-Román, Adrian; Gonzalez-Ibarra, Fernando; Osuna-Ramírez, Ignacio; Murillo-Llanes, Joel

    2017-07-01

    Cleft lip and palate, the most common developmental deformity, is seen worldwide and the etiology involves a combination of genetic and environmental factors. The purpose of this study was to determine the maternal risk factors associated with the development of cleft lip and cleft palate. We conducted a case control study at the Women's Hospital in Culiacan, Mexico. Medical records were analyzed, including patients who delivered babies with and without cleft lip and cleft palate from January 2010 to December 2015. Multiple variables were analyzed, including gestational age, weight at birth, the use of folic acid and multivitamins during pregnancy, smoking, alcohol abuse, the use of recreational drugs, history of sexually transmitted infections, marital status, socioeconomic status, education, and nutritional status. We found that the maternal risk factors with the strongest association for the development of cleft lip and cleft palate were the following: patients who were not taking folic acid during pregnancy [OR 3.27, 95% CI 1.32-8.09], P=0.00; patients who were not taking vitamin supplementation during pregnancy [OR 2.6, 95% CI 1.19-7.27], P=0.02; smoking during pregnancy [OR 2.05, 95% CI 1.23-3.41], P=0.01; and alcohol abuse during pregnancy [OR 1.90, 95% CI 1.17-3.08], P=0.03. The main risk factors associated with the development of cleft lip and cleft palate in a Mexican population at the Women's hospital in Culiacan, Sinaloa, Mexico were smoking, alcohol abuse, and patients not taking folic acid and multivitamins during pregnancy.

  17. Assessing Technical Performance and Determining the Learning Curve in Cleft Palate Surgery Using a High-Fidelity Cleft Palate Simulator.

    Science.gov (United States)

    Podolsky, Dale J; Fisher, David M; Wong Riff, Karen W; Szasz, Peter; Looi, Thomas; Drake, James M; Forrest, Christopher R

    2018-06-01

    This study assessed technical performance in cleft palate repair using a newly developed assessment tool and high-fidelity cleft palate simulator through a longitudinal simulation training exercise. Three residents performed five and one resident performed nine consecutive endoscopically recorded cleft palate repairs using a cleft palate simulator. Two fellows in pediatric plastic surgery and two expert cleft surgeons also performed recorded simulated repairs. The Cleft Palate Objective Structured Assessment of Technical Skill (CLOSATS) and end-product scales were developed to assess performance. Two blinded cleft surgeons assessed the recordings and the final repairs using the CLOSATS, end-product scale, and a previously developed global rating scale. The average procedure-specific (CLOSATS), global rating, and end-product scores increased logarithmically after each successive simulation session for the residents. Reliability of the CLOSATS (average item intraclass correlation coefficient (ICC), 0.85 ± 0.093) and global ratings (average item ICC, 0.91 ± 0.02) among the raters was high. Reliability of the end-product assessments was lower (average item ICC, 0.66 ± 0.15). Standard setting linear regression using an overall cutoff score of 7 of 10 corresponded to a pass score for the CLOSATS and the global score of 44 (maximum, 60) and 23 (maximum, 30), respectively. Using logarithmic best-fit curves, 6.3 simulation sessions are required to reach the minimum standard. A high-fidelity cleft palate simulator has been developed that improves technical performance in cleft palate repair. The simulator and technical assessment scores can be used to determine performance before operating on patients.

  18. Definition of critical periods for Hedgehog pathway antagonist-induced holoprosencephaly, cleft lip, and cleft palate.

    Directory of Open Access Journals (Sweden)

    Galen W Heyne

    Full Text Available The Hedgehog (Hh signaling pathway mediates multiple spatiotemporally-specific aspects of brain and face development. Genetic and chemical disruptions of the pathway are known to result in an array of structural malformations, including holoprosencephaly (HPE, clefts of the lip with or without cleft palate (CL/P, and clefts of the secondary palate only (CPO. Here, we examined patterns of dysmorphology caused by acute, stage-specific Hh signaling inhibition. Timed-pregnant wildtype C57BL/6J mice were administered a single dose of the potent pathway antagonist vismodegib at discrete time points between gestational day (GD 7.0 and 10.0, an interval approximately corresponding to the 15th to 24th days of human gestation. The resultant pattern of facial and brain dysmorphology was dependent upon stage of exposure. Insult between GD7.0 and GD8.25 resulted in HPE, with peak incidence following exposure at GD7.5. Unilateral clefts of the lip extending into the primary palate were also observed, with peak incidence following exposure at GD8.875. Insult between GD9.0 and GD10.0 resulted in CPO and forelimb abnormalities. We have previously demonstrated that Hh antagonist-induced cleft lip results from deficiency of the medial nasal process and show here that CPO is associated with reduced growth of the maxillary-derived palatal shelves. By defining the critical periods for the induction of HPE, CL/P, and CPO with fine temporal resolution, these results provide a mechanism by which Hh pathway disruption can result in "non-syndromic" orofacial clefting, or HPE with or without co-occurring clefts. This study also establishes a novel and tractable mouse model of human craniofacial malformations using a single dose of a commercially available and pathway-specific drug.

  19. Role of Na,K-ATPase α1 and α2 isoforms in the support of astrocyte glutamate uptake.

    Directory of Open Access Journals (Sweden)

    Nina B Illarionova

    Full Text Available Glutamate released during neuronal activity is cleared from the synaptic space via the astrocytic glutamate/Na(+ co-transporters. This transport is driven by the transmembrane Na(+ gradient mediated by Na,K-ATPase. Astrocytes express two isoforms of the catalytic Na,K-ATPase α subunits; the ubiquitously expressed α1 subunit and the α2 subunit that has a more specific expression profile. In the brain α2 is predominantly expressed in astrocytes. The isoforms differ with regard to Na+ affinity, which is lower for α2. The relative roles of the α1 and α2 isoforms in astrocytes are not well understood. Here we present evidence that the presence of the α2 isoform may contribute to a more efficient restoration of glutamate triggered increases in intracellular sodium concentration [Na(+]i. Studies were performed on primary astrocytes derived from E17 rat striatum expressing Na,K-ATPase α1 and α2 and the glutamate/Na(+ co-transporter GLAST. Selective inhibition of α2 resulted in a modest increase of [Na(+]i accompanied by a disproportionately large decrease in uptake of aspartate, an indicator of glutamate uptake. To compare the capacity of α1 and α2 to handle increases in [Na(+]i triggered by glutamate, primary astrocytes overexpressing either α1 or α2 were used. Exposure to glutamate 200 µM caused a significantly larger increase in [Na(+]i in α1 than in α2 overexpressing cells, and as a consequence restoration of [Na(+]i, after glutamate exposure was discontinued, took longer time in α1 than in α2 overexpressing cells. Both α1 and α2 interacted with astrocyte glutamate/Na(+ co-transporters via the 1st intracellular loop.

  20. Face facts: Genes, environment, and clefts

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J.C. [Univ. of Iowa, Iowa City IA (United States)

    1995-08-01

    Cleft lip and/or palate provides an ideal, albeit complex, model for the study of human developmental anomalies. Clefting disorders show a mix of well-defined syndromic causes (many with single-gene or environmental etiologies) coupled with their more common presentation in the nonsyndromic form. This summary presents some insight into the genetic causes of, etiology of and animal models for cleft lip and/or palate. 79 refs.

  1. Wavelet analysis of nonstationary fluctuations of Monte Carlo-simulated excitatory postsynaptic currents.

    Science.gov (United States)

    Aristizabal, F; Glavinovic, M I

    2003-10-01

    currents is not highly accurate owing to the varying number of the activatable AMPA channels caused by desensitization. The spatial nonuniformity of open, bound, and desensitized AMPA channels, and the time dependence and spatial nonuniformity of the glutamate concentration in the synaptic cleft, further reduce the accuracy of estimates of the number of AMPA channels from synaptic currents. In conclusion, wavelet analysis of nonstationary fluctuations of patch and synaptic currents expands our ability to determine accurately the variance and frequency of current fluctuations, demonstrates the limits of applicability of techniques currently used to evaluate the single channel current and number of AMPA channels, and offers new insights into the mechanisms involved in the generation of unitary quantal events at excitatory central synapses.

  2. Development and Evaluation of a Blog about Cleft Lip and Cleft Palate and Hearing.

    Science.gov (United States)

    Maximino, Luciana Paula; Zambonato, Ticiana Cristina de Freitas; Picolini-Pereira, Mirela Machado; Castro Corrêa, Camila de; Feniman, Mariza Ribeiro; Blasca, Wanderléia Quinhoneiro

    2018-01-01

    Introduction  Cleft lip and cleft palate can result in impairments in communication, specifically in hearing, making the use of technological resources such as blogs a fundamental guideline for health professionals. Objective  The aim of this study was to prepare and analyze the access to a blog about cleft lip and cleft palate and hearing as a pedagogical tool for health professionals. Methods  The first stage for the development of the blog was the selection of the content that would be addressed and the respective illustrations. The second stage was making the blog available through the WordPress platform, and the third stage included the evaluation of the blog, of the access to the WordPress statistical features, and of the quality of the blog through the Emory questionnaire, which was answered by 75 professionals. Results  The blog, titled "Fissure and Hearing", was developed with the architecture of a digital information environment containing a system of organization, navigation, labeling and search (first stage). The address hosting the blog was: http://fissuraeaudicao.wordpress.com (second stage). The result of the third stage included 56,269 views of the blog from different countries, and Brazil was the country with the highest viewing. Regarding the assessment by the Emory questionnaire, we found that for most of the major issues, the percentages obtained were or equal to 90%, while the analysis of the scales, navigation and structure presented the lowest scores. Conclusion  The blog was developed and enabled greater access to information available on the web about cleft lip and cleft palate and hearing.

  3. Treatment for Adults (with Cleft Lip and Palate)

    Science.gov (United States)

    ... here What treatment is available for adults with cleft lip and palate? Treatments currently available to infants and children with cleft lip and palate are also available to adults with clefts. Although ...

  4. Genetic determinants of facial clefting

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian

    2009-01-01

    BACKGROUND: Facial clefts are common birth defects with a strong genetic component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped in two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark...

  5. Asyndromic Bilateral Transverse Facial Cleft

    African Journals Online (AJOL)

    2013-04-23

    of this atypical cleft is unknown although the frequency ... on Tuesday, April 23, 2013, IP: 41.132.185.55] || Click here to download free Android application for this journal ... Facial cleft remains a source of social anxiety and in the past has lead ...

  6. Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting.

    Science.gov (United States)

    Howe, B J; Cooper, M E; Vieira, A R; Weinberg, S M; Resick, J M; Nidey, N L; Wehby, G L; Marazita, M L; Moreno Uribe, L M

    2015-07-01

    Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ(2) statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10(-8)) and permanent dentitions (51% vs. 8%, P = 4 × 10(-62)) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the

  7. Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

    Institute of Scientific and Technical Information of China (English)

    Hui Wang; Rui-Yun Peng

    2016-01-01

    With key roles in essential brain functions ranging from the long-term potentiation (LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor (NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca2+,postsynaptic density 95 (PSD-95),calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ),protein kinase A (PKA),mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.

  8. Ambulatory cleft lip surgery: A value analysis.

    Science.gov (United States)

    Arneja, Jugpal S; Mitton, Craig

    2013-01-01

    Socialized health systems face fiscal constraints due to a limited supply of resources and few reliable ways to control patient demand. Some form of prioritization must occur as to what services to offer and which programs to fund. A data-driven approach to decision making that incorporates outcomes, including safety and quality, in the setting of fiscal prudence is required. A value model championed by Michael Porter encompasses these parameters, in which value is defined as outcomes divided by cost. To assess ambulatory cleft lip surgery from a quality and safety perspective, and to assess the costs associated with ambulatory cleft lip surgery in North America. Conclusions will be drawn as to how the overall value of cleft lip surgery may be enhanced. A value analysis of published articles related to ambulatory cleft lip repair over the past 30 years was performed to determine what percentage of patients would be candidates for ambulatory cleft lip repair from a quality and safety perspective. An economic model was constructed based on costs associated with the inpatient stay related to cleft lip repair. On analysis of the published reports in the literature, a minority (28%) of patients are currently discharged in an ambulatory fashion following cleft lip repair. Further analysis suggests that 88.9% of patients would be safe candidates for same-day discharge. From an economic perspective, the mean cost per patient for the overnight admission component of ambulatory cleft surgery to the health care system in the United States was USD$2,390 and $1,800 in Canada. The present analysis reviewed germane publications over a 30-year period, ultimately suggesting that ambulatory cleft lip surgery results in preservation of quality and safety metrics for most patients. The financial model illustrates a potential cost saving through the adoption of such a practice change. For appropriately selected patients, ambulatory cleft surgery enhances overall health care value.

  9. Economic Valuation of the Global Burden of Cleft Disease Averted by a Large Cleft Charity.

    Science.gov (United States)

    Poenaru, Dan; Lin, Dan; Corlew, Scott

    2016-05-01

    This study attempts to quantify the burden of disease averted through the global surgical work of a large cleft charity, and estimate the economic impact of this effort over a 10-year period. Anonymized data of all primary cleft lip and cleft palate procedures in the Smile Train database were analyzed and disability-adjusted life years (DALYs) calculated using country-specific life expectancy tables, established disability weights, and estimated success of surgery and residual disability probabilities; multiple age weighting and discounting permutations were included. Averted DALYs were calculated and gross national income (GNI) per capita was then multiplied by averted DALYs to estimate economic gains. 548,147 primary cleft procedures were performed in 83 countries between 2001 and 2011. 547,769 records contained complete data available for the study; 58 % were cleft lip and 42 % cleft palate. Averted DALYs ranged between 1.46 and 4.95 M. The mean economic impact ranged between USD 5510 and 50,634 per person. This corresponded to a global economic impact of between USD 3.0B and 27.7B USD, depending on the DALY and GNI values used. The estimated cost of providing these procedures based on an average reimbursement rate was USD 197M (0.7-6.6 % of the estimated impact). The immense economic gain realized through procedures focused on a small proportion of the surgical burden of disease highlights the importance and cost-effectiveness of surgical treatment globally. This methodology can be applied to evaluate interventions for other conditions, and for evidence-based health care resource allocation.

  10. Presurgical Unilateral Cleft Lip Anthropometrics and the Presence of Dental Anomalies.

    Science.gov (United States)

    Antonarakis, Gregory S; Fisher, David M

    2015-07-01

    To investigate associations between cleft lip anthropometrics and dental anomalies in the permanent dentition in unilateral cleft lip patients. Retrospective cross-sectional study. Children with unilateral clefts of the lip, with or without cleft palate. Anthropometric lip measurements, made immediately prior to lip repair, were available for each patient. The presence of dental anomalies in the permanent dentition was assessed radiographically. The presence of associations between anthropometric lip measurements and prevalence rates of different dental anomalies were determined using logistic regression analyses. In the 122 included patients, the cleft lateral lip element was deficient in height in 80% and in transverse length in 84% of patients. Patients with more deficient cleft side lateral lip height and less deficient cleft side lateral lip transverse length were more likely to present with cleft side maxillary lateral incisor agenesis. On the other hand, patients with a less deficient cleft side lateral lip height and more deficient cleft side lateral lip transverse length were more likely to present with a cleft side supernumerary maxillary lateral incisor. When looking only at incomplete clefts, the cleft side lateral lip transverse length deficiency was more predictive of the presence of supernumerary maxillary lateral incisors (P = .030), while for complete clefts, the cleft side lateral lip height deficiency was more predictive of the presence of maxillary lateral incisor agenesis (P = .035). In patients with unilateral clefts, cleft lip anthropometrics have a predictive role in determining the occurrence of dental anomalies.

  11. The Prevalence of Cleft Lip and Cleft Palate and Related Risk Factors among Iranian Children from 2000 to 2016: a Literature Review

    Directory of Open Access Journals (Sweden)

    Arman Jafari

    2017-04-01

    Full Text Available BackgroundCleft lip and cleft palate (also, known as or facial clefts, are amongst the most common congenital deformities affecting the jaw and face as well as the most common defects associated with lip and palate. Thus, the current study was an attempt to investigate the prevalence and risk factors of or facial clefts in Iranian children.Materials and Methods:The present study, was conducted through a systematic search for articles recorded in the internal database (SID, IranMedex and Magiran, and external authoritative databases (Google scholar, PubMed, Science Direct, MEDLINE, CINAHL and EMBASE using the keywords including "cleft lip", "Iranian", "cleft palate", and "children" from 2000 to 2016. Then, 61 articles were collected. 47 studies with associated incidence or prevalence of cleft lip and cleft palate were included.Results:According to the findings of the review of the studies conducted in Iran, it is revealed that the prevalence of cleft lip and cleft palate was from 0.78 to 2.14 in Iranian children. It was revealed that several factors contributing to the development of this disorder consist of Family history ( P< 0.001, Antibiotics, ( P< 0.001, Stress in the first trimester of pregnancy (P=0.048, BMI before pregnancy (P=0.036 Seasonal factors (P= 0.03, and Consanguineous marriage (P=0.02.ConclusionAccording to the results of the present study, the prevalence of cleft lip and cleft palate is high in Iran in comparison with international studies. Furthermore, the prevalence of this disorder is reported to be higher in males than females. Therefore, it is recommended arrange the practical programs in order to help parents eliminate or diminish the factors that affect the prevalence of this disorder and complications.

  12. Evidence-based medicine: cleft palate.

    Science.gov (United States)

    Chepla, Kyle J; Gosain, Arun K

    2013-12-01

    After reading this article, the participant should be able to: 1. Describe recent changes in treatment of cleft palate. 2. Compare the efficacy of different surgical treatments. 3. Assess their own knowledge of cleft palate repair. 4. Determine where further individual in-depth study and development are warranted. The Maintenance of Certification in Plastic Surgery series is designed to ensure professional development and measure continued competency within a specialty or subspecialty. The present article provides an evaluation of the interval studies regarding the management of cleft palate with a specific focus on craniofacial growth, speech outcomes, and obstructive sleep apnea since the last Maintenance of Certification in Plastic Surgery article on the subject published in 2010. This purpose of this article is to update plastic and craniomaxillofacial surgeons on recent changes in treatment of cleft palate, provide a means for accurate self-assessment, and guide further individual in-depth study and development.

  13. Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice

    Science.gov (United States)

    Hunt, Robert F.; Scheff, Stephen W.; Smith, Bret N.

    2011-01-01

    Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury, versus those from control or contralateral slices. Further, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus. PMID:21543618

  14. Branchial cleft cyst

    Directory of Open Access Journals (Sweden)

    Vaishali Nahata

    2016-01-01

    Full Text Available Branchial cleft cyst, sinuses, and fistulae are among the most commonly encountered congenital anomalies in pediatric otolaryngic practice. They can present difficulty in diagnosis and surgical management. Here, I report a case of 14-year-old boy who presented with asymptomatic, congenital swelling located just below the jawline in the lateral part of the neck. The lesion was excised surgically. Histopathology showed the cyst lined by squamous as well as columnar ciliated epithelium, which was a characteristic finding of branchial cleft cyst. The aim of presenting this case is its rarity.

  15. Branchial Cleft Cyst

    Science.gov (United States)

    Nahata, Vaishali

    2016-01-01

    Branchial cleft cyst, sinuses, and fistulae are among the most commonly encountered congenital anomalies in pediatric otolaryngic practice. They can present difficulty in diagnosis and surgical management. Here, I report a case of 14-year-old boy who presented with asymptomatic, congenital swelling located just below the jawline in the lateral part of the neck. The lesion was excised surgically. Histopathology showed the cyst lined by squamous as well as columnar ciliated epithelium, which was a characteristic finding of branchial cleft cyst. The aim of presenting this case is its rarity. PMID:27904209

  16. Branchial Cleft Cyst.

    Science.gov (United States)

    Nahata, Vaishali

    2016-01-01

    Branchial cleft cyst, sinuses, and fistulae are among the most commonly encountered congenital anomalies in pediatric otolaryngic practice. They can present difficulty in diagnosis and surgical management. Here, I report a case of 14-year-old boy who presented with asymptomatic, congenital swelling located just below the jawline in the lateral part of the neck. The lesion was excised surgically. Histopathology showed the cyst lined by squamous as well as columnar ciliated epithelium, which was a characteristic finding of branchial cleft cyst. The aim of presenting this case is its rarity.

  17. Unusual extension of the first branchial cleft anomaly.

    Science.gov (United States)

    Ada, Mehmet; Korkut, Nazim; Güvenç, M Güven; Acioğlu, Engin; Yilmaz, Süleyman; Cevikbaş, Uğur

    2006-03-01

    First branchial cleft is the only branchial structure that persists as the external ear canal, while all other clefts are resorbed. Incomplete obliteration and the degree of closure cause the varied types of first branchial cleft anomalies. They were classified based on the anatomical and histological features. We present an unusual type of first branchial cleft anomaly involving the external auditory canal, the middle ear and the nasopharynx through the eustachian tube.

  18. Role of synaptic structural plasticity in impairments of spatial learning and memory induced by developmental lead exposure in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Yongmei Xiao

    Full Text Available Lead (Pb is found to impair cognitive function. Synaptic structural plasticity is considered to be the physiological basis of synaptic functional plasticity and has been recently found to play important roles in learning and memory. To study the effect of Pb on spatial learning and memory at different developmental stages, and its relationship with alterations of synaptic structural plasticity, postnatal rats were randomly divided into three groups: Control; Pre-weaning Pb (Parents were exposed to 2 mM PbCl2 3 weeks before mating until weaning of pups; Post-weaning Pb (Weaned pups were exposed to 2 mM PbCl2 for 9 weeks. The spatial learning and memory of rats was measured by Morris water maze (MWM on PND 85-90. Rat pups in Pre-weaning Pb and Post-weaning Pb groups performed significantly worse than those in Control group (p<0.05. However, there was no significant difference in the performance of MWM between the two Pb-exposure groups. Before MWM (PND 84, the number of neurons and synapses significantly decreased in Pre-weaning Pb group, but not in Post-weaning Pb group. After MWM (PND 91, the number of synapses in Pre-weaning Pb group increased significantly, but it was still less than that of Control group (p<0.05; the number of synapses in Post-weaning Pb group was also less than that of Control group (p<0.05, although the number of synapses has no differences between Post-weaning Pb and Control groups before MWM. In both Pre-weaning Pb and Post-weaning Pb groups, synaptic structural parameters such as thickness of postsynaptic density (PSD, length of synaptic active zone and synaptic curvature increased significantly while width of synaptic cleft decreased significantly compared to Control group (p<0.05. Our data demonstrated that both early and late developmental Pb exposure impaired spatial learning and memory as well as synaptic structural plasticity in Wistar rats.

  19. Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of [3H]dopamine from striatal slices

    International Nuclear Information System (INIS)

    Bowyer, J.F.; Scallet, A.C.; Holson, R.R.; Lipe, G.W.; Slikker, W. Jr.; Ali, S.F.

    1991-01-01

    The interactions of MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine], glutamate and glutamine with methamphetamine (METH)-evoked release of [ 3 H]dopamine were assessed in vitro to determine whether MK-801 inhibition of METH neurotoxicity might be mediated presynaptically, and to evaluate the effects of glutamatergic stimulation on METH-evoked dopamine release. MK-801 inhibition of glutamate- or METH-evoked dopamine release might reduce synaptic dopamine levels during METH exposure and decrease the formation of 6-hydroxydopamine or other related neurotoxins. Without Mg 2+ present, 40 microM and 1 mM glutamate evoked a N-methyl-D-aspartate receptor-mediated [ 3 H]dopamine and [ 3 H]metabolite (tritium) release of 3 to 6 and 12 to 16% of total tritium stores, respectively, from striatal slices. With 1.50 mM Mg 2+ present, 10 mM glutamate alone or in combination with the dopamine uptake blocker nomifensine released only 2.1 or 4.2%, respectively, of total tritium stores, and release was only partially dependent on N-methyl-D-aspartate-type glutamate receptors. With or without 1.50 mM Mg 2+ present, 0.5 or 5 microM METH evoked a substantial release of tritium (5-8 or 12-21% of total stores, respectively). METH-evoked dopamine release was not affected by 5 microM MK-801 but METH-evoked release was additive with glutamate-evoked release. Without Mg 2+ present, 1 mM glutamine increased glutamate release and induced the release of [ 3 H]dopamine and metabolites. Both 0.5 and 5 microM METH also increased tritium release with 1 mM glutamine present. When striatal slices were exposed to 5 microM METH this glutamine-evoked release of glutamate was increased more than 50%

  20. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

    Directory of Open Access Journals (Sweden)

    Laura Musazzi

    2010-01-01

    Full Text Available Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated, and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486. On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats. Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress

  1. Rescue of Synaptic Phenotypes and Spatial Memory in Young Fragile X Mice.

    Science.gov (United States)

    Sun, Miao-Kun; Hongpaisan, Jarin; Alkon, Daniel L

    2016-05-01

    Fragile X syndrome (FXS) is characterized by synaptic immaturity, cognitive impairment, and behavioral changes. The disorder is caused by transcriptional shutdown in neurons of thefragile X mental retardation 1gene product, fragile X mental retardation protein. Fragile X mental retardation protein is a repressor of dendritic mRNA translation and its silencing leads to dysregulation of synaptically driven protein synthesis and impairments of intellect, cognition, and behavior, and FXS is a disorder that currently has no effective therapeutics. Here, young fragile X mice were treated with chronic bryostatin-1, a relatively selective protein kinase Cεactivator, which induces synaptogenesis and synaptic maturation/repair. Chronic treatment with bryostatin-1 rescues young fragile X mice from the disorder phenotypes, including normalization of most FXS abnormalities in 1) hippocampal brain-derived neurotrophic factor expression, 2) postsynaptic density-95 levels, 3) transformation of immature dendritic spines to mature synapses, 4) densities of the presynaptic and postsynaptic membranes, and 5) spatial learning and memory. The therapeutic effects were achieved without downregulation of metabotropic glutamate receptor (mGluR) 5 in the hippocampus and are more dramatic than those of a late-onset treatment in adult fragile X mice. mGluR5 expression was in fact lower in fragile X mice and its expression was restored with the bryostatin-1 treatment. Our results show that synaptic and cognitive function of young FXS mice can be normalized through pharmacological treatment without downregulation of mGluR5 and that bryostatin-1-like agents may represent a novel class of drugs to treat fragile X mental retardation at a young age and in adults. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  2. The Cleft Aesthetic Rating Scale for 18-Year-Old Unilateral Cleft Lip and Palate Patients: A Tool for Nasolabial Aesthetics Assessment.

    Science.gov (United States)

    Mulder, F J; Mosmuller, D G M; de Vet, H C W; Mouës, C M; Breugem, C C; van der Molen, A B Mink; Don Griot, J P W

    2018-01-01

    Objective To develop a reliable and easy-to-use method to assess the nasolabial appearance of 18-year-old patients with unilateral cleft lip and palate (CLP). Design Retrospective analysis of nasolabial aesthetics using a 5-point ordinal scale and newly developed photographic reference scale: the Cleft Aesthetic Rating Scale (CARS). Three cleft surgeons and 20 medical students scored the nasolabial appearance on standardized frontal photographs. Setting VU University Medical Center, Amsterdam. Patients Inclusion criteria: 18-year-old patients, unilateral cleft lip and palate, available photograph of the frontal view. history of facial trauma, congenital syndromes affecting facial appearance. Eighty photographs were available for scoring. Main Outcome Measures The interobserver and intraobserver reliability of the CARS for 18-year-old patients when used by cleft surgeons and medical students. Results The interobserver reliability for the nose and lip together was 0.64 for the cleft surgeons and 0.61 for the medical students. There was an intraobserver reliability of 0.75 and 0.78 from the surgeons and students, respectively, on the nose and lip together. No significant difference was found between the cleft surgeons and medical students in the way they scored the nose ( P = 0.22) and lip ( P = 0.72). Conclusions The Cleft Aesthetic Rating Scale for 18-year-old patients has a substantial overall estimated reliability when the average score is taken from three or more cleft surgeons or medical students assessing the nasolabial aesthetics of CLP patients.

  3. Cleft lip and palate surgery in children: Anaesthetic considerations ...

    African Journals Online (AJOL)

    Background: The Care of cleft patients is very challenging. Team cleft care is usually lacking in many developing countries due to shortage of qualified manpower. This study is aimed at highlighting anaesthetic challenges in the management of cleft in children. Patients and Methods: This was a study of cleft lip and palate ...

  4. Comparing caries risk profiles between 5- and 10- year-old children with cleft lip and/or palate and non-cleft controls

    DEFF Research Database (Denmark)

    Sundell, Anna Lena; Ullbro, Christer; Marcusson, Agneta

    2015-01-01

    of cleft lip and/or palate (CL(P)) children with non-cleft controls in the same age using a computerized caries risk assessment model. METHODS: The study group consisted of 133 children with CL(P) (77 subjects aged 5 years and 56 aged 10 years) and 297 non-cleft controls (133 aged 5 years and 164 aged 10......BACKGROUND: Previous studies have suggested that children with oral clefts may have higher caries prevalence in comparison with non-cleft controls but the relative importance of the potential risk factors is not clear. The aim of this study was to compare the caries risk profiles in a group...

  5. Teaching Palatoplasty Using a High-Fidelity Cleft Palate Simulator.

    Science.gov (United States)

    Cheng, Homan; Podolsky, Dale J; Fisher, David M; Wong, Karen W; Lorenz, H Peter; Khosla, Rohit K; Drake, James M; Forrest, Christopher R

    2018-01-01

    Cleft palate repair is a challenging procedure for cleft surgeons to teach. A novel high-fidelity cleft palate simulator has been described for surgeon training. This study evaluates the simulator's effect on surgeon procedural confidence and palatoplasty knowledge among learners. Plastic surgery trainees attended a palatoplasty workshop consisting of a didactic session on cleft palate anatomy and repair followed by a simulation session. Participants completed a procedural confidence questionnaire and palatoplasty knowledge test immediately before and after the workshop. All participants reported significantly higher procedural confidence following the workshop (p cleft palate surgery experience had higher procedural confidence before (p cleft palate experience did not have higher mean baseline test scores than those with no experience (30 percent versus 28 percent; p > 0.05), but did have significantly higher scores after the workshop (61 percent versus 35 percent; p cleft palate simulator as a training tool to teach palatoplasty. Improved procedural confidence and knowledge were observed after a single session, with benefits seen among trainees both with and without previous cleft experience.

  6. Isolated cleft of the ala nasi: A report of seven cases

    Directory of Open Access Journals (Sweden)

    J Rajesh Jinka

    2012-01-01

    Full Text Available Craniofacial clefts other than cleft lip & palate are reported to be 1.4 to 4.9 per 100,000 live births. Of these, clefts of nose are usually associated with other clefts. Isolated cleft of Ala is rare, 0.7% of all clefts reported by Monasterio. In an analysis of photographic records of 3,500 consecutive patients with craniofacial clefts including cleft lip & palate registered with us between 1985- 2012 which were accessed through our data base, 13 patients with nasal clefts were identified, seven out of which had Isolated cleft of the Ala. All were treated by a rotation flap of the Ala with good results with the longest follow up of 14Yrs. The authors have emphasised the rarity of the condition and presented a simple surgical procedure for correction. In the opinion of the authors this very simple procedure which can be performed by the junior surgeon gives a good long term result in the management of cleft Ala.

  7. Bilateral optic disc pit with maculopathy in a patient with cleft lip and cleft palate

    Directory of Open Access Journals (Sweden)

    Anisha Seth

    2015-01-01

    Full Text Available Optic disc pit (ODP is small, gray-white, oval depression found at the optic nerve head. It is a congenital defect that occurs due to imperfect closure of superior edge of the embryonic fissure. Cleft lip and palate are also congenital midline abnormalities occurring due to defect in the fusion of frontonasal prominence, maxillary prominence and mandibular prominence. There is only one case report describing the occurrence of ODP in a young patient with cleft lip and palate who also had basal encephalocele. We describe a 52-year-old patient with congenital cleft lip and palate with bilateral ODP with maculopathy but without any other midline abnormality.

  8. An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers.

    Science.gov (United States)

    Linhoff, Michael W; Laurén, Juha; Cassidy, Robert M; Dobie, Frederick A; Takahashi, Hideto; Nygaard, Haakon B; Airaksinen, Matti S; Strittmatter, Stephen M; Craig, Ann Marie

    2009-03-12

    Delineating the molecular basis of synapse development is crucial for understanding brain function. Cocultures of neurons with transfected fibroblasts have demonstrated the synapse-promoting activity of candidate molecules. Here, we performed an unbiased expression screen for synaptogenic proteins in the coculture assay using custom-made cDNA libraries. Reisolation of NGL-3/LRRC4B and neuroligin-2 accounts for a minority of positive clones, indicating that current understanding of mammalian synaptogenic proteins is incomplete. We identify LRRTM1 as a transmembrane protein that induces presynaptic differentiation in contacting axons. All four LRRTM family members exhibit synaptogenic activity, LRRTMs localize to excitatory synapses, and artificially induced clustering of LRRTMs mediates postsynaptic differentiation. We generate LRRTM1(-/-) mice and reveal altered distribution of the vesicular glutamate transporter VGLUT1, confirming an in vivo synaptic function. These results suggest a prevalence of LRR domain proteins in trans-synaptic signaling and provide a cellular basis for the reported linkage of LRRTM1 to handedness and schizophrenia.

  9. NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition

    Directory of Open Access Journals (Sweden)

    María Verónica Baez

    2018-01-01

    Full Text Available NMDA ionotropic glutamate receptors (NMDARs are crucial in activity-dependent synaptic changes and in learning and memory. NMDARs are composed of two GluN1 essential subunits and two regulatory subunits which define their pharmacological and physiological profile. In CNS structures involved in cognitive functions as the hippocampus and prefrontal cortex, GluN2A and GluN2B are major regulatory subunits; their expression is dynamic and tightly regulated, but little is known about specific changes after plasticity induction or memory acquisition. Data strongly suggest that following appropriate stimulation, there is a rapid increase in surface GluN2A-NMDAR at the postsynapses, attributed to lateral receptor mobilization from adjacent locations. Whenever synaptic plasticity is induced or memory is consolidated, more GluN2A-NMDARs are assembled likely using GluN2A from a local translation and GluN1 from local ER. Later on, NMDARs are mobilized from other pools, and there are de novo syntheses at the neuron soma. Changes in GluN1 or NMDAR levels induced by synaptic plasticity and by spatial memory formation seem to occur in different waves of NMDAR transport/expression/degradation, with a net increase at the postsynaptic side and a rise in expression at both the spine and neuronal soma. This review aims to put together that information and the proposed hypotheses.

  10. Evidence for presynaptically silent synapses in the immature hippocampus

    International Nuclear Information System (INIS)

    Yoon, Jae Young; Choi, Sukwoo

    2017-01-01

    Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses. Glutamate transients predicted based on the two presynaptic mechanisms have been shown to activate only high-affinity NMDARs, but not low-affinity AMPARs. Interestingly, a previous study has developed a new approach to distinguish between the two presynaptic mechanisms using dextran, an inert macromolecule that reduces the diffusivity of released glutamate: postsynaptic responses through the fusion pore mechanism, but not through the spillover mechanism, are potentiated by reduced glutamate diffusivity. Therefore, we reasoned that if the fusion pore mechanism underlies silent synapses, dextran application would reveal AMPAR-mediated synaptic responses at silent synapses. In the present study, we recorded AMPAR-mediated synaptic responses at the CA3-CA1 synapses in neonatal rats in the presence of blockers for NMDARs and GABAARs. Bath application of dextran revealed synaptic responses at silent synapses. GYKI53655, a selective AMPAR-antagonist, completely inhibited the unsilenced synaptic responses, indicating that the unsilenced synaptic responses are mediated by AMPARs. The dextran-mediated reduction in glutamate diffusivity would also lead to the activation of metabotropic glutamate receptors (mGluRs), which might induce unsilencing via the activation of unknown intracellular signaling. Hence, we determined whether mGluR-blockers alter

  11. Midline nasal dermoid cyst with Tessier's 0 cleft

    OpenAIRE

    Guruprasad, Yadavalli; Chauhan, Dinesh Singh

    2014-01-01

    This is a rare anomaly of midline nasal dermoid cyst (NDC) along with Tessier's 0 cleft. Midline NDCs present most commonly result from aberrant embryological development, and most commonly give rise to bifid nasal deformity resulting in midline cleft of the nose. Craniofacial clefts are among the most disfiguring of all facial anomalies. They exist in a multitude of patterns and with varying degrees of severity. The bifid nose deformity is generally an indicator of Tessier number 0 cleft. We...

  12. Assessment of scar quality after cleft lip closure

    NARCIS (Netherlands)

    Frans, Franceline A.; van Zuijlen, Paul P. M.; Griot, J. P. W. Don; van der Horst, Chantal M. A. M.

    2012-01-01

    To assess scar quality after cleft lip repair. The linear scars of patients with cleft lip with or without cleft palate were evaluated in a prospective study using the Patient and Observer Scar Assessment Scale. Linear regression was performed to identify which scar characteristics were important

  13. Assessing Angle's malocclusion among cleft lip and/or palate patients in Jammu.

    Science.gov (United States)

    Gupta, Akshay; Gupta, Anur; Bhardwaj, Amit; Vikram, S; Gomathi, Ajeetha; Singh, Karanprakash

    2016-04-01

    The study was conducted to examine the patients with abnormalities of cleft lip and/or palate and its association with different types of malocclusion. This descriptive study was done among 168 patients with abnormalities of cleft lip and/or palate. Angle's classification of malocclusion was applied for assessment of occlusion as Class I, Class II, and Class III. The types of oral clefts classification such as cleft lip unilateral and cleft lip bilateral, cleft palate (CP), unilateral cleft lip with palate (UCLP) and bilateral cleft lip with palate (BCLP) was considered. Chi-square test was applied to analyze the data at P clefts patients as cleft lip (81), CP (31), and both cleft lip and palate (53). The occurrence of unilateral cleft lip (44) was maximum among the sample followed by UCLP (39), and bilateral cleft lip (31). Maximum subjects with Class II (10.7%) and Class III (4.9%) malocclusion were seen with unilateral cleft lip deformities. None of the patients with UCLP had Class III malocclusion. Cleft lip was the most commonly observed deformity and high frequency of Class II and III malocclusion was evident. Therefore, patients with such abnormalities should be screened timely.

  14. Cleft palate caused by congenital teratoma.

    Science.gov (United States)

    Veyssière, Alexis; Streit, Libor; Traoré, Hamady; Bénateau, Hervé

    2017-02-01

    A cleft palate results from incomplete fusion of the lateral palatine processes, the median nasal septum and the median palatine process. This case report describes a rare case of congenital teratoma originating from the nasal septum that may have interfered with the fusion of the palatal shelves during embryonic development, resulting in a cleft palate. An infant girl was born at 40 weeks of gestation weighing 3020 g with a complete cleft palate associated with a large central nasopharyngeal tumour. Computed tomography (CT) of the head showed a well defined mass of mixed density. The tumour was attached to the nasal septum in direct contact with the cleft palate. A biopsy confirmed the teratoma. Tumour resection was performed at 5 months, soft palate reconstruction at 7 months and hard palate closure at 14 months. There was no sign of local recurrence 1 year later. Most teratomas are benign and the prognosis is usually good. However, recurrence is not rare if germ cell carcinomatous foci are present within the teratoma. For these reasons, we advocate the use of a two-stage procedure in which closure of the cleft palate is postponed until histological examination confirms complete excision of the teratoma.

  15. Laryngo-tracheo-oesophageal clefts

    Directory of Open Access Journals (Sweden)

    Leboulanger Nicolas

    2011-12-01

    Full Text Available Abstract A laryngo-tracheo-esophageal cleft (LC is a congenital malformation characterized by an abnormal, posterior, sagittal communication between the larynx and the pharynx, possibly extending downward between the trachea and the esophagus. The estimated annual incidence of LC is 1/10,000 to 1/20,000 live births, accounting for 0.2% to 1.5% of congenital malformations of the larynx. These incidence rates may however be underestimated due to difficulty in diagnosing minor forms and a high mortality rate in severe forms. A slightly higher incidence has been reported in boys than in girls. No specific geographic distribution has been found. Depending on the severity of the malformation, patients may present with stridor, hoarse cry, swallowing difficulties, aspirations, cough, dyspnea and cyanosis through to early respiratory distress. Five types of laryngo-tracheo-esophageal cleft have been described based on the downward extension of the cleft, which typically correlates with the severity of symptoms: Type 0 laryngo-tracheo-esophageal cleft to Type 4 laryngo-tracheo-esophageal cleft. LC is often associated with other congenital abnormalities/anomalies (16% to 68%, mainly involving the gastro-intestinal tract, which include laryngomalacia, tracheo-bronchial dyskinesia, tracheo-bronchomalacia (mostly in types 3 and 4, and gastro-esophageal reflux disease (GERD. The syndromes most frequently associated with an LC are Opitz/BBB syndrome, Pallister Hall syndrome, VACTERL/VATER association, and CHARGE syndrome. Laryngeal clefts result from failure of fusion of the posterior cricoid lamina and abnormal development of the tracheo-esophageal septum. The causes of the embryological developmental anomalies leading to LC are not known but are thought to be multifactorial. LC appears to be mostly sporadic although some familial cases with suspected autosomal dominant transmission have been reported. The age of diagnosis depends mainly on the severity of

  16. Laryngo-tracheo-oesophageal clefts

    Science.gov (United States)

    2011-01-01

    A laryngo-tracheo-esophageal cleft (LC) is a congenital malformation characterized by an abnormal, posterior, sagittal communication between the larynx and the pharynx, possibly extending downward between the trachea and the esophagus. The estimated annual incidence of LC is 1/10,000 to 1/20,000 live births, accounting for 0.2% to 1.5% of congenital malformations of the larynx. These incidence rates may however be underestimated due to difficulty in diagnosing minor forms and a high mortality rate in severe forms. A slightly higher incidence has been reported in boys than in girls. No specific geographic distribution has been found. Depending on the severity of the malformation, patients may present with stridor, hoarse cry, swallowing difficulties, aspirations, cough, dyspnea and cyanosis through to early respiratory distress. Five types of laryngo-tracheo-esophageal cleft have been described based on the downward extension of the cleft, which typically correlates with the severity of symptoms: Type 0 laryngo-tracheo-esophageal cleft to Type 4 laryngo-tracheo-esophageal cleft. LC is often associated with other congenital abnormalities/anomalies (16% to 68%), mainly involving the gastro-intestinal tract, which include laryngomalacia, tracheo-bronchial dyskinesia, tracheo-bronchomalacia (mostly in types 3 and 4), and gastro-esophageal reflux disease (GERD). The syndromes most frequently associated with an LC are Opitz/BBB syndrome, Pallister Hall syndrome, VACTERL/VATER association, and CHARGE syndrome. Laryngeal clefts result from failure of fusion of the posterior cricoid lamina and abnormal development of the tracheo-esophageal septum. The causes of the embryological developmental anomalies leading to LC are not known but are thought to be multifactorial. LC appears to be mostly sporadic although some familial cases with suspected autosomal dominant transmission have been reported. The age of diagnosis depends mainly on the severity of the clinical symptoms and

  17. Divergence in problem-solving skills is associated with differential expression of glutamate receptors in wild finches.

    Science.gov (United States)

    Audet, Jean-Nicolas; Kayello, Lima; Ducatez, Simon; Perillo, Sara; Cauchard, Laure; Howard, Jason T; O'Connell, Lauren A; Jarvis, Erich D; Lefebvre, Louis

    2018-03-01

    Problem solving and innovation are key components of intelligence. We compare wild-caught individuals from two species that are close relatives of Darwin's finches, the innovative Loxigilla barbadensis , and its most closely related species in Barbados, the conservative Tiaris bicolor . We found an all-or-none difference in the problem-solving capacity of the two species. Brain RNA sequencing analyses revealed interspecific differences in genes related to neuronal and synaptic plasticity in the intrapallial neural populations (mesopallium and nidopallium), especially in the nidopallium caudolaterale, a structure functionally analogous to the mammalian prefrontal cortex. At a finer scale, we discovered robust differences in glutamate receptor expression between the species. In particular, the GRIN2B/GRIN2A ratio, known to correlate with synaptic plasticity, was higher in the innovative L. barbadensis . These findings suggest that divergence in avian intelligence is associated with similar neuronal mechanisms to that of mammals, including humans.

  18. The Epidemiology of Cleft Lip and Palate in Canada, 1998 to 2007.

    Science.gov (United States)

    Matthews, Jennifer L K; Oddone-Paolucci, Elizabeth; Harrop, Robertston A

    2015-07-01

    To examine the birth prevalence, gender distribution, and pattern of surgical intervention for clefts in Canada (1998 to 2007). Also to highlight the difficulties associated with studying the epidemiology of clefts using the current data collection mechanisms. Epidemiologic data acquired from the Canadian Institute for Health Information. Population-based study in Canada 1998 to 2007. All live births with an International Classification of Diseases (9th or 10th revision) diagnostic code for cleft palate or for cleft lip with or without cleft palate or with a surgical intervention code for repair of cleft lip or cleft palate. Birth prevalence, gender distribution, and pattern of surgical intervention. There were 3,015,325 live births in Canada (1998 to 2007). The mean birth prevalence was 0.82 per 1000 live births for cleft lip with or without cleft palate and 0.58 per 1000 live births for cleft palate. The birth prevalence of cleft lip with or without cleft palate was significantly higher in boys, with a stable boy to girl ratio of 1.75:1. Cleft palate was significantly greater in girls; however, the boy to girl ratio decreased from 0.97:1 in 1998 to 0.59:1 in 2007. The median age of repair in Canada from 1998 to 2007 was 4.7 months for cleft lip and 11.6 months for cleft palate. Thirty percent of patients underwent cleft palate repair after age 1. The birth prevalence of cleft palate and cleft lip with or without cleft palate is stable in Canada. An increasing birth prevalence of cleft palate in girls is suggested. The timing of surgical intervention is consistent with current standards. The challenges associated with collecting these data in Canada are discussed.

  19. Coordinating structural and functional synapse development: postsynaptic p21-activated kinase independently specifies glutamate receptor abundance and postsynaptic morphology.

    Science.gov (United States)

    Albin, Stephanie D; Davis, Graeme W

    2004-08-04

    Here, we show that postsynaptic p21-activated kinase (Pak) signaling diverges into two genetically separable pathways at the Drosophila neuromuscular junction. One pathway controls glutamate receptor abundance. Pak signaling within this pathway is specified by a required interaction with the adaptor protein Dreadlocks (Dock). We demonstrate that Dock is localized to the synapse via an Src homology 2-mediated protein interaction. Dock is not necessary for Pak localization but is necessary to restrict Pak signaling to control glutamate receptor abundance. A second genetically separable function of Pak kinase signaling controls muscle membrane specialization through the regulation of synaptic Discs-large. In this pathway, Dock is dispensable. We present a model in which divergent Pak signaling is able to coordinate two different features of postsynaptic maturation, receptor abundance, and muscle membrane specialization.

  20. Cleft lip with or without cleft palate and dermatoglyphic asymmetry: evaluation of a Chinese population.

    Science.gov (United States)

    Neiswanger, K; Cooper, M E; Weinberg, S M; Flodman, P; Keglovits, A Bundens; Liu, Y; Hu, D N; Melnick, M; Spence, M A; Marazita, M L

    2002-08-01

    To determine if Chinese individuals with non syndromic cleft lip with or without cleft palate (CL/P) display more dermatoglyphic asymmetry than unaffected relatives or controls. Case-control study with two control groups (genetically related and unrelated). A total of 500 CL/P probands from Shanghai, China, 421 unaffected relatives, and 66 controls of Chinese heritage. Finger and palm prints were collected, and pattern frequencies, total ridge counts (TRC), and atd angles were calculated. Asymmetry scores between right and left hands were defined for each of the three dermatoglyphic measures. Probands' asymmetry scores were compared statistically with the scores of unaffected relatives and controls. In general, the probands' asymmetry scores for TRC and atd angle did not differ significantly from the scores of either unaffected relatives or controls. However, probands with a positive family history of clefting showed significantly more asymmetry in their pattern types than either probands without a family history, unaffected relatives or controls. These results suggest that a unique genetic mechanism of developmental instability may obtain in CL/P individuals with a positive family history of clefting.

  1. Attitudes of pregnant women and mothers of children with orofacial clefts toward prenatal diagnosis of nonsyndromic orofacial clefts in a semiurban set-up in India

    Directory of Open Access Journals (Sweden)

    Poornima Kadagad

    2011-01-01

    Full Text Available Objectives: To assess the attitudes of pregnant women and mothers of children with orofacial clefts toward prenatal diagnosis of clefts and elective termination of pregnancy, and to investigate their opinion about who makes reproductive decisions in the family. Design: Two hundred subjects were included in the study prospectively regarding hypothetical prenatal ultrasound diagnosis of clefts. Setting: The study was done in a private tertiary care institution and a teaching hospital. Subjects/Participants: One hundred pregnant women consulting the Obstetrics department and 100 mothers of children with orofacial clefts in the Cleft and Craniofacial Unit were selected. Materials and Methods: Group I subjects were interviewed using a questionnaire and were shown preoperative and postoperative pictures of children treated for cleft lip and palate. Group II subjects were interviewed using a questionnaire. Results: Only 3% of Group I subjects and 2% of Group II opined that they would choose the elective termination of pregnancy if the fetus was diagnosed with a cleft on an ultrasound scan. In Group II, 70% subjects wished to have known about pregnancy affected with cleft prenatally and 96% said they would definitely avail ultrasound scans to determine pregnancy affected by clefts in future. Conclusions: Majority of the respondents from both the groups chose to continue with the pregnancy affected with a cleft when questioned regarding hypothetical prenatal ultrasound diagnosis of the cleft.

  2. Attitudes of pregnant women and mothers of children with orofacial clefts toward prenatal diagnosis of nonsyndromic orofacial clefts in a semiurban set-up in India

    Science.gov (United States)

    Kadagad, Poornima; Pinto, Pascal; Powar, Rajesh

    2011-01-01

    Objectives: To assess the attitudes of pregnant women and mothers of children with orofacial clefts toward prenatal diagnosis of clefts and elective termination of pregnancy, and to investigate their opinion about who makes reproductive decisions in the family. Design: Two hundred subjects were included in the study prospectively regarding hypothetical prenatal ultrasound diagnosis of clefts. Setting: The study was done in a private tertiary care institution and a teaching hospital. Subjects/Participants: One hundred pregnant women consulting the Obstetrics department and 100 mothers of children with orofacial clefts in the Cleft and Craniofacial Unit were selected. Materials and Methods: Group I subjects were interviewed using a questionnaire and were shown preoperative and postoperative pictures of children treated for cleft lip and palate. Group II subjects were interviewed using a questionnaire. Results: Only 3% of Group I subjects and 2% of Group II opined that they would choose the elective termination of pregnancy if the fetus was diagnosed with a cleft on an ultrasound scan. In Group II, 70% subjects wished to have known about pregnancy affected with cleft prenatally and 96% said they would definitely avail ultrasound scans to determine pregnancy affected by clefts in future. Conclusions: Majority of the respondents from both the groups chose to continue with the pregnancy affected with a cleft when questioned regarding hypothetical prenatal ultrasound diagnosis of the cleft. PMID:22279286

  3. Expression of vesicular glutamate transporters in peripheral vestibular structures and vestibular nuclear complex of rat.

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    Zhang, F X; Pang, Y W; Zhang, M M; Zhang, T; Dong, Y L; Lai, C H; Shum, D K Y; Chan, Y S; Li, J L; Li, Y Q

    2011-01-26

    Glutamate transmission from vestibular end organs to central vestibular nuclear complex (VNC) plays important role in transferring sensory information about head position and movements. Three isoforms of vesicular glutamate transporters (VGLUTs) have been considered so far the most specific markers for glutamatergic neurons/cells. In this study, VGLUT1 and VGLUT2 were immunohistochemically localized to axon terminals in VNC and somata of vestibular primary afferents in association with their central and peripheral axon endings, and VGLUT1 and VGLUT3 were co-localized to hair cells of otolith maculae and cristae ampullaris. VGLUT1 and VGLUT2 defined three subsets of Scarpa's neurons (vestibular ganglionic neurons): those co-expressing VGLUT1 and VGLUT2 or expressing only VGLUT2, and those expressing neither. In addition, many neurons located in all vestibular subnuclei were observed to contain hybridized signals for VGLUT2 mRNA and a few VNC neurons, mostly scattered in medial vestibular nucleus (MVe), displayed VGLUT1 mRNA labelling. Following unilateral ganglionectomy, asymmetries of VGLUT1-immunoreactivity (ir) and VGLUT2-ir occurred between two VNCs, indicating that the VNC terminals containing VGLUT1 and/or VGLUT2 are partly of peripheral origin. The present data indicate that the constituent cells/neurons along the vestibular pathway selectively apply VGLUT isoforms to transport glutamate into synaptic vesicles for glutamate transmission. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Presurgical cleft lip and palate orthopedics: an overview

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    Alzain I

    2017-05-01

    Full Text Available Ibtesam Alzain,1 Waeil Batwa,2 Alex Cash,3 Zuhair A Murshid2 1Pediatric Dentistry, 2Orthodontic Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 3Cleft Lip and Palate Orthodontics, Queen Victoria NHS Foundation Trust, South Thames Cleft Service, London, UK Abstract: Patients with cleft lip and/or palate go through a lifelong journey of multidisciplinary care, starting from before birth and extending until adulthood. Presurgical orthopedic (PSO treatment is one of the earliest stages of this care plan. In this paper we provide a review of the PSO treatment. This review should help general and specialist dentists to better understand the cleft patient care path and to be able to answer patient queries more efficiently. The objectives of this paper were to review the basic principles of PSO treatment, the various types of techniques used in this therapy, and the protocol followed, and to critically evaluate the advantages and disadvantages of some of these techniques. In conclusion, we believe that PSO treatment, specifically nasoalveolar molding, does help to approximate the segments of the cleft maxilla and does reduce the intersegment space in readiness for the surgical closure of cleft sites. However, what we remain unable to prove equivocally at this point is whether the reduction in the dimensions of the cleft presurgically and the manipulation of the nasal complex benefit our patients in the long term. Keywords: presurgical orthopedic, nasoalveolar molding, cleft lip and palate

  5. Reversed synaptic effects of hypocretin and NPY mediated by excitatory GABA-dependent synaptic activity in developing MCH neurons.

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    Li, Ying; Xu, Youfen; van den Pol, Anthony N

    2013-03-01

    In mature neurons, GABA is the primary inhibitory neurotransmitter. In contrast, in developing neurons, GABA exerts excitatory actions, and in some neurons GABA-mediated excitatory synaptic activity is more prevalent than glutamate-mediated excitation. Hypothalamic neuropeptides that modulate cognitive arousal and energy homeostasis, hypocretin/orexin and neuropeptide Y (NPY), evoked reversed effects on synaptic actions that were dependent on presynaptic GABA release onto melanin-concentrating hormone (MCH) neurons. MCH neurons were identified by selective green fluorescent protein (GFP) expression in transgenic mice. In adults, hypocretin increased GABA release leading to reduced excitation. In contrast, in the developing brain as studied here with analysis of miniature excitatory postsynaptic currents, paired-pulse ratios, and evoked potentials, hypocretin acted presynaptically to enhance the excitatory actions of GABA. The ability of hypocretin to enhance GABA release increases inhibition in adult neurons but paradoxically enhances excitation in developing MCH neurons. In contrast, NPY attenuation of GABA release reduced inhibition in mature neurons but enhanced inhibition during development by attenuating GABA excitation. Both hypocretin and NPY also evoked direct actions on developing MCH neurons. Hypocretin excited MCH cells by activating a sodium-calcium exchanger and by reducing potassium currents; NPY reduced activity by increasing an inwardly rectifying potassium current. These data for the first time show that both hypocretin and NPY receptors are functional presynaptically during early postnatal hypothalamic development and that both neuropeptides modulate GABA actions during development with a valence of enhanced excitation or inhibition opposite to that of the adult state, potentially allowing neuropeptide modulation of use-dependent synapse stabilization.

  6. Genetic association studies of glutamate, GABA and related genes in schizophrenia and bipolar disorder: a decade of advance.

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    Cherlyn, Suat Ying Tan; Woon, Puay San; Liu, Jian Jun; Ong, Wei Yi; Tsai, Guo Chuan; Sim, Kang

    2010-05-01

    Schizophrenia (SZ) and bipolar disorder (BD) are debilitating neurobehavioural disorders likely influenced by genetic and non-genetic factors and which can be seen as complex disorders of synaptic neurotransmission. The glutamatergic and GABAergic neurotransmission systems have been implicated in both diseases and we have reviewed extensive literature over a decade for evidence to support the association of glutamate and GABA genes in SZ and BD. Candidate-gene based population and family association studies have implicated some ionotrophic glutamate receptor genes (GRIN1, GRIN2A, GRIN2B and GRIK3), metabotropic glutamate receptor genes (such as GRM3), the G72/G30 locus and GABAergic genes (e.g. GAD1 and GABRB2) in both illnesses to varying degrees, but further replication studies are needed to validate these results. There is at present no consensus on specific single nucleotide polymorphisms or haplotypes associated with the particular candidate gene loci in these illnesses. The genetic architecture of glutamate systems in bipolar disorder need to be better studied in view of recent data suggesting an overlap in the genetic aetiology of SZ and BD. There is a pressing need to integrate research platforms in genomics, epistatic models, proteomics, metabolomics, neuroimaging technology and translational studies in order to allow a more integrated understanding of glutamate and GABAergic signalling processes and aberrations in SZ and BD as well as their relationships with clinical presentations and treatment progress over time. (c) 2010 Elsevier Ltd. All rights reserved.

  7. Zinc at glutamatergic synapses.

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    Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

    2009-01-12

    It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

  8. Ectrodactyly-ectodermal dysplasia-cleft lip and palate syndrome

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    Reema Sharma Dhar

    2014-01-01

    Full Text Available Ectrodactyly-ectodermal dysplasia-cleft (EEC syndrome is an autosomal dominant disorder characterized by the triad of ectrodactyly-ectodermal dysplasia, and facial clefting along with some associated features. Presence of all the three major features in a single individual is extremely rare. We report a case of 4 year 11 months old child with EEC syndrome having ectodermal dysplasia-cleft lip and cleft palate and ectrodactyly with some associated features. Clinical features, diagnosis and role of a dentist in the multidisciplinary treatment approach have been elaborated in this case report.

  9. Ectrodactyly-ectodermal dysplasia-cleft lip and palate syndrome.

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    Dhar, Reema Sharma; Bora, Amitava

    2014-01-01

    Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome is an autosomal dominant disorder characterized by the triad of ectrodactyly-ectodermal dysplasia, and facial clefting along with some associated features. Presence of all the three major features in a single individual is extremely rare. We report a case of 4 year 11 months old child with EEC syndrome having ectodermal dysplasia-cleft lip and cleft palate and ectrodactyly with some associated features. Clinical features, diagnosis and role of a dentist in the multidisciplinary treatment approach have been elaborated in this case report.

  10. Dental Anomalies in a Brazilian Cleft Population.

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    Sá, Jamile; Mariano, Lorena C; Canguçu, Daiane; Coutinho, Thaynara S L; Hoshi, Ryuichi; Medrado, Alena Peixoto; Martelli-Junior, Hercílio; Coletta, Ricardo D; Reis, Silvia R A

    2016-11-01

      The aim of this study was to radiographically investigate the prevalence of dental anomalies outside the cleft area in a group of Brazilian patients with nonsyndromic cleft lip and/or palate (NSCL/P).   A retrospective analysis of 207 panoramic radiographs of patients with NSCL/P aged 12 to 45 years without history of tooth extraction and orthodontic treatment was performed.   Dental anomalies were found in 75.4% of the patients, and tooth agenesis (29.2%) and supernumerary tooth (2.6%) were the most common anomalies. The risk of agenesis was higher among the individuals with cleft palate (CP) compared with individuals with cleft lip (CL) and cleft lip and palate (CLP) (agenesis: CP versus CL: odds ratio 6.27, 95% confidence interval 2.21-17.8, P = .0003; CP versus CLP: odds ratio 2.94; 95% confidence interval 1.27-6.81, P = .01). The frequency of dental agenesis was higher in patients with unilateral complete CLP (agenesis: P dental agenesis (P dental anomalies in patients with NSCL/P was higher than that reported in overall population. This study found preferential associations between dental anomalies and specific extensions of NSCL/P, suggesting that dental agenesis and ectopic tooth may be part of oral cleft subphenotypes.

  11. When there is more than a cleft: psychological adjustment when a cleft is associated with an additional condition.

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    Feragen, Kristin Billaud; Stock, Nicola Marie

    2014-01-01

    In spite of studies reporting a relatively high frequency of additional conditions in children with a cleft lip and/or cleft palate (CL/P), almost no research has focused on this clinically important subgroup. The objective of this study was to compare psychosocial adjustment in children with CL/P with and without an additional condition. Cross-sectional data based on routine psychological assessments at age 10 years, with comparisons to national reference groups. Centralized treatment, Norway. Two hundred five children with CL/P (participation rate: 80.1%) from three consecutive birth cohorts. The Strengths and Difficulties Questionnaire (self-report and parent report) and the Child Experience Questionnaire (self-report). Eighty-one children (39.5%) were identified as having at least one condition in addition to the cleft. These children reported significantly more psychosocial difficulties than children with a cleft alone. Differences between specific conditions were minor. Children with a cleft alone (n = 124) reported mean scores that were comparable to those reported by the reference group. There were no differences in adjustment between children with a visible versus a non-visible cleft. The present study highlights the need for research to be conducted in children with CL/P who have additional conditions to provide better knowledge and clinical care for a potentially vulnerable subgroup of children and their parents.

  12. Submucous Clefts

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    ... Find Local Cleft/Craniofacial Specialists Booklets & Factsheets College Scholarships School-Age Support Resources Connections Conference View More… ... for speech problems, middle ear disease, and swallowing difficulties. However, there are some individuals with a submucous ...

  13. A cross-sectional analysis of the prevalence of tooth agenesis and structural dental anomalies in association with cleft type in non-syndromic oral cleft patients.

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    Konstantonis, Dimitrios; Alexandropoulos, Alexandros; Konstantoni, Nikoleta; Nassika, Maria

    2017-12-01

    The aim of this study was to investigate the prevalence of tooth agenesis, microdontia, and tooth malformation among non-syndromic oral cleft patients and their potential association with cleft type and gender. Intraoral records and radiographs of 154 patients (97 males and 57 females) were examined. The variables assessed were tooth agenesis, microdontia, dental malformations, and cleft types. The statistics included chi-square and Fisher's exact tests as well as logistic regression to assess any mutual effects of gender and cleft type on the dental variables. Tooth agenesis occurred in 50% of the sample and microdontia in 18%. Non-statistically significant odds ratios for the association of gender and cleft type with tooth agenesis were obtained. Tooth agenesis was substantially higher at the unilateral right CL + P and the bilateral CL + P in quadrant 1 and at the unilateral left CL + P and bilateral CL + P in quadrant 2. It was also higher, at the isolated cleft palate (CP) in quadrants 3 and 4. These results were attributed to teeth 22 (31.8%) and 12 (21.6%) in the maxilla and to teeth 35 (6.1%) and 45 (5.4%) in the mandible. In unilateral CL + P patients, the cleft quadrant that presented tooth agenesis was associated with the side of the cleft. Interdisciplinary treatment of the oral cleft patients should take into consideration the high prevalence of tooth agenesis and their association with the different cleft types. The most frequently affected teeth by cleft are by far the upper lateral incisors. Results indicate that tooth agenesis appears to be a genetically controlled anomaly related to the orofacial cleft development through various genetic links and not caused by the cleft disruptive process.

  14. Novel 3-D Analysis for the Assessment of Cleft Dimensions on Digital Models of Infants With Unilateral Cleft Lip and Palate

    DEFF Research Database (Denmark)

    Botticelli, Susanna; Pedersen, Thomas Klit; Küseler, Annelise

    2018-01-01

    OBJECTIVE: To present a 3-D standardized analysis of cleft dimensions. MATERIALS: Thirty-one plaster casts of unilateral cleft lip and palate (UCLP) infants were laser scanned. Landmarks and coordinate system were defined. Linear distances and surfaces were measured, and the ratio between cleft...... and palatal area was calculated (3-D infant cleft severity ratio [3D ICSR]). The digitally measured areas were compared with silicone membranes, adapted to the plaster casts, and analyzed by optic microscopy. MAIN OUTCOME MEASURES: Repeatability, reproducibility, and validity. RESULTS: Bland-Altman plots...

  15. Magnetic resonance imaging of cleft palate

    Energy Technology Data Exchange (ETDEWEB)

    Naito, Yasushi; Tasaka, Yasuyuki; Honjo, Iwao; Nishimura, Kazumasa; Nakano, Yoshihisa

    1987-03-01

    Magnetic resonance imaging (MRI) of the nasopharynx and the eustachian tube was performed in five patients with cleft palate and compared with the results of those without this anomaly. Various degrees of deformity of the eustachian tube cartilage were found in cleft palate patients. The levator veli palatini muscles were situated more laterally in cleft palate patients than in normal subjects. Also, changes in the position of these muscles after palatoplasty were clearly depicted by MRI. Besides several autopsy reports, this is the first demonstration of the characteristic anomaly around the eustachian tube by a non-invasive method.

  16. Africa has unique and urgent barriers to cleft care: lessons from practitioners at the Pan-African Congress on Cleft Lip and Palate.

    Science.gov (United States)

    Adetayo, Oluwaseun; Ford, Rachel; Martin, Mark

    2012-01-01

    The goals of this study were to delineate the protocols employed for managing patients with cleft lip and palate deformities, delineate the challenges facing practitioners and patients, and to determine the patient and physician barriers to cleft care delivery in the region. Survey questionnaires were administered to practitioners attending the second Pan-African Congress on Cleft Lip and Palate (PACCLIP), which took place in Ibadan, Nigeria, West Africa from February 4-7, 2007. The conference included 225 participants, representing 17 African countries Protocols for repair of cleft lip and palate deformities were varied, with Millard's and von Langenbeck's techniques being the preferred approach for the management of cleft lip and palate deformities, respectively. A large proportion of providers have limited access to core cleft care supporting teams, especially speech language pathologists, orthodontists, and audiologists. Several challenging barriers to cleft care were also identified at both the institutional and individual levels and are reported. Geographic separation in Africa presents a similar challenge due to isolationism as it does to surgeons in Europe. Specific to Africa are the increased barriers to care, and economic and financial hardship at various levels. A focus on funding, team building, infrastructural support, and patient education appear to be crucial in improving the care and lives of children with facial clefts in Africa.

  17. A comparative study of prelinguistic vocalizations in two groups of cleft toddlers and a non-cleft group

    DEFF Research Database (Denmark)

    Willadsen, Elisabeth; Enemark, Hans

    2000-01-01

    . The results of this investigation were compared to results previously reported for 19 children with cleft palate and 19 noncleft children at the age of 13 months. The children with clefts in that study received a two-stage palatal surgery. This surgical procedure was formerly used at our center and included...... children in the comparison group. Both groups of subjects with clefts had significantly fewer plosives in their contoid inventory than the noncleft group, and there was no difference regarding place of articulation between the group that received delayed closure of the hard palate and the noncleft group.......Objective: This study examined the prelinguistic contoid (consonant-like) inventories of 14 children with unilateral cleft lip and palate (C-UCLP) at 13 months of age. The children had received primary veloplasty at 7 months of age and closure of the hard palate was performed at 3–5 years...

  18. Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging.

    Science.gov (United States)

    Lalo, Ulyana; Rasooli-Nejad, Seyed; Pankratov, Yuriy

    2014-10-01

    Maintaining brain function during aging is very important for mental and physical health. Recent studies showed a crucial importance of communication between two major types of brain cells: neurons transmitting electrical signals, and glial cells, which maintain the well-being and function of neurons. Still, the study of age-related changes in neuron-glia signalling is far from complete. We have shown previously that cortical astrocytes are capable of releasing ATP by a quantal soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complex-dependent mechanism. Release of ATP from cortical astrocytes can be activated via various pathways, including direct UV-uncaging of intracellular Ca²⁺ or G-protein-coupled receptors. Importantly, release of both ATP and glutamate from neocortical astrocytes was not observed in brain slices of dominant-negative SNARE (dnSNARE) mice, expressing dnSNARE domain selectively in astrocytes. We also discovered that astrocyte-driven ATP can cause significant attenuation of synaptic inhibition in the pyramidal neurons via Ca²⁺-interaction between the neuronal ATP and γ-aminobutyric acid (GABA) receptors. Furthermore, we showed that astrocyte-derived ATP can facilitate the induction of long-term potentiation of synaptic plasticity in the neocortex. Our recent data have shown that an age-related decrease in the astroglial Ca²⁺ signalling can cause a substantial decrease in the exocytosis of gliotransmitters, in particular ATP. Age-related impairment of ATP release from cortical astrocytes can cause a decrease in the extent of astroglial modulation of synaptic transmission in the neocortex and can therefore contribute to the age-related impairment of synaptic plasticity and cognitive decline. Combined, our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function.

  19. First branchial cleft anomalies: avoiding the misdiagnosis.

    Science.gov (United States)

    Kumar, Rajeev; Sikka, Kapil; Sagar, Prem; Kakkar, Aanchal; Thakar, Alok

    2013-07-01

    First branchial cleft anomalies are a very rare entities accounting for less than 1 % of all branchial cleft malformations. They are often misdiagnosed for other cystic lesions occurring in parotid gland and inadequately treated (incision and drainage or incomplete excision) leading to multiple recurrences. We report a series of four patients who were previously operated (incision and drainage) for misdiagnosed first branchial cleft anomalies with subsequent recurrences. All patients underwent superficial parotidectomy with complete tract excision using facial nerve monitoring to prevent iatrogenic injury because of extensive fibrosis. We discuss the literature pertaining to first branchial cleft anomalies, their varied presentations and their relationship to facial nerve in parotid gland and importance of facial nerve monitoring in revision surgery.

  20. Transverse facial cleft: A series of 17 cases

    Directory of Open Access Journals (Sweden)

    L K Makhija

    2011-01-01

    Full Text Available Introduction: Transverse facial cleft (Tessier type 7 or congenital macrostomia is a rare congenital anomaly seldom occurring alone and is frequently associated with deformities of the structures developing from the first and second branchial arches. The reported incidence of No. 7 cleft varies from 1 in 60,000 to 1 in 300,000 live births. Material and Methods: Seventeen patients of transeverse facial cleft who presented to us in last 5 years were included in the study. Their history regarding familial and environmental predispositions was recorded. The cases were analysed on basis of sex, laterality, severity, associated anomalies and were graded according to severity. They were operated by z plasty technique and were followed up for 2 years to look for effectiveness of the technique and its complications. Result: Out of the seventeen patients of transverse cleft, none had familial predilection or any environmental etiology like antenatal radiological exposure or intake of drugs of teratogenic potential. Most of the patients (9/17 were associated with hemifacial microsomia and 1 patient was associated with Treacher Colin′s Syndrome. Out of the 6 cases of Grade I clefts, 4 were isolated transverse clefts and of the 10 patients of Grade II clefts, 7 were associated with hemifacial microsomia. We encountered only one case of Grade III Transverse Cleft which was not only associated with hemifacial microsomia but also had cardiac anomaly. Out of the17 cases, 15 were operated and in most of them the outcome was satisfactory.

  1. Congenital Palatal Fistula Associated with Submucous Cleft Palate

    Science.gov (United States)

    Eshete, Mekonen; Camison, Liliana; Abate, Fikre; Hailu, Taye; Demissie, Yohannes; Mohammed, Ibrahim; Butali, Azeez; Losken, H. Wolfgang

    2016-01-01

    Background: Although cleft lip and cleft palate are among the most common congenital malformations, the presence of an isolated congenital palatal fistula along with a submucous cleft is very rare. This appears as an oval-shaped, full-thickness fenestration in the palatal midline that does not fully extend anteriorly or posteriorly, accompanied by the findings of a submucous cleft. Because of the uncommon nature of this entity, there is controversy about its etiology, diagnosis, and management. Methods: Two cases of children with congenital palatal fistulae and a submucous cleft palate are presented who were treated in different settings by different surgeons. Cases are discussed along with a thorough review of the available literature. Results: Patient 1 presented at 4 years of age with “a hole in the palate” since birth and abnormal speech. His palatal fistula and submucous cleft were repaired with a modified von Langenbeck technique in Ethiopia. At a 2-year follow-up, the palate remained closed, but hypernasal speech persisted. Patient 2 was a 1-year-old presenting with failure to thrive and nasal regurgitation, who underwent a Furlow palatoplasty in the United States with good immediate results. She was unfortunately lost to follow-up. Conclusions: A congenital fenestration of the palate is rare. Reports reveal suboptimal speech at follow-up, despite various types of repair, especially when combined with a submucous cleft. Available literature suggests that repair should not focus on fistula closure only but instead on providing adequate palate length to provide good velopharyngeal function, as in any cleft palate repair. PMID:27014542

  2. Cadmium action in synapses in the brain

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    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto [Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan)

    2001-05-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of {sup 109}CdCl{sub 2} into the amygdala of rats, {sup 109}Cd release into the extracellular space was facilitated by stimulation with high K{sup +}, suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 {mu}M CdCl{sub 2}. The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and {gamma}-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  3. Orthognathic surgery in cleft patients.

    Science.gov (United States)

    Phillips, John H; Nish, Iain; Daskalogiannakis, John

    2012-03-01

    After studying this article, the participant should be able to: 1. Identify the skeletal changes in the cleft patient that necessitate surgery. 2. Describe the orthodontic principles that precede surgical treatment. 3. Demonstrate the surgical principles involved in cleft orthognathic surgery and how to avoid common pitfalls particular to cleft orthognathic surgery. 4. Anticipate when dentoalveolar distraction can help in the treatment of problems not easily treated with conventional orthognathic techniques. This CME article covers the basic multidisciplinary approach to the treatment of patients requiring a combined orthodontic orthognathic approach to their skeletally based malocclusion. The dentoskeletal abnormalities are described for these patients, as are the fundamental orthodontic principles in the presurgical treatment of these patients. The basic surgical principles are discussed in general, and the reader is provided with advice on avoiding common pitfalls. Specific attention is given to the more recent advances in dentoalveolar distraction in cases of large defects that would have been difficult to treat using conventional orthognathic surgery. Videos are provided to illustrate the general principles in treating the cleft orthognathic patient and to illustrate the treatment of large defects using dentoalveolar distraction.

  4. Simulating clefts in pumpkin balloons

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    Baginski, Frank; Brakke, Kenneth

    2010-02-01

    The geometry of a large axisymmetric balloon with positive differential pressure, such as a sphere, leads to very high film stresses. These stresses can be significantly reduced by using a tendon re-enforced lobed pumpkin-like shape. A number of schemes have been proposed to achieve a cyclically symmetric pumpkin shape, including the constant bulge angle (CBA) design, the constant bulge radius (CBR) design, CBA/CBR hybrids, and NASA’s recent constant stress (CS) design. Utilizing a hybrid CBA/CBR pumpkin design, Flight 555-NT in June 2006 formed an S-cleft and was unable to fully deploy. In order to better understand the S-cleft phenomenon, a series of inflation tests involving four 27-m diameter 200-gore pumpkin balloons were conducted in 2007. One of the test vehicles was a 1/3-scale mockup of the Flight 555-NT balloon. Using an inflation procedure intended to mimic ascent, the 1/3-scale mockup developed an S-cleft feature strikingly similar to the one observed in Flight 555-NT. Our analysis of the 1/3-scale mockup found it to be unstable. We compute asymmetric equilibrium configurations of this balloon, including shapes with an S-cleft feature.

  5. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

    Science.gov (United States)

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

    High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

  6. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

    Science.gov (United States)

    Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

  7. Changing lifestyles and oral clefts occurrence in Denmark

    DEFF Research Database (Denmark)

    Bille, Camilla; Knudsen, Lisbeth B.; Christensen, Kaare

    2005-01-01

    ; furthermore, smoking among pregnant women decreased considerably. Design and settings There are few places in which ecological studies of oral clefts are possible. Denmark provides a particularly good setting for this kind of study, due to a high ascertainment and a centralized registration of cleft cases...... through the last 65 years. Participants Cleft occurrence in Denmark 1936 to 1987 has previously been reported. Here we extend the study to include all live-born children with oral clefts born in Denmark in 1988 throguh 2001. Among a total of 992,727 live births 1332 children with CL(P) were born during...

  8. Lateral cervical cleft: a previously unreported anomaly resulting from incomplete disappearance of the second pharyngeal (branchial) cleft.

    Science.gov (United States)

    Gürsoy, M H; Gedikoğlu, G; Tanyel, F C

    1999-03-01

    The authors present a 2-year-old boy with a skin defect located in the right lateral side of the neck. They suggest the defect is a partial failure of disappearance of the second pharyngeal (branchial) cleft and propose a name of lateral cervical cleft.

  9. Structure-Function Relationship of Transporters in the Glutamate–Glutamine Cycle of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Mariko Kato Hayashi

    2018-04-01

    Full Text Available Many kinds of transporters contribute to glutamatergic excitatory synaptic transmission. Glutamate is loaded into synaptic vesicles by vesicular glutamate transporters to be released from presynaptic terminals. After synaptic vesicle release, glutamate is taken up by neurons or astrocytes to terminate the signal and to prepare for the next signal. Glutamate transporters on the plasma membrane are responsible for transporting glutamate from extracellular fluid to cytoplasm. Glutamate taken up by astrocyte is converted to glutamine by glutamine synthetase and transported back to neurons through glutamine transporters on the plasma membranes of the astrocytes and then on neurons. Glutamine is converted back to glutamate by glutaminase in the neuronal cytoplasm and then loaded into synaptic vesicles again. Here, the structures of glutamate transporters and glutamine transporters, their conformational changes, and how they use electrochemical gradients of various ions for substrate transport are summarized. Pharmacological regulations of these transporters are also discussed.

  10. The second branchial cleft fistula.

    Science.gov (United States)

    Maddalozzo, John; Rastatter, Jeffrey C; Dreyfuss, Heath F; Jaffar, Reema; Bhushan, Bharat

    2012-07-01

    To review the surgical anatomy and histopathology of second branchial cleft fistulae. Retrospective study of patients treated for second branchial cleft fistulae at a tertiary care pediatric hospital. The senior author noted anatomic and histologic features of second branchial cleft fistulae, not previously described. Tertiary care children's hospital. Retrospective examination of 28 patients was conducted who were operated upon for second branchial cleft fistula. Data collected included age at surgery, initial presentation, imaging characteristics prior to surgery, laterality of the fistula tract, pathology results and follow-up data. Twenty-eight patients met the criteria for inclusion. Three patients (11%) had bilateral fistulae. 11 (39%) were male and 17 (61%) were female. 23 (74.2%) tracts were lined with ciliated columnar epithelium, 3 (9.7%) had cuboidal epithelium, and 5 (16.7%) had squamous epithelium. Nineteen (61.3%) tracts contained salivary tissue. Of the unilateral fistula tracts, 25 (100%) were on the right side. Of the 3 patients with bilateral lesions, 2 (66%) had associated branchio-oto-renal syndrome (BORS). Second branchial cleft fistulae are rare. They are usually right-sided. If bilateral fistulae are present, one should consider an underlying genetic disorder. The histology of the fistulae mostly demonstrates ciliated columnar epithelium with the majority of specimens showing salivary tissue. There is a clear association with the internal jugular vein (IJV). Dissection should continue until superior to the hyoid bone, ensuring near complete surgical dissection and less risk of recurrence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Metabolic Turnover of Synaptic Proteins: Kinetics, Interdependencies and Implications for Synaptic Maintenance

    Science.gov (United States)

    Cohen, Laurie D.; Zuchman, Rina; Sorokina, Oksana; Müller, Anke; Dieterich, Daniela C.; Armstrong, J. Douglas; Ziv, Tamar; Ziv, Noam E.

    2013-01-01

    Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non–Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2–5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load

  12. Exclusion of linkage between cleft lip with or without cleft palate and markers on chromosomes 4 and 6

    Energy Technology Data Exchange (ETDEWEB)

    Blanton, S.H. [Univ. of Virginia, Charlottesville, VA (United States); Malcolm, S.; Winter, R. [Institute of Child Health, London (United Kingdom)] [and others

    1996-01-01

    Nonsyndromic cleft lip with or without associate cleft palate (CLP) is a common craniofacial defect, occurring in {approximately}1/1,000 live births. While the defect generally occurs sporadically, multiplex families have been reported. Segregation analyses have demonstrated that, in some families, CLP is inherited as an autosomal dominant/codominant disorder with low penetrance. Several clefting loci have been proposed on multiple chromosomes, including 6p24, 4q, and 19q13.1. Association studies and linkage studies suggested a locus that mapped to 6p24. We were unable to confirm this in a linkage study of 12 multigenerational families. A subsequent linkage study by Carinci et al., however, found evidence for linkage to this region in 14 of 21 clefting families. Additionally, Davies et al. studied the chromosomes of three individuals with cleft lip and palate, all of whom had a rearrangement involving 6p24. Their investigation supported a locus at 6p24. Carinci et al. reported that the most likely position for a clefting locus was at D6S89, which is centromeric to EDN1. This is in contrast to the findings of Davies et al., who suggested a placement telomeric to EDN1. F13A, which had been implicated in the initial association studies, is telomeric to EDN1. Thus, the region between F13A and D6S89 encompasses the regions proposed by both Davies et al. and Carinci et al. A second clefting locus, at 4q, was proposed by Beiraghi et al., who studied a single multigenerational family by linkage analysis. Their data suggested a locus near D4S175 and D4S192. 10 refs., 1 tab.

  13. Psychometric findings and normative values for the CLEFT-Q based on 2434 children and young adult patients with cleft lip and/or palate from 12 countries

    Science.gov (United States)

    Riff, Karen WY Wong; Longmire, Natasha M.; Albert, Asteria; Allen, Gregory C.; Aydin, Mustafa Asim; Baker, Stephen B.; Cano, Stefan J.; Chan, Andrew J.; Courtemanche, Douglas J.; Dreise, Marieke M.; Goldstein, Jesse A.; Goodacre, Timothy E.E.; Harman, Karen E.; Munill, Montserrat; Mahony, Aisling O.; Aguilera, Mirta Palomares; Peterson, Petra; Pusic, Andrea L.; Slator, Rona; Stiernman, Mia; Tsangaris, Elena; Tholpady, Sunil S.; Vargas, Federico; Forrest, Christopher R.

    2018-01-01

    BACKGROUND: Patients with cleft lip and/or palate can undergo numerous procedures to improve appearance, speech, dentition and hearing. We developed a cleft-specific patient-reported outcome instrument to facilitate rigorous international measurement and benchmarking. METHODS: Data were collected from patients aged 8–29 years with cleft lip and/or palate at 30 hospitals in 12 countries between October 2014 and November 2016. Rasch measurement theory analysis was used to refine the scales and to examine reliability and validity. Normative CLEFT-Q values were computed for age, sex and cleft type. RESULTS: Analysis led to the refinement of an eating and drinking checklist and 12 scales measuring appearance (of the face, nose, nostrils, teeth, lips, jaws and cleft lip scar), health-related quality of life (psychological, social, school, speech distress) and speech function. All scales met the requirements of the Rasch model. Analysis to explore differential item functioning by age, sex and country provided evidence to support the use of a common scoring algorithm for each scale for international use. Lower (worse) scores on CLEFT-Q scales were associated with having a speech problem, being unhappy with facial appearance, and needing future cleft-related treatments, providing evidence of construct validity. Normative values for age, sex and cleft type showed poorer outcomes associated with older age, female sex and having a visible cleft. INTERPRETATION: The CLEFT-Q represents a rigorously developed instrument that can be used internationally to collect and compare evidence-based outcomes data from patients aged 8–29 years of age with cleft lip and/or palate. PMID:29661814

  14. Blood Glutamate Scavenging: Insight into Neuroprotection

    Directory of Open Access Journals (Sweden)

    Alexander Zlotnik

    2012-08-01

    Full Text Available Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.

  15. Risk of Oral Clefts in Twins

    DEFF Research Database (Denmark)

    Grosen, Dorthe; Bille, Camilla; Petersen, Inge

    2011-01-01

    and heritability. Twins (207 affected/130,710) and singletons (7766 affected/4,798,526) born from 1936 through 2004 in Denmark were ascertained by linkage among the Danish Facial Cleft Database, the Danish Twin Registry, and the Civil Registration System. We computed oral cleft prevalence and prevalence proportion...

  16. Variations in Velopharyngeal Structure in Adults With Repaired Cleft Palate.

    Science.gov (United States)

    Perry, Jamie L; Kotlarek, Katelyn J; Sutton, Bradley P; Kuehn, David P; Jaskolka, Michael S; Fang, Xiangming; Point, Stuart W; Rauccio, Frank

    2018-01-01

    The purpose of this study was to examine differences in velopharyngeal structures between adults with repaired cleft palate and normal resonance and adults without cleft palate. Thirty-six English-speaking adults, including 6 adults (2 males and 4 females) with repaired cleft palate (M = 32.5 years of age, SD = 17.4 years) and 30 adults (15 males and 15 females) without cleft palate (M = 23.3 years of age, SD = 4.1 years), participated in the study. Fourteen velopharyngeal measures were obtained on magnetic resonance images and compared between groups (cleft and noncleft). After adjusting for body size and sex effects, there was a statistically significant difference between groups for 10 out of the 14 velopharyngeal measures. Compared to those without cleft palate, participants with repaired cleft palate had a significantly shorter hard palate height and length, shorter levator muscle length, shorter intravelar segment, more acute levator angles of origin, shorter and thinner velum, and greater pharyngeal depth. Although significant differences were evident in the cleft palate group, individuals displayed normal resonance. These findings suggest that a wide variability in velopharyngeal anatomy can occur in the presence of normal resonance, particularly for those with repaired cleft palate. Future research is needed to understand how anatomic variability impacts function, such as during speech.

  17. Assessment of nostril symmetry after primary cleft rhinoplasty in patients with complete unilateral cleft lip and palate

    NARCIS (Netherlands)

    Reddy, S.G.; Devarakonda, V.; Reddy, RR

    2013-01-01

    The aim of this study was to assess the nostril symmetry following primary cleft rhinoplasty done with either a dorsal onlay or columellar strut graft in patients with non-syndromic complete unilateral cleft lip and palate. In this retrospective study 30 consecutive patients treated with autogenous

  18. Cone-Beam Computed Tomography Assessment of Lower Facial Asymmetry in Unilateral Cleft Lip and Palate and Non-Cleft Patients with Class III Skeletal Relationship.

    Science.gov (United States)

    Lin, Yifan; Chen, Gui; Fu, Zhen; Ma, Lian; Li, Weiran

    2015-01-01

    To evaluate, using cone-beam computed tomography (CBCT), both the condylar-fossa relationships and the mandibular and condylar asymmetries between unilateral cleft lip and palate (UCLP) patients and non-cleft patients with class III skeletal relationship, and to investigate the factors of asymmetry contributing to chin deviation. The UCLP and non-cleft groups consisted of 30 and 40 subjects, respectively, in mixed dentition with class III skeletal relationships. Condylar-fossa relationships and the dimensional and positional asymmetries of the condyles and mandibles were examined using CBCT. Intra-group differences were compared between two sides in both groups using a paired t-test. Furthermore, correlations between each measurement and chin deviation were assessed. It was observed that 90% of UCLP and 67.5% of non-cleft subjects had both condyles centered, and no significant asymmetry was found. The axial angle and the condylar center distances to the midsagittal plane were significantly greater on the cleft side than on the non-cleft side (P=0.001 and P=0.028, respectively) and were positively correlated with chin deviation in the UCLP group. Except for a larger gonial angle on the cleft side, the two groups presented with consistent asymmetries showing shorter mandibular bodies and total mandibular lengths on the cleft (deviated) side. The average chin deviation was 1.63 mm to the cleft side, and the average absolute chin deviation was significantly greater in the UCLP group than in the non-cleft group (P=0.037). Compared with non-cleft subjects with similar class III skeletal relationships, the subjects with UCLP showed more severe lower facial asymmetry. The subjects with UCLP presented with more asymmetrical positions and rotations of the condyles on axial slices, which were positively correlated with chin deviation.

  19. [Double second branchial cleft anomaly].

    Science.gov (United States)

    Muñoz-Fernández, Noelia; Mallea-Cañizares, Ismael; Fernández-Julián, Enrique; De La Fuente-Arjona, Luís; Marco-Algarra, Jaime

    2011-01-01

    Second branchial cleft anomalies are the most common of this type of neck masses. They can be classified in four types (Bailey/Proctor classification) according to their location. Type II is the most common, and related to vital neck structures such as the carotid artery and jugular vein. Cysts are the most frequent among them. Management consists of surgical excision of the cyst and tract by cervicotomy to avoid recurrence. We present an extremely rare case of a 32-year-old male who presented a sudden appearance of a right lateral neck mass that was identified by an image study as a double branchial cleft cyst. A review of simultaneous branchial cleft cyst in the literature is also made. Copyright © 2009 Elsevier España, S.L. All rights reserved.

  20. Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones.

    Science.gov (United States)

    Evstratova, Alesya; Tóth, Katalin

    2011-12-01

    The co-release of neuromodulatory substances in combination with classic neurotransmitters such as glutamate and GABA from individual presynaptic nerve terminals has the capacity to dramatically influence synaptic efficacy and plasticity. At hippocampal mossy fibre synapses vesicular zinc is suggested to serve as a cotransmitter capable of regulating calcium release from internal stores in postsynaptic CA3 pyramidal cells. Here we investigated this possibility using combined intracellular ratiometric calcium imaging and patch-clamp recording techniques. In acute hippocampal slices a brief train of mossy fibre stimulation produced a large, delayed postsynaptic Ca(2+) wave that was spatially restricted to the proximal apical dendrites of CA3 pyramidal cells within stratum lucidum. This calcium increase was sensitive to intracellularly applied heparin indicating reliance upon release from internal stores and was triggered by activation of both group I metabotropic glutamate and NMDA receptors. Importantly, treatment of slices with the membrane-impermeant zinc chelator CaEDTA did not influence the synaptically evoked postsynaptic Ca(2+) waves. Moreover, mossy fibre stimulus evoked postsynaptic Ca(2+) signals were not significantly different between wild-type and zinc transporter 3 (ZnT3) knock-out animals. Considered together our data do not support a role for vesicular zinc in regulating mossy fibre evoked Ca(2+) release from CA3 pyramidal cell internal stores.

  1. Swallowing function after laryngeal cleft repair: more than just fixing the cleft.

    Science.gov (United States)

    Osborn, Alexander J; de Alarcon, Alessandro; Tabangin, Meredith E; Miller, Claire K; Cotton, Robin T; Rutter, Michael J

    2014-08-01

    To evaluate and describe the swallowing function in children after laryngeal cleft repair. Ten-year (2002-2012) retrospective chart review. Academic tertiary care pediatric otolaryngology practice. Records of 60 children who had surgical repair of laryngeal cleft (ages 2 weeks-14 years) and postoperative functional endoscopic evaluation of swallowing or videofluoroscopic swallow studies were examined retrospectively. Twenty-nine children had one postoperative swallow evaluation, 19 children had two, 4 children had three, 5 children had four, and 3 children had five. Median time to the first evaluation was 10.8 weeks (interquartile range [IQR]: 36.5, 231). On the final swallow evaluation, 34 (57%) children demonstrated normal swallowing parameters, 12 (20%) children showed penetration, and 14 (23%) children showed aspiration. Forty-three (72%) children were able to take everything by mouth normally or with minor behavioral modifications, 11 (18%) children required thickened fluids, and six (10%) children were kept nil per os (NPO). Mean improvement on the penetration-aspiration (pen-asp) scale was 2.13. On multivariable analysis, neurodevelopmental issues and gastronomy tube use were associated with the need for NPO status. Despite a high rate of surgical success, a substantial minority of children have persistent swallowing dysfunction after laryngeal cleft repair. Swallowing dysfunction after repair is multifactorial and arises from concomitant neurologic, anatomic, or other comorbidities that contribute to oropharyngeal and pharyngeal dysphagia. Based on our results, we recommend a testing schedule for postoperative swallowing evaluations after cleft repair. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  2. #Cleft: The use of Social Media Amongst Parents of Infants with Clefts.

    Science.gov (United States)

    Khouri, Joseph S; McCheyne, Melisande J; Morrison, Clinton S

    2018-01-01

    Introduction Many societies and organizations are using social media to reach their target audience. The extent to which parents of patients with craniofacial anomalies use social media has yet to be determined. The goal of this study is to characterize and describe the use of social media by the parents of children with cleft lip and palate as it pertains to the care of their child. Materials and Methods Parents or guardian of all patients presenting for initial consultation regarding a child's congenital cleft anomaly were contacted by phone or mail to complete a survey regarding their use of social media vis-à-vis their child's cleft anomaly. Participants were asked to answer a 19-question survey. Results Thirty-two families were contacted and 25 surveys were completed. Ninety-two percent of respondents used social media to learn about their child's diagnosis. Facebook (76%) and blogs (24%) were the most commonly accessed social media outlets, followed by Instagram (8%). Education about the diagnosis and treatment of cleft pathology (87%) was the most common reason for accessing social media, followed by companionship and support (56%), and advice about perioperative care (52%). Almost half (43%) of parents used social media to obtain information on their caregiver and treatment team, and 26% of parents used information gained on social media to guide their decision on where to seek care. Conclusion Social media is a readily available resource, one that will certainly shape the experiences of our patients and families for years to come.

  3. [A retrospective study of orthodontic treatment of children with clefts].

    Science.gov (United States)

    Brin, I; Bar-Abudi, R; Abed, Y; Ben-Bassat, Y; Harari, D; Zilberman, Y

    2003-04-01

    To evaluate the population of cleft patients treated in a Department of Orthodontics and the types of treatment modalities provided. Demographic, cleft related and treatment related data existing in the patients' files were supplemented by questionnaires. Comparisons were conducted among 3 cleft groups: cleft lip (CL), cleft lip and palate (CLP) and cleft palate (CP). The response rate was 36% (n = 152). The distribution of the patients in the 3 cleft groups, the sidedness, the male predominance and association with additional anomalies were similar to the reports in the literature. Most of the patients were the 3rd born (or more) and were of normal birth weight. Consanguity in the cleft families was at least 2.5 times more prevalent than that of the Israeli population and 30% reported on additional cleft in the family. Low birth weight and additional anomalies were found mainly in the CP group. Orthodontic involvement spanned 3 developmental periods: immediate postnatal presurgical treatment, phase I between the ages 6-8 years and full orthodontic treatment at a later age. Up to the age of 5 years only one lip operation was performed for 60% of the lip-affected children and one palate operation for 65% of the palate affected patients. 1. The distribution of the various cleft-related parameters in this retrospective study was similar to the findings in the literature. 2. The high prevalence of additional anomalies found emphasizes the need for a thorough examination of the cleft babies. 3. Orthodontic treatment was rendered in one and two phase protocols in addition to immediate postnatal pre-surgical intervention.

  4. Possible relationship between the stress-induced synaptic response and metaplasticity in the hippocampal CA1 field of freely moving rats.

    Science.gov (United States)

    Hirata, Riki; Matsumoto, Machiko; Judo, Chika; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro; Togashi, Hiroko

    2009-07-01

    Hippocampal long-term potentiation (LTP) is suppressed not only by stress paradigms but also by low frequency stimulation (LFS) prior to LTP-inducing high frequency stimulation (HFS; tetanus), termed metaplasticity. These synaptic responses are dependent on N-methyl-D-aspartate receptors, leading to speculations about the possible relationship between metaplasticity and stress-induced LTP impairment. However, the functional significance of metaplasticity has been unclear. The present study elucidated the electrophysiological and neurochemical profiles of metaplasticity in the hippocampal CA1 field, with a focus on the synaptic response induced by the emotional stress, contextual fear conditioning (CFC). The population spike amplitude in the CA1 field was decreased during exposure to CFC, and LTP induction was suppressed after CFC in conscious rats. The synaptic response induced by CFC was mimicked by LFS, i.e., LFS impaired the synaptic transmission and subsequent LTP. Plasma corticosterone levels were increased by both CFC and LFS. Extracellular levels of gamma-aminobutyric acid (GABA), but not glutamate, in the hippocampus increased during exposure to CFC or LFS. Furthermore, electrical stimulation of the medial prefrontal cortex (mPFC), which caused decreases in freezing behavior during exposure to CFC, counteracted the LTP impairment induced by LFS. These findings suggest that metaplasticity in the rat hippocampal CA1 field is related to the neural basis of stress experience-dependent fear memory, and that hippocampal synaptic response associated stress-related processes is under mPFC regulation.

  5. [Morphological classification and velopharyngeal function analysis of submucous cleft palate patients].

    Science.gov (United States)

    Heng, Yin; Chunli, Guo; Bing, Shi; Yang, Li; Jingtao, Li

    2016-10-01

    To enhance the accuracy in diagnosis and management of submucous cleft palate via a thorough analysis of its anatomical and functional details. Two hundred seventy-six submucous cleft palate cases from 2008 to 2014 were retrospectively investigated. Subgroup analysis were performed on the basis of preoperative velopharyngeal function, palatal morphology, cleft lip concurrence, and patient motives for treatment. Among the included cases, 96 (34.78%) were presented as velopharyngeal competence (VPC), 151 (54.71%) as velopharyngeal insufficiency (VPI), and 29 (10.51%) as marginal VPI (MVPI). Eighty cases (28.99%) also demonstrated cleft lip deformity, and 196 cases (71.01%) were merely submucous cleft palate. Compared with patients with submucous cleft palate only, those with cleft lips exhibited higher rates of complete velopharyngeal closure. The pathological spectrum of submucous cleft palate varied significantly. Only 103 (37.32%) cases met all the three diagnostic criteria proposed by Calnan. Given that the velopharyngeal closure rate varies among the subgroups, the factors analyzed in this study should be considered in the personalized manage-ment of submucous cleft palate.

  6. Prevalence and Characteristics of Developmental Dental Anomalies in Iranian Orofacial Cleft Patients.

    Science.gov (United States)

    Ajami, Shabnam; Pakshir, Hamidreza; Samady, Hedyeh

    2017-09-01

    Individuals with oral clefts exhibit considerably more dental anomalies than individuals without clefts. These problems could initially be among the symptoms of their disease and/or they may be the side effect of their treatments. Pushback palatoplasty could cause some interference during the development of teeth and result in tooth defects. The study was performed to assess the prevalence and characteristics of developmental dental anomalies in orofacial cleft patients who attended Shiraz Orthodontics Research Center-Cleft Lip and Palate Clinic. We managed to compare dental anomaly traits based on gender and cleft side. Eighty out of 121 cleft patients were included in this cross-sectional study. All the patients used pushback palatoplasty in their palate closure surgeries. Intraoral photographs, panoramic and intraoral radiographs, cone-beam computed tomography (CBCT) and dental and medical histories were examined and recorded by two observers. Data were analyzed using SPSS PC version 20.0. The differences in the side of cleft and dental anomalies were compared using the Mann-Whitney test. The mean age of patients was 14.27 years (SD=5.06). The most frequent cleft type was unilateral cleft lip and palate (50%) followed by bilateral cleft lip and palate (43.75%), cleft palate (2.5%) and cleft lip (1.25%). Male predominance (70%) was observed. 92.5 percent had at least one developmental dental anomaly. The most prevalent anomalies were hypodontia (71.25%) followed by microdontia (30%), root dilacerations (21.25%) and supernumerary teeth (15%). The most prevalent cleft types were unilateral and bilateral cleft lip and palate with male and left side predominance. Hypodontia, microdontia, dilacerations and supernumerary teeth were the most prevalent developmental dental anomalies among Iranian southwestern cleft patients. The surgical technique used to repair their cleft palate may have played a role in developmental dental defects.

  7. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H

    2015-01-01

    -500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP...... regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels...

  8. Isolation of Synaptosomes, Synaptic Plasma Membranes, and Synaptic Junctional Complexes.

    Science.gov (United States)

    Michaelis, Mary L; Jiang, Lei; Michaelis, Elias K

    2017-01-01

    Isolation of synaptic nerve terminals or synaptosomes provides an opportunity to study the process of neurotransmission at many levels and with a variety of approaches. For example, structural features of the synaptic terminals and the organelles within them, such as synaptic vesicles and mitochondria, have been elucidated with electron microscopy. The postsynaptic membranes are joined to the presynaptic "active zone" of transmitter release through cell adhesion molecules and remain attached throughout the isolation of synaptosomes. These "post synaptic densities" or "PSDs" contain the receptors for the transmitters released from the nerve terminals and can easily be seen with electron microscopy. Biochemical and cell biological studies with synaptosomes have revealed which proteins and lipids are most actively involved in synaptic release of neurotransmitters. The functional properties of the nerve terminals, such as responses to depolarization and the uptake or release of signaling molecules, have also been characterized through the use of fluorescent dyes, tagged transmitters, and transporter substrates. In addition, isolated synaptosomes can serve as the starting material for the isolation of relatively pure synaptic plasma membranes (SPMs) that are devoid of organelles from the internal environment of the nerve terminal, such as mitochondria and synaptic vesicles. The isolated SPMs can reseal and form vesicular structures in which transport of ions such as sodium and calcium, as well as solutes such as neurotransmitters can be studied. The PSDs also remain associated with the presynaptic membranes during isolation of SPM fractions, making it possible to isolate the synaptic junctional complexes (SJCs) devoid of the rest of the plasma membranes of the nerve terminals and postsynaptic membrane components. Isolated SJCs can be used to identify the proteins that constitute this highly specialized region of neurons. In this chapter, we describe the steps involved

  9. L-Type Voltage-Gated Ca2+ Channels Regulate Synaptic-Activity-Triggered Recycling Endosome Fusion in Neuronal Dendrites

    Directory of Open Access Journals (Sweden)

    Brian G. Hiester

    2017-11-01

    Full Text Available The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca2+ from distinct sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca2+ channels (L-VGCCs regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface. Accordingly, NMDA receptor activation triggered AMPA-type glutamate receptor trafficking to the dendritic surface in an L-VGCC-dependent manner. Conversely, potentiating L-VGCCs enhanced AMPA receptor surface expression only when NMDA receptors were also active. Thus L-VGCCs play a role in tuning activity-triggered surface expression of key synaptic proteins by gating the mode of RE fusion.

  10. Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum.

    Science.gov (United States)

    Rancillac, Armelle; Crépel, Francis

    2004-02-01

    Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long-term changes in synaptic efficacy. In the present study, we show that long-term potentiation (LTP) and long-term depression (LTD) were induced at these synapses by a low frequency stimulation protocol (2 Hz for 60 s) and that pairing this low frequency stimulation protocol with postsynaptic depolarization induced a marked shift of synaptic plasticity in favour of LTP. This LTP was cAMP independent, but required nitric oxide (NO) production from pre- and/or postsynaptic elements, depending on the stimulation or pairing protocol used, respectively. In contrast, LTD was not dependent on NO production but it required activation of postsynaptic group II and possibly of group I metabotropic glutamate receptors. Finally, stimulation of PFs at 8 Hz for 15 s also induced LTP at PF-SC synapses. But in this case, LTP was cAMP dependent, as was also observed at PF-PC synapses for presynaptic LTP induced in the same conditions. Thus, long-term changes in synaptic efficacy can be accomplished by PF-SCs synapses as well as by PF-PC synapses, suggesting that both types of plasticity might co-operate during cerebellar motor learning.

  11. Cervical vertebral maturation of female children with orofacial clefts.

    Science.gov (United States)

    Sun, Ling; Li, Wei Ran

    2013-09-01

    Objective : To evaluate the skeletal maturation of girls with orofacial clefts using the cervical vertebral maturation method. Design : Case-control study. Setting : The School of Stomatology, Peking University. Patients : A total of 173 girls with cleft lip and/or palate from 8 to 16 years old were compared with 1038 age-matched girls without clefts. Results : In the 8- to 9-year-olds, most of the girls from both groups were in cervical stage 1. In the 14- to 15-year-olds and 15- to 16-year-olds, almost all the girls from both groups were in cervical stages 5 and 6, and most of the 15- to 16-year-old girls were in cervical stage 6. Differences existed in each year for 9- to 14-year-olds, which was confirmed by statistical analysis. After ordinal logistical regression of data from girls 9 to 14 years of age, girls of the same age in the non-cleft lip and/or palate group were associated with 1.559 times the odds of having achieved higher cervical stages than those in the cleft lip and/or palate group. Most girls without cleft lip and/or palate were in cervical stages 3 and 4 in the 11- to 12-year-olds; whereas, it was not so obvious in the girls with cleft lip and/or palate. By the age of 12, girls with cleft lip and/or palate had 2.667 times the risk of delayed cervical stage 3, and the 95% confidence interval for the odds ratio was 1.013 to 7.019. Conclusions : Girls with cleft lip and/or palate are at a higher risk of delayed pubertal growth.

  12. Maternal Risk Factors for Oral Clefts: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Elham Mobasheri

    2011-01-01

    Full Text Available Introduction: A cleft lip with or without a cleft palate is one of the major congenital anomalies observed in newborns. This study explored the risk factors for oral clefts in Gorgan, Northern Iran.  Materials and Methods: This hospital-based case-control study was performed in three hospitals in Gorgan, Northern Iran between April 2006 and December 2009. The case group contained 33 newborns with oral clefts and the control group contained 63 healthy newborns. Clinical and demographic factors, including date of birth, gender of the newborns, type of oral cleft, consanguinity of the parents, parental ethnicity, and the mother's parity, age, education and intake of folic acid were recorded for analysis.  Results: A significant association was found between parity higher than 2 and the risk of an oral cleft (OR= 3.33, CI 95% [1.20, 9.19], P> 0.02. According to ethnicity, the odds ratio for oral clefts was 0.87 in Turkmens compared with Sistani people (CI 95% [0.25, 2.96] and 1.11 in native Fars people compared with Sistani people (CI 95% [0.38, 3.20]. A lack of folic acid consumption was associated with an increased risk of oral clefts but this was not statistically significant (OR = 1.42, CI 95% [0.58, 3.49]. There were no significant associations between sex (OR boy/girl = 0.96, CI 95% [0.41, 2.23], parent familial relations (OR = 1.07, CI 95% [0.43, 2.63], mother's age and oral clefts.  Conclusions:  The results of this study indicate that higher parity is significantly associated with an increased risk of an oral cleft, while Fars ethnicity and a low intake of folic acid increased the incidence of oral clefts but not significantly.

  13. Dental Care for a Child with Cleft Lip and Palate

    Science.gov (United States)

    ... Donor Spotlight Fundraising Ideas Vehicle Donation Volunteer Efforts Dental Care for a Child with Cleft Lip and ... submenu What We Do Cleft & Craniofacial Educational Materials Dental Care for a Child with Cleft Lip and ...

  14. First branchial cleft anomaly, a case for misdiagnosis.

    Science.gov (United States)

    Lanisnik, Bostjan; Didanovic, Vojko; Cizmarevic, Bogdan

    2004-01-01

    First branchial cleft anomaly is a rare condition that is often misdiagnosed and falsely mistreated before complete and definitive surgical treatment. Its origin is uncertain and the presence of ectodermal and sometimes also mesodermal elements has led some authors to the conclusion that it represents buried nests of cells forming the first branchial cleft and the underlying mesoderm. First branchial cleft anomaly can be presented as a cystic lesion, fistula or sinus extending towards the membranous external ear canal. The sinus tract runs through the parotid gland in close association with the facial nerve. There is no imaging method capable of identifying a first branchial cleft anomaly with certainty. The danger of facial nerve injury during surgery and the failure to identify the sinus tract running to the external ear canal are the main reasons for incomplete excision. The facial nerve must be identified and preserved and the lesion completely excised. Facial nerve injury is more common in attempts to remove recurrent branchial cleft lesions.

  15. An undescribed first branchial cleft anomaly.

    Science.gov (United States)

    Rockey, Jason Gabriel; John, D Gareth; Herbetko, John

    2003-06-01

    A variant of a type 2 first branchial cleft anomaly, in which accessory ossicles were found, is described. There follows a discussion of the classification of first branchial cleft abnormalities and how this particular case falls outside the standard classification. CT scanning is mentioned as the investigation that is most useful for defining these abnormalities.

  16. Secondary bone grafting for alveolar cleft in children with cleft lip or cleft lip and palate

    NARCIS (Netherlands)

    Guo, J.; Li, C.; Zhang, Q.; Wu, G.; Deacon, S.A.; Chen, J.; Hu, H.; Zou, S.; Ye, Q.

    2011-01-01

    BACKGROUND: Secondary alveolar bone grafting has been widely used to reconstruct alveolar cleft. However, there is still some controversy. OBJECTIVES: To compare the effectiveness and safety of different secondary bone grafting methods. SEARCH STRATEGY: The final electronic and handsearches were

  17. Variation among cleft centres in the use of secondary surgery for children with cleft palate: a retrospective cohort study

    Science.gov (United States)

    Sitzman, Thomas J; Hossain, Monir; Carle, Adam C; Heaton, Pamela C; Britto, Maria T

    2017-01-01

    Objectives To test whether cleft centres vary in their use of secondary cleft palate surgery, also known as revision palate surgery, and if so to identify modifiable hospital factors and surgeon factors that are associated with use of secondary surgery. Design Retrospective cohort study. Setting Forty-three paediatric hospitals across the USA. Patients Children with cleft lip and palate who underwent primary cleft palate repair from 1999 to 2013. Main outcome measures Time from primary cleft palate repair to secondary palate surgery. Results We identified 4939 children who underwent primary cleft palate repair. At 10 years after primary palate repair, 44% of children had undergone secondary palate surgery. Significant variation existed among hospitals (ppalate repair before 9 months of age was associated with an increased hazard of secondary palate surgery (initial HR 6.74, 95% CI 5.30 to 8.73). Postoperative antibiotics, surgeon procedure volume and hospital procedure volume were not associated with time to secondary surgery (p>0.05). Of the outcome variation attributable to hospitals and surgeons, between-hospital differences accounted for 59% (ppalate surgery exists depending on a child’s age at primary palate repair and the hospital and surgeon performing their repair. Performing primary palate repair before 9 months of age substantially increases the hazard of secondary surgery. Further research is needed to identify other factors contributing to variation in palate surgery outcomes among hospitals and surgeons. PMID:29479567

  18. First branchial cleft anomalies: otologic manifestations and treatment outcomes.

    Science.gov (United States)

    Shinn, Justin R; Purcell, Patricia L; Horn, David L; Sie, Kathleen C Y; Manning, Scott C

    2015-03-01

    This study describes the presentation of first branchial cleft anomalies and compares outcomes of first branchial cleft with other branchial cleft anomalies with attention to otologic findings. Case series with chart review. Pediatric tertiary care facility. Surgical databases were queried to identify children with branchial cleft anomalies. Descriptive analysis defined sample characteristics. Risk estimates were calculated using Fisher's exact test. Queries identified 126 subjects: 27 (21.4%) had first branchial cleft anomalies, 80 (63.4%) had second, and 19 (15.1%) had third or fourth. Children with first anomalies often presented with otologic complications, including otorrhea (22.2%), otitis media (25.9%), and cholesteatoma (14.8%). Of 80 children with second branchial cleft anomalies, only 3 (3.8%) had otitis. Compared with children with second anomalies, children with first anomalies had a greater risk of requiring primary incision and drainage: 16 (59.3%) vs 2 (2.5%) (relative risk [RR], 3.5; 95% confidence interval [CI], 2.4-5; Pbranchial cleft anomalies often present with otologic complaints. They are at increased risk of persistent disease, particularly if anomalies lie medial to the facial nerve. They may require ear-specific surgery such as tympanoplasty. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  19. Cleft lip and palate: series of unusual clinical cases.

    Science.gov (United States)

    Paranaíba, Lívia Máris Ribeiro; Miranda, Roseli Teixeira de; Martelli, Daniella Reis Barbosa; Bonan, Paulo Rogério Ferreti; Almeida, Hudson de; Orsi Júnior, Julian Miranda; Martelli Júnior, Hercílio

    2010-01-01

    Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face, corresponding to approximately 65% of all malformations of the craniofacial region. to describe unusual clinical cases of non-syndromic CL/P (CL/PNS), diagnosed in a reference service in Minas Gerais, Brazil, and correlate these alterations with possible risk factors. we carried out a retrospective study, between the years of 1992 and the 1st half of 2009, from medical records. Among the 778 cases of CL/PNS diagnosed in the period of 17 years, 5 (0.64%) were unusual CL/PNS, and all patients were male. It was found that among the 5 patients, 2 had incomplete right cleft lip with incomplete cleft palate, 2 were affected by left incomplete cleft lip and incomplete cleft palate, and 1 had a cleft lip and palate associated with complete right cleft palate. Risk factors such as consanguinity, maternal smoking and alcohol consumption, medication usage during pregnancy, history of abortion and/or stillbirths and maternal diseases were not associated with unusual CL/PNS. This study described 5 unusual cases of CL/PNS in a Brazilian population; no associations with the risk factors analyzed were seen. It also confirmed the unusualness of the prevalence of such alterations.

  20. Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

    Directory of Open Access Journals (Sweden)

    Aisa N. Chepkova

    2015-01-01

    Full Text Available Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old to old (18–24 months of age animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age. Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

  1. Presurgical nasoalveolar moulding in unilateral cleft lip and palate

    Directory of Open Access Journals (Sweden)

    Mohammed Zuhaib

    2016-01-01

    Full Text Available Context: Presurgical nasoalveolar moulding (PNAM is a non-surgical method of reshaping the cleft lip, alveolus, palate and the nose to minimize the severity of the cleft deformity, before primary cheiloplastyand palatoplasty. In this context, PNAM proves to be an invaluable asset in the management of unilateral cleft lip and palate. Aims: The study was conducted to evaluate the effi cacy of PNAM in the management of unilateral cleft lip and palate with the following objectives: (1 To assess and compare the degree of reduction in the size of cleft palate and alveolus (pre-PNAM and post-PNAM. (2 To evaluate and compare the improvement in columellar length and correction of columellar deviation (pre-PNAM and post-PNAM. (3 To assess the changes in the position of the alar base and the alar cartilages. Settings and Design: Prospective study. Subjects and Methods: A prospective study consisting of, which included 20 patients with complete unilateral cleft lip and palate was conducted. The age at the start of PNAM treatment of the infants ranged from 2 to 44 days of age reporting to our institute between December 2011 and August 2013. All the patients underwent PNAM therapy before primary cheiloplasty at 6 months of age; clinical parameters were assessed pre- and post-therapy using photographs and dental study models of the maxilla. Statistical Analysis Used: Student's t-test for paired comparisons. Results: Results of the study showed a promising reduction in the cleft size before the surgery, signifi cant improvement in nasal symmetry, including the columellar length on the cleft side. Conclusions: PNAM is a valuable adjunct to our surgical armamentarium in dealing with the challenges of primary closure of unilateral cleft lip and palate thereby enhancing the overall surgical outcome. The advantages of this method include the simplicity of the procedure and improving the quality of surgical repair, particularly in obtaining tension free muscle

  2. Morphological evaluation of clefts of the lip, palate, or both in dogs.

    Science.gov (United States)

    Peralta, Santiago; Fiani, Nadine; Kan-Rohrer, Kimi H; Verstraete, Frank J M

    2017-08-01

    OBJECTIVE To systematically characterize the morphology of cleft lip, cleft palate, and cleft lip and palate in dogs. ANIMALS 32 client-owned dogs with clefts of the lip (n = 5), palate (23), or both (4) that had undergone a CT or cone-beam CT scan of the head prior to any surgical procedures involving the oral cavity or face. PROCEDURES Dog signalment and skull type were recorded. The anatomic form of each defect was characterized by use of a widely used human oral-cleft classification system on the basis of CT findings and clinical images. Other defect morphological features, including shape, relative size, facial symmetry, and vomer involvement, were also recorded. RESULTS 9 anatomic forms of cleft were identified. Two anatomic forms were identified in the 23 dogs with cleft palate, in which differences in defect shape and size as well as vomer abnormalities were also evident. Seven anatomic forms were observed in 9 dogs with cleft lip or cleft lip and palate, and most of these dogs had incisive bone abnormalities and facial asymmetry. CONCLUSIONS AND CLINICAL RELEVANCE The morphological features of congenitally acquired cleft lip, cleft palate, and cleft lip and palate were complex and varied among dogs. The features identified here may be useful for surgical planning, developing of clinical coding schemes, or informing genetic, embryological, or clinical research into birth defects in dogs and other species.

  3. Maxillary arch width in unoperated adult bilateral cleft lip and alveolus and complete bilateral cleft lip and palate.

    NARCIS (Netherlands)

    Latief, B.S.; Lekkas, C.; Kuijpers, M.A.R.

    2010-01-01

    OBJECTIVES: To study maxillary arch width in adult patients with bilateral cleft lip and alveolus (BCLA) or with complete bilateral cleft lip and palate (BCLP), who have not had any surgery. SETTING AND SAMPLING POPULATION: Eighteen patients with BCLA, 13 patients with BCLP, and 24 controls from

  4. Cross-linguistic perspectives on speech assessment in cleft palate

    DEFF Research Database (Denmark)

    Willadsen, Elisabeth; Henningsson, Gunilla

    2012-01-01

    . Finally, the influence of different languages on some aspects of language acquisition in young children with cleft palate is presented and discussed. Until recently, not much has been written about cross linguistic perspectives when dealing with cleft palate speech. Most literature about assessment......This chapter deals with cross linguistic perspectives that need to be taken into account when comparing speech assessment and speech outcome obtained from cleft palate speakers of different languages. Firstly, an overview of consonants and vowels vulnerable to the cleft condition is presented. Then......, consequences for assessment of cleft palate speech by native versus non-native speakers of a language are discussed, as well as the use of phonemic versus phonetic transcription in cross linguistic studies. Specific recommendations for the construction of speech samples in cross linguistic studies are given...

  5. The glutamate/GABA-glutamine cycle

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2006-01-01

    Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate...... or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism...... of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must...

  6. An unusual presentation of presentation of a branchial cleft cyst.

    Science.gov (United States)

    Vemula, Rahul; Greco, Gregory

    2012-05-01

    Branchial cleft cysts are congenital anomalies that arise from the aberrant embryological development of the branchial apparatus. The location of a branchial cleft cyst is determined by which branchial cleft failed to obliterate during embryological development, with the second branchial cleft cyst being the most commonly recognized lesion. Although the most common location for branchial cleft cysts is between the external auditory canal and the level of the clavicle, the literature does describe unusual locations. We present a case a 15-year-old boy who had an enlarging lesion on his back that had been present since birth. A presumptive radiologic diagnosis of lymphangioma circumscriptum was made. Upon excision of the lesion and pathologic examination, it was determined to be a branchial cleft cyst. The patient had an uneventful postoperative course, and no recurrence was noted after a 2-year follow-up. Our clinical report demonstrates a lesion on the posterior thorax that proved to be a branchial cleft cyst and should always be part of the differential diagnosis for soft tissue masses of the thorax.

  7. Dental anomalies in different cleft groups related to neural crest developmental fields contributes to the understanding of cleft aetiology

    DEFF Research Database (Denmark)

    Riis, Louise Claudius; Kjær, Inger; Mølsted, Kirsten

    2014-01-01

    OBJECTIVE: To analyze dental deviations in three cleft groups and relate findings to embryological neural crest fields (frontonasal, maxillary, and palatal). The overall purpose was to evaluate how fields are involved in different cleft types. DESIGN: Retrospective audit of clinical photographs...

  8. Oral clefting in china over the last decade: 205,679 patients.

    Science.gov (United States)

    Kling, Rochelle R; Taub, Peter J; Ye, Xiaoqian; Jabs, Ethylin Wang

    2014-10-01

    China is the most populated country and has one of the highest prevalences of oral clefting. The present study reports the epidemiology and surgical procedures performed on the largest reported cohort of individuals with clefting in China. A retrospective review of patients who received cleft repair through Smile Train in China from 2000 to 2011 was conducted. Data on demographics, cleft characteristics, associated malformations, pregnancy and family history, and surgical technique were analyzed using SPSS (IBM, Chicago, Ill.). A total of 205,679 patients underwent 209,169 cleft procedures. Cleft lip and palate (42.7%) was most common followed by isolated cleft palate (32.4%) and isolated cleft lip (24.9%). Males accounted for 63.5% of cases. The average age at initial surgery was 6.12 years. By 2011, this decreased to 1.8 years of age for lip repair and to 5.9 years of age for palate repair. The preferred techniques were rotation-advancement (55%) for unilateral lip repair and Von-Langenbeck (38%) and pushback (39%) for palate repair. The percentages of cases with associated anomalies and surgical complications were 12.8% and 0.36%, respectively. This study provides insight into cleft care in China as it reports the largest cohort of cleft patients treated by surgeons to date. Our results generally follow trends previously reported in China and developed countries. The male:female ratio for cleft palate patients was higher than expected. The average age at primary repair is higher than recommended, but seems to be decreasing.

  9. The characteristics and distribution of dental anomalies in patients with cleft.

    Science.gov (United States)

    Wu, Ting-Ting; Chen, Philip K T; Lo, Lun-Jou; Cheng, Min-Chi; Ko, Ellen Wen-Ching

    2011-01-01

    Dental anomalies associated with different severities of cleft lip and palate have been rarely reported. This retrospective study investigates the characteristics of dental anomalies associated with different types of cleft, and compares the dental anomaly traits based on sex and severity of cleft. Cleft patients born in 1995 with qualified diagnostic records from 7 to 11 years were included for evaluation. Records were retrieved from database of Chang Gung Craniofacial Center, including panoramic radiographs and intraoral photographs. In total, 196 patients with complete records were included in the evaluation. This study compares the dental anomalies associated with each type of cleft. The frequency of dental anomalies in the maxillary incisor area in the cleft palate (CP) group (20%) was significantly lower than that in other groups. The frequency of missing maxillary lateral incisors (MLIs) increased as the cleft severity increased. Supernumerary teeth and missing lower incisors exhibited the opposite trend. No sexual dimorphism appeared in terms of the frequencies of peg laterals and missing MLIs. The distribution patterns of missing MLIs and peg laterals in males, but not in females, were consistent for the three types of unilateral clefts. Regarding the characteristics of dental anomalies among the three unilateral clefts, missing MLIs, supernumerary teeth, and missing lower incisors were found to be related to cleft severity. The maxillary lateral incisor was the most affected tooth in the cleft area. The frequency of missing MLIs and peg laterals was not sexual dimorphic, but the distribution pattern was different between the sexes.

  10. Incidence of bifid uvula and its relationship to submucous cleft palate and a family history of oral cleft in the Brazilian population.

    Science.gov (United States)

    Sales, Sizina Aguiar G; Santos, Maria Luiza; Machado, Renato Assis; Dias, Verônica Oliveira; Nascimento, Jairo Evangelista; Swerts, Mario Sérgio Oliveira; Júnior, Hercílio Martelli; Martelli, Daniella Reis Barbosa

    2017-08-24

    Bifid uvula is a frequently observed anomaly in the general population and can be regarded as a marker for submucous cleft palate. In this study aimed to determine the frequency of bifid uvula and submucous cleft palate and their relationship with oral clefts in a Brazilian population. We conducted a transversal, descriptive and quantitative study of 1206 children between August 2014 and December 2015. A clinical examination of the children was conducted by means of inspection of the oral cavity with the aid of a tongue depressor and directed light. After the clinical examination in children, parents answered a questionnaire with questions about basic demographic information and their family history of oral clefts in their first-degree relatives. After application of the questionnaires, the information collected was archived in a database and analyzed by the statistical program SPSS ® version 19.0, by applying Chi-Square tests. Values with previews, with broader and diverse populations, seeking to associate the occurrence of bifid uvula, submucous cleft palate and oral clefts. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. Mothers' experiences when their infants were diagnosed with cleft ...

    African Journals Online (AJOL)

    Traditionally the diagnosis of cleft lip and palate was made at birth or soon thereafter, but modern technology has led to the identification of cleft lip prenatally. The aim of this study was to describe 16 mothers' experiences of pre- and postnatal diagnosis of their infants' cleft lip and palate, and to develop clinical guidelines for ...

  12. Smile Train: The ascendancy of cleft care in India

    Directory of Open Access Journals (Sweden)

    Singh Subodh

    2009-10-01

    Full Text Available Though India has an estimated population of one million untreated cleft patients, facilities for its treatment have been limited and are not evenly distributed across the country. Furthermore, a paucity of committed cleft surgeons in fewer hospitals to provide quality surgical treatment to these patients, poverty, illiteracy, superstitions and poor connectivity in some remote regions severely limit the chances of an average cleft lip patient born in India from receiving rational and effective comprehensive treatment for his/her malady. The Smile Train Project with its singular focus on cleft patients started its philanthropic activities in India in the year 2000. It made hospitals and included clefts surgeon equal partners in this programme and helped them treat as many cleft patients as they possibly could. The Project encouraged improvement of the training and infrastructure in various centres across the length and breadth of the region. The Project received an unprecedented success in terms of growth of number of centres, cleft surgeons and quantum of cleft patients reporting for treatment. The G S Memorial Hospital is one such partner hospital. It started innovative outreach programmes and took a holistic view of the needs of these patients and their families. With the support of the Smile Train, it has not only succeeded in providing treatment to more than 14,500 patients in 5 years, but has also devised innovative outreach programmes and seamlessly incorporated salient changes in the hospital system to suit the needs of the target population.

  13. Crystal structure of Arabidopsis thaliana Dawdle forkhead-associated domain reveals a conserved phospho-threonine recognition cleft for dicer-like 1 binding.

    Science.gov (United States)

    Machida, Satoru; Yuan, Y Adam

    2013-07-01

    Dawdle (DDL) is a microRNA processing protein essential for the development of Arabidopsis. DDL contains a putative nuclear localization signal at its amino-terminus and forkhead-associated (FHA) domain at the carboxyl-terminus. Here, we report the crystal structure of the FHA domain of Arabidopsis Dawdle, determined by multiple-wavelength anomalous dispersion method at 1.7-Å resolution. DDL FHA structure displays a seven-stranded β-sandwich architecture that contains a unique structural motif comprising two long anti-parallel strands. Strikingly, crystal packing of the DDL FHA domain reveals that a glutamate residue from the symmetry-related DDL FHA domain, a structural mimic of the phospho-threonine, is specifically recognized by the structurally conserved phospho-threonine binding cleft. Consistently with the structural observations, co-immuno-precipitation experiments performed in Nicotiana benthamiana show that the DDL FHA domain co-immuno-precipitates with DCL1 fragments containing the predicted pThr+3(Ile/Val/Leu/Asp) motif. Taken together, we count the recognition of the target residue by the canonical binding cleft of the DDL FHA domain as the key molecular event to instate FHA domain-mediated protein-protein interaction in plant miRNA processing.

  14. Craniofacial morphology in complete unilateral cleft lip and palate patients consecutively treated with 1-stage repair of the cleft.

    NARCIS (Netherlands)

    Fudalej, P.S.; Surowiec, Z.; Offert, B.; Dudkiewicz, Z.; Katsaros, C.

    2010-01-01

    OBJECTIVE: To retrospectively evaluate the craniofacial morphology of children with a complete unilateral cleft lip and palate treated with a 1-stage simultaneous cleft repair performed in the first year of life. METHODS: Cephalograms and extraoral profile photographs of 61 consecutively treated

  15. Type II first branchial cleft anomaly.

    Science.gov (United States)

    Al-Mahdi, Akmam H; Al-Khurri, Luay E; Atto, Ghada Z; Dhaher, Ameer

    2013-01-01

    First branchial cleft anomaly is a rare disease of the head and neck. It accounts for less than 8% of all branchial abnormalities. It is classified into type I, which is thought to arise from the duplication of the membranous external ear canal and are composed of ectoderm only, and type II that have ectoderm and mesoderm. Because of its rarity, first branchial cleft anomaly is often misdiagnosed and results in inappropriate management. A 9-year-old girl presented to us with fistula in the submandibular region and discharge in the external ear. Under general anesthesia, complete surgical excision of the fistula tract was done through step-ladder approach, and the histopathologic examination confirmed the diagnosis of type II first branchial cleft anomaly.

  16. Dental anomalies associated with cleft lip and palate in Northern Finland.

    Science.gov (United States)

    Lehtonen, V; Anttonen, V; Ylikontiola, L P; Koskinen, S; Pesonen, P; Sándor, G K

    2015-12-01

    Despite the reported occurrence of dental anomalies of cleft lip and palate, little is known about their prevalence in children from Northern Finland with cleft lip and palate. The aim was to investigate the prevalence of dental anomalies among patients with different types of clefts in Northern Finland. Design and Statistics: patient records of 139 subjects aged three years and older (with clefts treated in Oulu University Hospital, Finland during the period 1996-2010 (total n. 183) were analysed for dental anomalies including the number of teeth, morphological and developmental anomalies and their association with the cleft type. The analyses were carried out using Chi-square test and Fisher's exact test. Differences between the groups were considered statistically significant at p values dental anomaly was detected in 47% of the study population. Almost one in three (26.6%) subjects had at least one anomaly and 17.9% had two or three anomalies. The most common type of anomaly in permanent teeth were missing teeth followed by supernumerary teeth. Supernumerary teeth were significantly more apparent when the lip was involved in the cleft compared with palatal clefts. Missing teeth were less prevalent among those 5 years or younger. The prevalence of different anomalies was significantly associated with the cleft type in both age groups. Dental anomalies are more prevalent among cleft children than in the general population in Finland. The most prevalent anomalies associated with cleft were missing and supernumerary teeth.

  17. Growth hormone deficiency in cleft lip and palate patients

    Directory of Open Access Journals (Sweden)

    Shahin AbdollahiFakhim

    2015-11-01

    Full Text Available Introduction: Failure to thrive (FTT is relatively common among cleft patients, most commonly attributed to feeding problems during the first months of life. Close association between midline clefts and pituitary gland abnormalities prompted us to determine the frequency of growth hormone deficiency in cleft patients, which is easily treated. Methods: Any cleft patient with FTT was studied and when the patient’s height was under the 3rd percentile of normal, growth hormone was checked after clonidine administration. Growth hormone was checked before and 30, 60 and 90 minutes after clonidine use. Results: Of 670 patients with cleft lip or palate, 31 patients (4% had some kind of growth retardation according to weight, height or head circumstance. Eighteen patients were under the 3rd percentile of normal height. Growth hormone deficiency was detected in 8 patients out of 18 patients and overall frequency of growth hormone deficiency among cleft patients with growth retardation was 25.8% (8 out of 31. Seven patients of 8 were male whereas one was female and half of the patients were syndromic. Conclusion: Cleft patients have many problems with normal feeding and all kind of support should be provided to achieve near-normal feeding and they should be monitored for normal growth. Any patient with growth retardation, especially height decrease, should be assessed for growth hormone deficiency.

  18. Possible contributions of a novel form of synaptic plasticity in Aplysia to reward, memory, and their dysfunctions in mammalian brain.

    Science.gov (United States)

    Hawkins, Robert D

    2013-09-18

    Recent studies in Aplysia have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in mammals, where it may contribute to reward, memory, and their dysfunctions in several psychiatric disorders. In Aplysia, spontaneous release is enhanced by activation of presynaptic serotonin receptors, but presynaptic D1 dopamine receptors or nicotinic acetylcholine receptors could play a similar role in mammals. Those receptors enhance spontaneous release of glutamate in hippocampus, entorhinal cortex, prefrontal cortex, ventral tegmental area, and nucleus accumbens. In all of those brain areas, glutamate can activate postsynaptic receptors to elevate Ca(2+) and engage mechanisms of early-phase long-term potentiation (LTP), including AMPA receptor insertion, and of late-phase LTP, including protein synthesis and growth. Thus, presynaptic receptors and spontaneous release may contribute to postsynaptic mechanisms of plasticity in brain regions involved in reward and memory, and could play roles in disorders that affect plasticity in those regions, including addiction, Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

  19. Risk factors and comorbidities in Brazilian patients with orofacial clefts

    Directory of Open Access Journals (Sweden)

    Heglayne Pereira Vital da Silva

    2018-04-01

    Full Text Available Abstract: Considering that environmental risk factors substantially contribute to the etiology of orofacial clefts and that knowledge about the characteristics and comorbidities associated with oral clefts is fundamental to promoting better quality of life, this study aimed to describe the risk factors, main characteristics, and comorbidities of a group of patients with cleft lip and/or cleft palate (CL/P from Rio Grande do Norte (RN, Brazil. Data were obtained from 173 patients with CL/P using a form from the Brazilian database on Orofacial Clefts. Most patients were male with cleft lip and palate and had a normal size and weight at birth; presented few neonatal intercurrent events; and had anemia and respiratory and cardiovascular diseases as main associated comorbidities. They also required timely surgical rehabilitation and multidisciplinary care to stimulate their neuropsychomotor development. In addition, a high frequency of familial recurrence and of parental consanguinity was evidenced in the studied population, especially for the cleft lip and cleft palate type. Other relevant findings were the considerable maternal exposure to alcohol, infections, smoking, and hypertension, as well as low supplementation with vitamins and minerals and deliberate consumption of analgesics, antibiotics, and antihypertensives during pregnancy. Characterization of the CL/P patient profile is essential for the planning of health services and integration among the health professionals involved in the diagnosis and treatment of these malformations. Our results reinforce the need for additional research to confirm the association between environmental factors and the development of orofacial clefts.

  20. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

    Science.gov (United States)

    Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

    2016-02-01

    The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated

  1. Maxillary growth in a congenital cleft palate canine model for surgical research.

    Science.gov (United States)

    Paradas-Lara, Irene; Casado-Gómez, Inmaculada; Martín, Conchita; Martínez-Sanz, Elena; López-Gordillo, Yamila; González, Pablo; Rodríguez-Bobada, Cruz; Chamorro, Manuel; Arias, Pablo; Maldonado, Estela; Ortega, Ricardo; Berenguer, Beatriz; Martínez-Álvarez, Concepción

    2014-01-01

    We have recently presented the Old Spanish Pointer dog, with a 15-20% spontaneous congenital cleft palate rate, as a unique experimental model of this disease. This study aimed to describe the cleft palate of these dogs for surgical research purposes and to determine whether congenital cleft palate influences maxillofacial growth. Seven newborn Old Spanish Pointer dogs of both sexes, comprising a cleft palate group (n = 4) and a normal palate group (n = 3), were fed using the same technique. Macroscopic photographs and plaster casts from the palate, lateral radiographs and computer tomograms of the skull were taken sequentially over 41 weeks, starting at week 5. The cleft morphology, the size and the tissue characteristics in these dogs resembled the human cleft better than current available animal models. During growth, the cleft width varies. Most of the transverse and longitudinal measures of the palate were statistically lower in the cleft palate group. The cleft palate group showed hypoplasia of the naso-maxillary complex. This model of congenital cleft palate seems suitable for surgical research purposes. A reduced maxillofacial pre- and post-natal development is associated to the congenital cleft palate in the Old Spanish Pointer dog. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  2. Cleft lip and palate: recommendations for dental anesthetic procedure based on anatomic evidences

    Directory of Open Access Journals (Sweden)

    Ivy Kiemle Trindade-Suedam

    2012-02-01

    Full Text Available Patients with cleft lip and palate usually present dental anomalies of number, shape, structure and position in the cleft area and the general dentist is frequently asked to restore or extract those teeth. Considering that several anatomic variations are expected in teeth adjacent to cleft areas and that knowledge of these variations by general dentists is required for optimal treatment, the objectives of this paper are: 1 to describe changes in the innervation pattern of anterior teeth and soft tissue caused by the presence of a cleft, 2 to describe a local anesthetic procedure in unilateral and bilateral clefts, and 3 to provide recommendations to improve anesthetic procedures in patients with cleft lip and palate. The cases of 2 patients are presented: one with complete unilateral cleft lip and palate, and the other with complete bilateral cleft lip and palate. The patients underwent local anesthesia in the cleft area in order to extract teeth with poor bone support. The modified anesthetic procedure, respecting the altered course of nerves in the cleft maxilla and soft tissue alterations at the cleft site, was accomplished successfully and the tooth extraction was performed with no pain to the patients. General dentists should be aware of the anatomic variations in nerve courses in the cleft area to offer high quality treatment to patients with cleft lip and palate.

  3. Maternal occupational risk factors for oral clefts

    NARCIS (Netherlands)

    Lorente, C; Cordier, S; Bergeret, A; De Walle, HEK; Goujard, J; Ayme, S; Knill-Jones, R; Calzolari, E

    Objectives This study investigated the role of maternal exposures at work during pregnancy in the occurrence of oral clefts. Methods The occupational exposures of 851 women (100 mothers of babies with oral clefts and 751 mothers of healthy referents) who worked during the first trimester of

  4. GABA regulates synaptic integration of newly generated neurons in the adult brain

    Science.gov (United States)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  5. Primary unilateral cleft lip repair

    OpenAIRE

    Adenwalla, H. S.; Narayanan, P. V.

    2009-01-01

    The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform clos...

  6. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Bo [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China); Zhang, Shu [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Lang, Qiaolin [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Song, Jianxia; Han, Lihui [Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Liu, Aihua, E-mail: liuah@qibebt.ac.cn [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China)

    2015-07-16

    Highlights: • E. coli surface-dispalyed Gldh exhibiting excellent enzyme activity and stability. • Sensitive amperometric biosensor for glutamate using Gldh-bacteria and MWNTs. • The glutamate biosensor exhibited high specificity and stability. - Abstract: A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP{sup +}-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP{sup +} involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current–time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM–1 mM and 2–10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N = 3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection.

  7. Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus.

    Science.gov (United States)

    Xie, Meilan; Yan, Jie; He, Chao; Yang, Li; Tan, Gang; Li, Chao; Hu, Zhian; Wang, Jiali

    2015-06-01

    Hippocampus-dependent learning memory is sensitive to sleep deprivation (SD). Although the ionotropic glutamate receptors play a vital role in synaptic plasticity and learning and memory, however, whether the expression of these receptor subunits is modulated by sleep loss remains unclear. In the present study, western blotting was performed by probing with specific antibodies against the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1, GluA2, GluA3, and against the N-methyl-d-aspartate (NMDA) glutamate receptor subunits GluN1, GluN2A, GluN2B. In hippocampus, down regulation of surface GluA1 and GluN2A surface expression were observed in both SD groups. However, surface expression level of GluA2, GluA3, GluN1 and GluN2B was significantly up-regulated in 8h-SD rats when compared to the 4h-SD rats. In parallel with the complex changes in AMPA and NMDA receptor subunit expressions, we found the 8h-SD impaired rat spatial working memory in 30-s-delay T-maze task, whereas no impairment of spatial learning was observed in 4h-SD rats. These results indicate that sleep loss alters the relative expression levels of the AMPA and NMDA receptors, thus affects the synaptic strength and capacity for plasticity and partially contributes to spatial memory impairment. Copyright © 2015. Published by Elsevier B.V.

  8. Reward memory relieves anxiety-related behavior through synaptic strengthening and protein kinase C in dentate gyrus.

    Science.gov (United States)

    Lei, Zhuofan; Liu, Bei; Wang, Jin-Hui

    2016-04-01

    Anxiety disorders are presumably associated with negative memory. Psychological therapies are widely used to treat this mental deficit in human beings based on the view that positive memory competes with negative memory and relieves anxiety status. Cellular and molecular processes underlying psychological therapies remain elusive. Therefore, we have investigated its mechanisms based on a mouse model in which food reward at one open-arm of the elevated plus-maze was used for training mice to form reward memory and challenge the open arms. Mice with the reward training showed increased entries and stay time in reward open-arm versus neutral open-arm as well as in open-arms versus closed-arms. Accompanying with reward memory formation and anxiety relief, glutamatergic synaptic transmission in dentate gyrus in vivo and dendritic spines in granule cells became upregulated. This synaptic up-regulation was accompanied by the expression of more protein kinase C (PKC) in the dendritic spines. The inhibition of PKC by chelerythrine impaired the formation of reward memory, the relief of anxiety-related behavior and the up-regulation of glutamate synapses. Our results suggest that reward-induced positive memory relieves mouse anxiety-related behavior by strengthening synaptic efficacy and PKC in the hippocampus, which imply the underlying cellular and molecular processes involved in the beneficial effects of psychological therapies treating anxiety disorders. © 2015 Wiley Periodicals, Inc.

  9. Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, Silvarosa; Frondaroli, Adele; Dieni, Cristina; Dutia, Mayank B; Pettorossi, Vito E

    2007-07-01

    In rat brainstem slices, we investigated the influence of the neurosteroids tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with gamma-aminobutyric acid (GABA) and glutamate receptors was analysed by using specific antagonists for GABA(A) (bicuculline), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate [2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide disodium salt (NBQX)], N-methyl-D-aspartate (NMDA) [D-(-)-2-amino-5-phosphonopentanoic acid (AP-5)] and group I metabotropic glutamate receptors (mGlu-I) [(R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA)] receptors. THDOC and ALLO evoked two opposite long-lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after neurosteroid application. The depressions depended on GABA(A) receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, as NBQX markedly reduced the incidence of early firing rate enhancement and, in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABA(A) inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABA(A) receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABA(A) and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal

  10. Genetic survey of a group of children with clefting: implications for genetic counseling

    NARCIS (Netherlands)

    Hofstee, Y.; Kors, N.; Hennekam, R. C.

    1993-01-01

    A cleft lip, cleft palate, or both are associated with a high frequency of other anomalies. This study gives an inventory of associated anomalies in a consecutive group of children (n = 36) with clefts, referred to a local multidisciplinary cleft team in the Netherlands. In 47.2% of cleft patients

  11. Synaptic electronics: materials, devices and applications.

    Science.gov (United States)

    Kuzum, Duygu; Yu, Shimeng; Wong, H-S Philip

    2013-09-27

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented.

  12. Synaptic electronics: materials, devices and applications

    International Nuclear Information System (INIS)

    Kuzum, Duygu; Yu, Shimeng; Philip Wong, H-S

    2013-01-01

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented. (topical review)

  13. Presurgical Nasal Molding With a Nasal Spring in Patients With Mild-to-Moderate Nasal Deformity With Incomplete Unilateral Cleft Lip With or Without Cleft Palate.

    Science.gov (United States)

    Peanchitlertkajorn, Supakit

    2018-01-01

    Traditional nasoalveolar molding (NAM) requires steep learning curve for clinicians and significant compliance from parents. Nasal springs have been developed by the author to simplify presurgical nasal molding. This article presents the design, construction, and application of the spring. The treatment goal is to improve nasal deformity prior to primary repair in infants born with incomplete unilateral cleft lip with or without cleft palate. The design, fabrication, and utility of the nasal spring are described. The spring has a simpler design and construction compared to a traditional NAM appliance. Two patients with incomplete unilateral cleft lip with and without cleft palate are presented. The spring is constructed and delivered. The active arm of the spring can be 3-dimensionally (3-D) adjusted to mold the alar cartilage of the affected nostril. The spring does not require an oral plate for adherence as a traditional NAM appliance does, hence an oral impression is not needed. The spring is easy for clinicians to adjust. It also requires less compliance by parents. Main Outcome Measures/Results: The presurgical molding achieved by the use of a nasal spring improved surgical nasolabial aesthetic outcomes. The nasal springs are effective in reducing the initial cleft nasal deformity. This facilitates primary surgical cleft lip and nose correction and improves surgical outcomes in patients with incomplete unilateral cleft lip with or without cleft palate.

  14. [Surgical correction of cleft palate].

    Science.gov (United States)

    Kimura, F T; Pavia Noble, A; Soriano Padilla, F; Soto Miranda, A; Medellín Rodríguez, A

    1990-04-01

    This study presents a statistical review of corrective surgery for cleft palate, based on cases treated at the maxillo-facial surgery units of the Pediatrics Hospital of the Centro Médico Nacional and at Centro Médico La Raza of the National Institute of Social Security of Mexico, over a five-year period. Interdisciplinary management as performed at the Cleft-Palate Clinic, in an integrated approach involving specialists in maxillo-facial surgery, maxillar orthopedics, genetics, social work and mental hygiene, pursuing to reestablish the stomatological and psychological functions of children afflicted by cleft palate, is amply described. The frequency and classification of the various techniques practiced in that service are described, as well as surgical statistics for 188 patients, which include a total of 256 palate surgeries performed from March 1984 to March 1989, applying three different techniques and proposing a combination of them in a single surgical time, in order to avoid complementary surgery.

  15. Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.

    Science.gov (United States)

    Gowans, Lord Jephthah Joojo; Oseni, Ganiyu; Mossey, Peter A; Adeyemo, Wasiu Lanre; Eshete, Mekonen A; Busch, Tamara D; Donkor, Peter; Obiri-Yeboah, Solomon; Plange-Rhule, Gyikua; Oti, Alexander A; Owais, Arwa; Olaitan, Peter B; Aregbesola, Babatunde S; Oginni, Fadekemi O; Bello, Seidu A; Audu, Rosemary; Onwuamah, Chika; Agbenorku, Pius; Ogunlewe, Mobolanle O; Abdur-Rahman, Lukman O; Marazita, Mary L; Adeyemo, A A; Murray, Jeffrey C; Butali, Azeez

    2018-05-01

    Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

  16. Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine

    Science.gov (United States)

    Huang, Wei; Placzek, Andon N; Viana Di Prisco, Gonzalo; Khatiwada, Sanjeev; Sidrauski, Carmela; Krnjević, Krešimir; Walter, Peter; Dani, John A; Costa-Mattioli, Mauro

    2016-01-01

    Adolescents are especially prone to drug addiction, but the underlying biological basis of their increased vulnerability remains unknown. We reveal that translational control by phosphorylation of the translation initiation factor eIF2α (p-eIF2α) accounts for adolescent hypersensitivity to cocaine. In adolescent (but not adult) mice, a low dose of cocaine reduced p-eIF2α in the ventral tegmental area (VTA), potentiated synaptic inputs to VTA dopaminergic neurons, and induced drug-reinforced behavior. Like adolescents, adult mice with reduced p-eIF2α-mediated translational control were more susceptible to cocaine-induced synaptic potentiation and behavior. Conversely, like adults, adolescent mice with increased p-eIF2α became more resistant to cocaine's effects. Accordingly, metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD)—whose disruption is postulated to increase vulnerability to drug addiction—was impaired in both adolescent mice and adult mice with reduced p-eIF2α mediated translation. Thus, during addiction, cocaine hijacks translational control by p-eIF2α, initiating synaptic potentiation and addiction-related behaviors. These insights may hold promise for new treatments for addiction. DOI: http://dx.doi.org/10.7554/eLife.12052.001 PMID:26928234

  17. Dating brittle tectonic movements with cleft monazite

    DEFF Research Database (Denmark)

    Berger, Alfons; Gnos, E.; Janots, E.

    2013-01-01

    stress axis, which is characteristic for strike slip deformation. The inferred stress situation is consistent with observed kinematics and the opening of such clefts. Therefore, the investigated monazite-bearing cleft formed at the end of D2 and/or D3, and dextral movements along NNW dipping planes...

  18. Ankyloglossia with cleft lip: A rare case report

    Science.gov (United States)

    Jangid, Kritika; Alexander, Aurelian Jovita; Jayakumar, Nadathur Doraiswamy; Varghese, Sheeja; Ramani, Pratibha

    2015-01-01

    Ankyloglossia or tongue-tie is a congenital anomaly affecting the tongue, which is characterized by thick, short lingual frenulum. This condition causes many difficulties such as limited tongue protrusion, breastfeeding difficulties, speech impairment and lack of self-confidence. It is very rarely associated with any other congenital craniofacial disorders such as cleft lip, X-linked cleft palate, Van der Woude syndrome, Smith-Lemli-Opitz syndrome, Orofacial digital syndrome, Beckwith Weidman syndrome or Simpson-Golabi-Behmel syndrome. This article presents a rare case of ankyloglossia associated with cleft lip treated with diode laser in a 12-year-old Indian boy who had undergone surgical correction of associated cleft lip soon after birth. Correction of ankyloglossia at a young age would lead to enhanced phonetics, improved oral hygiene, and overall personality development. PMID:26941523

  19. Ankyloglossia with cleft lip: A rare case report

    Directory of Open Access Journals (Sweden)

    Kritika Jangid

    2015-01-01

    Full Text Available Ankyloglossia or tongue-tie is a congenital anomaly affecting the tongue, which is characterized by thick, short lingual frenulum. This condition causes many difficulties such as limited tongue protrusion, breastfeeding difficulties, speech impairment and lack of self-confidence. It is very rarely associated with any other congenital craniofacial disorders such as cleft lip, X-linked cleft palate, Van der Woude syndrome, Smith-Lemli-Opitz syndrome, Orofacial digital syndrome, Beckwith Weidman syndrome or Simpson-Golabi-Behmel syndrome. This article presents a rare case of ankyloglossia associated with cleft lip treated with diode laser in a 12-year-old Indian boy who had undergone surgical correction of associated cleft lip soon after birth. Correction of ankyloglossia at a young age would lead to enhanced phonetics, improved oral hygiene, and overall personality development.

  20. Branchial cleft anomalies and their mimics: computed tomographic evaluation

    International Nuclear Information System (INIS)

    Harnsberger, H.R.; Mancuso, A.A.; Muraki, A.S.; Byrd, S.E.; Dillon, W.P.; Johnson, L.P.; Hanafee, W.N.

    1984-01-01

    A review was made of the clinical records and radiographic examinations of 38 patients with neck lesions clinically suspected of being branchial cleft anomalies. The impact of computed tomography in this sometimes confusing clinical picture was assessed and CT criteria for diagnosing branchial cleft anomalies (BCAs) and differentiating them from their mimics were identified. Seventeen branchial cleft anomalies and 21 BCA mimics were evaluated. A definitive CT diagnosis of second branchial cleft cysts based on characteristic morphology, location, and displacement of surrounding structures was possible in 80% of cases. CT was found to be the best radiographic examination in making a definitive diagnosis of BCA if a neck mass was present

  1. Banach Synaptic Algebras

    Science.gov (United States)

    Foulis, David J.; Pulmannov, Sylvia

    2018-04-01

    Using a representation theorem of Erik Alfsen, Frederic Schultz, and Erling Størmer for special JB-algebras, we prove that a synaptic algebra is norm complete (i.e., Banach) if and only if it is isomorphic to the self-adjoint part of a Rickart C∗-algebra. Also, we give conditions on a Banach synaptic algebra that are equivalent to the condition that it is isomorphic to the self-adjoint part of an AW∗-algebra. Moreover, we study some relationships between synaptic algebras and so-called generalized Hermitian algebras.

  2. The value of multislice spiral CT in the pre-operative diagnosis of cleft palate

    International Nuclear Information System (INIS)

    Tang Guangxi; Sun Lianfen; Zhang Xiaolin; Yu Chengxin; Lu Ji; Wang Xiaopeng; Li Liya; Yang Cheng; Wang Jun; Tian Yiqing

    2004-01-01

    Objective: To evaluate the practical value of multislice spiral CT (MSCT) in the preoperative diagnosis of cleft palate. Methods: Twenty patients with cleft palate were examined by using thin-slice (1.25 mm/4i) axial MSCT scanning and CT virtual endoscope (CTVE) imaging before and after operations. The cleft of each lesion was measured in the primary axial images. Results: Of the 20 cases, soft-and-hard cleft palate (grade II) was detected in 10 cases, with the clefts of soft palate between 1.5 cm and 2.2 cm, and the clefts of soft-and-hard palate between 1.2 cm and 2.0 cm. The right utter cleft palates were found in 3 cases with the clefts of soft palate between 2.0 cm and 2.5 cm, the clefts of soft-and-hard palate between 2.0 cm and 2.4 cm, and the clefts of hard palate between 1.8 cm and 2.2 cm. The left utter cleft palates (grade III) were found in 5 cases with the clefts of soft palate between 1.2 cm and 1.8 cm, the clefts of soft-and-hard palate between 0.9 cm and 2.0 cm, and the clefts of hard palate between 0.9 cm and 1.8 cm. The bilateral utter cleft palates (grade III) were detected in 2 cases with the clefts of soft palate between 2.1 cm and 2.3 cm, the clefts of soft-and-hard palate between 1.8 cm and 2.0 cm, and the clefts of hard palate between 1.9 cm and 2.3 cm. Conclusion: MSCT could excellently display the shape of all lesions before operation, especially the splitting degree of hard cleft palates in the axial images. Accurate measurements could be done for the cleft of different lesions in MSCT images. CTVE could clearly and directly show the shape of the lesion's interior surface. The pre-operative and post-operative images of each case could be perfectly compared by the combination of MSCT and CTVE

  3. The effects of oral clefts on hospital use throughout the lifespan

    Directory of Open Access Journals (Sweden)

    Wehby George L

    2012-03-01

    Full Text Available Abstract Background Oral clefts are one of the most common birth defects worldwide. They require multiple healthcare interventions and add significant burden on the health and quality of life of affected individuals. However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan. Methods We estimate two-part regression models for hospital admission and length of stay for several age groups up to 68 years of age. The study employs unique secondary population-based data from several administrative inpatient, civil registration, demographic and labor market databases for 7,670 individuals born with oral clefts between 1936 and 2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random sample of the total birth population from 1936 to 2002. Results Oral clefts significantly increase hospital use for most ages below 60 years by up to 233% for children ages 0-10 years and 16% for middle age adults. The more severe cleft forms (cleft lip with palate have significantly larger effects on hospitalizations than less severe forms. Conclusions The results suggest that individuals with oral clefts have higher hospitalization risks than the general population throughout most of the lifespan.

  4. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

    Science.gov (United States)

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-Qian; Wu, Yan; Yang, Hongwei; Tang, Ya-Ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-11-21

    Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Antenatal determinants of oro-facial clefts in Southern Nigeria | Omo ...

    African Journals Online (AJOL)

    Objectives: Cleft lip with or without cleft palate, is the most common serious congenital anomaly that affects the orofacial regions. The management and care of the cleft patient constitutes a substantial proportion of the workload of the Nigerian maxillofacial surgeon and allied specialties. Yet, there are no specific ...

  6. Glutamate dehydrogenase (RocG) in Bacillus licheniformis WX-02: Enzymatic properties and specific functions in glutamic acid synthesis for poly-γ-glutamic acid production.

    Science.gov (United States)

    Tian, Guangming; Wang, Qin; Wei, Xuetuan; Ma, Xin; Chen, Shouwen

    2017-04-01

    Poly-γ-glutamic acid (γ-PGA), a natural biopolymer, is widely used in cosmetics, medicine, food, water treatment, and agriculture owing to its features of moisture sequestration, cation chelation, non-toxicity and biodegradability. Intracellular glutamic acid, the substrate of γ-PGA, is a limiting factor for high yield in γ-PGA production. Bacillus subtilis and Bacillus licheniformis are both important γ-PGA producing strains, and B. subtilis synthesizes glutamic acid in vivo using the unique GOGAT/GS pathway. However, little is known about the glutamate synthesis pathway in B. licheniformis. The aim of this work was to characterize the glutamate dehydrogenase (RocG) in glutamic acid synthesis from B. licheniformis with both in vivo and in vitro experiments. By re-directing the carbon flux distribution, the rocG gene deletion mutant WX-02ΔrocG produced intracellular glutamic acid with a concentration of 90ng/log(CFU), which was only 23.7% that of the wild-type WX-02 (380ng/log(CFU)). Furthermore, the γ-PGA yield of mutant WX-02ΔrocG was 5.37g/L, a decrease of 45.3% compared to the wild type (9.82g/L). In vitro enzymatic assays of RocG showed that RocG has higher affinity for 2-oxoglutarate than glutamate, and the glutamate synthesis rate was far above degradation. This is probably the first study to reveal the glutamic acid synthesis pathway and the specific functions of RocG in B. licheniformis. The results indicate that γ-PGA production can be enhanced through improving intracellular glutamic acid synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Glutamate and GABA in appetite regulation

    Directory of Open Access Journals (Sweden)

    Teresa Cardoso Delgado

    2013-08-01

    Full Text Available Appetite is regulated by a coordinated interplay between gut, adipose tissue and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms.Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using 13C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-13C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-13C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the

  8. Branchial cleft cyst encircling the hypoglossal nerve

    Science.gov (United States)

    Long, Kristin L.; Spears, Carol; Kenady, Daniel E.

    2013-01-01

    Branchial cleft anomalies are a common cause of lateral neck masses and may present with infection, cyst enlargement or fistulas. They may affect any of the nearby neck structures, causing compressive symptoms or vessel thrombosis. We present a case of a branchial cleft cyst in a 10-year-old boy who had been present for 1year. At the time of operation, the cyst was found to completely envelop the hypoglossal nerve. While reports of hypoglossal nerve palsies due to external compression from cysts are known, we believe this to be the first report of direct nerve involvement by a branchial cleft cyst. PMID:24963902

  9. Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

    Science.gov (United States)

    Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

    2016-08-01

    Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes.

  10. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  11. We can predict postpalatoplasty velopharyngeal insufficiency in cleft palate patients.

    Science.gov (United States)

    Leclerc, Jacques E; Godbout, Audrey; Arteau-Gauthier, Isabelle; Lacour, Sophie; Abel, Kati; McConnell, Elisa-Maude

    2014-02-01

    To find an anatomical measurement of the cleft palate (or a calculated parameter) that predicts the occurrence of velopharyngeal insufficiency (VPI) after palatal cleft repair. Retrospective cohort study. Charts were reviewed from cleft palate patients who underwent palatoplasty by the Von Langenbeck technique for isolated cleft palate or Bardach two-flap palatoplasty for cleft lip-palate. Seven anatomical cleft parameters were prospectively measured during the palatoplasty procedure. Three blinded speech-language pathologists retrospectively scored the clinically assessed VPI at 4 years of age. The recommendation of pharyngoplasty was also used as an indicator of VPI. From 1993 to 2008, 67 patients were enrolled in the study. The best predicting parameter was the ratio a/(30 - b1), in which a is defined as the posterior gap between the soft palate and the posterior pharyngeal wall and b1 is the width of the cleft at the hard palate level. An a/(30 - b1) ratio >0.7 to 0.8 is associated with a higher risk of developing VPI (relative risk = 2.2-5.1, sensitivity = 72%-81%, P cleft at the hard palate level and the posterior gap between the soft palate and the posterior pharyngeal wall were found to be the most significant parameters in predicting VPI. The best correlation was obtained with the ratio a/(30 - b1). 4. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Glutamate and Neurodegenerative Disease

    Science.gov (United States)

    Schaeffer, Eric; Duplantier, Allen

    As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

  13. [Recurrent neck abscess due to a branchial cleft remnant].

    Science.gov (United States)

    Kruijff, Schelto; Mastboom, Walter J; Vriens, Menno R; Sidhu, Stan B; Delbridge, Leigh W

    2013-01-01

    Abscesses arising from a third or fourth branchial cleft remnant are uncommon clinical entities and are often not recognised in a timely manner. In a 33-year-old female patient with a recurrent abscess in the left side of her neck, the cause turned out to be a fistula in the third branchial cleft remnant. She was treated initially with antibiotics and prednisone without adequate results. When the abscess was finally surgically drained, she became very ill and was admitted to the ICU with sepsis and multiple organ failure. She was discharged from hospital after six weeks. Four months later, a third-branchial cleft remnant was found during pharyngoscopy, immediately after which the cleft remnant fistula was excised and an ipsilateral hemi-thyroidectomy was performed. In young patients with recurring peri-thyroidal abscesses, a branchial cleft remnant should be considered a causative factor; this could avoid high morbidity and a delay in the appropriate treatment.

  14. PREVALENCE OF CLEFT LIP AND PALATE IN GEORGIA.

    Science.gov (United States)

    Chincharadze, S; Vadachkoria, Z; Mchedlishvili, I

    2017-01-01

    Cleft lip and palate take significant place in congenital malformations. We aimed to study epidemiological peculiarities of these pathologies in Georgia for 2006-2015. We compared magnitude of its distribution with the data from 1981-1990. Prevalence of cleft lip and palate in Georgia in 2006-2015 was 0.95±0.04 per 1000 live births, while in 1981-1990- it was 1.05, i.e. in contrast to 1980's frequency of these pathological conditions decreased to some extent. Distribution of cleft lip and palate varies across the country regions. The most intensive spread has been observed in Mtskheta-Mtianeti region, where prevalence composed 2.28/1000. In the rest of the regions frequency of these pathologies is significantly lower. For instance, in Kakheti the rate is equal to 1,87/1000, in Kvemo Kartli - 1.56/1000, in Shida Kartli - 1.55/1000. In the rest of the regions prevalence rate is lower than the country average. It should be noted that in Tbilisi the rate is as low as 0.80/1000. The lowest level has been reported in Guria - 0.56/1000. Currently cleft lip with palate is the most frequently occurring anomaly in Georgia accounting for 39.8% of all congenital malformations. Cleft lip alone ranks the second - 36.1%, followed by cleft palate (24.1%). These pathologies are more frequent in boys than in girls. 60.3% of the cases are reported in males, in contrast to girls - 39.7% (pcleft palate is the most common among girls, but in our case, it had higher prevalence among boys, 53.6% vs. 46,4%. Thus cleft lip and palate distribution in Georgia is characterized by epidemiological peculiarities, which should be considered in implementation of preventive measures.

  15. The development of speech production in children with cleft palate

    DEFF Research Database (Denmark)

    Willadsen, Elisabeth; Chapman, Kathy

    2012-01-01

    The purpose of this chapter is to provide an overview of speech development of children with cleft palate +/- cleft lip. The chapter will begin with a discussion of the impact of clefting on speech. Next, we will provide a brief description of those factors impacting speech development...... for this population of children. Finally, research examining various aspects of speech development of infants and young children with cleft palate (birth to age five) will be reviewed. This final section will be organized by typical stages of speech sound development (e.g., prespeech, the early word stage...

  16. [Inconformity between soft tissue defect and bony defect in incomplete cleft palate].

    Science.gov (United States)

    Zhou, Xia; Ma, Lian

    2014-12-01

    To evaluate the inconformity between soft tissue defect and bony defect by observing the cleft extent of palate with complete secondary palate bony cleft in incomplete cleft palate patient. The patients with incomplete cleft palate treated in Hospital of Stomatology Peking University from July 2012 to June 2013 were reviewed, of which 75 cases with complete secondary palate bony cleft were selected in this study. The CT scan and intraoral photograph were taken before operation. The patients were classified as four types according to the extent of soft tissue defect. Type 1: soft tissue defect reached incisive foremen region, Type 2 was hard and soft cleft palate, Type 3 soft cleft palate and Type 4 submucous cleft palate. Type 1 was defined as conformity group (CG). The other three types were defined as inconformity group (ICG) and divided into three subgroups (ICG-I), (ICG-II) and (ICG-III). Fifty-seven patients were in ICG group, and the rate of inconformity was 76% (57/75). The percentage of ICG-I, ICG-II and ICG-III was 47% (27/57), 23% (13/57) and 30% (17/57), respevtively. There are different types of soft tissue deformity with complete secondary palate bony cleft. The inconformity between soft tissue and hard tissue defect exits in 3/4 of isolated cleft palate patients.

  17. Presurgical cleft lip and palate orthopedics: an overview

    Science.gov (United States)

    Alzain, Ibtesam; Batwa, Waeil; Cash, Alex; Murshid, Zuhair A

    2017-01-01

    Patients with cleft lip and/or palate go through a lifelong journey of multidisciplinary care, starting from before birth and extending until adulthood. Presurgical orthopedic (PSO) treatment is one of the earliest stages of this care plan. In this paper we provide a review of the PSO treatment. This review should help general and specialist dentists to better understand the cleft patient care path and to be able to answer patient queries more efficiently. The objectives of this paper were to review the basic principles of PSO treatment, the various types of techniques used in this therapy, and the protocol followed, and to critically evaluate the advantages and disadvantages of some of these techniques. In conclusion, we believe that PSO treatment, specifically nasoalveolar molding, does help to approximate the segments of the cleft maxilla and does reduce the intersegment space in readiness for the surgical closure of cleft sites. However, what we remain unable to prove equivocally at this point is whether the reduction in the dimensions of the cleft presurgically and the manipulation of the nasal complex benefit our patients in the long term. PMID:28615974

  18. Prevalence of dental anomalies in patients with cleft lip and palate.

    Science.gov (United States)

    Eslami, Neda; Majidi, Mohammad Reza; Aliakbarian, Majid; Hasanzadeh, Nadia

    2013-09-01

    The aim of the present study was to investigate the prevalence of dental anomalies in a group of patients with cleft lip and palate (CL/P) in the northeast of Iran. Ninety-one patients referring to the Cleft Lip and Palate Clinic of Mashhad Dental School were enrolled and classified into right CL/P, left CL/P, and bilateral CL/P groups. Photographs, dental casts, and panoramic and periapical radiographs were retrieved, and dental anomalies were recorded. χ test was used to analyze the frequency of dental anomalies according to type of cleft and sex. Missing maxillary lateral incisors was the most frequent dental anomaly, which was slightly higher in the bilateral group (61.1%). There were significantly more cases of missing lateral incisors outside the cleft area in right CL/P (P = 0.015). Peg lateral incisors were observed in 33.3% of bilateral CL/P compared with 28% of right and 23.3% of left unilateral cases. The sample presented rotations of central incisors in the cleft area in 33.3% of bilateral clefts. In unilateral clefts, it occurred more frequently in the right side (48%). Sexual dimorphism appeared only for maxillary central incisor rotation in the cleft area, which showed significantly greater frequency in females (P = 0.025). Transposition of maxillary canine and first premolars was found in 5.5% of bilateral, 8% of right, and 3.3% of left unilateral clefts. The prevalence of dental anomalies in the studied sample seems to be higher than that reported in the normal population. More anomalies were observed at the cleft side. The frequency of most anomalies was not significantly different between the 2 sexes.

  19. The impact of cleft lip and palate repair on maxillofacial growth.

    Science.gov (United States)

    Shi, Bing; Losee, Joseph E

    2015-03-23

    Surgical correction is central to current team-approached cleft treatment. Cleft surgeons are always concerned about the impact of their surgical maneuver on the growth of the maxilla. Hypoplastic maxilla, concaved mid-face and deformed dental arch have constantly been reported after cleft treatments. It is very hard to completely circumvent these postoperative complications by current surgical protocols. In this paper, we discussed the factors that inhibit the maxillofacial growth on cleft patients. These factors included pre-surgical intervention, the timing of cleft palate and alveolae repair, surgical design and treatment protocol. Also, we made a review about the influence on the maxillary growth in un-operated cleft patients. On the basis of previous researches, we can conclude that most of scholars express identity of views in these aspects: early palatoplasty lead to maxilla growth inhibition in all dimensions; secondary alveolar bone graft had no influence on maxilla sagittal growth; cleft lip repair inhibited maxilla sagittal length in patients with cleft lip and palate; Veau's pushback palatoplasty and Langenbeck's palatoplasty with relaxing incisions were most detrimental to growth; Furlow palatoplasty showed little detrimental effect on maxilla growth; timing of hard palate closure, instead of the sequence of hard or soft palate repair, determined the postoperative growth. Still, scholars hold controversial viewpoints in some issues, for example, un-operated clefts have normal growth potential or not, pre-surgical intervention and pharyngoplasty inhibited maxillofacial growth or not.

  20. The impact of cleft lip and palate repair on maxillofacial growth

    Science.gov (United States)

    Shi, Bing; Losee, Joseph E

    2015-01-01

    Surgical correction is central to current team-approached cleft treatment. Cleft surgeons are always concerned about the impact of their surgical maneuver on the growth of the maxilla. Hypoplastic maxilla, concaved mid-face and deformed dental arch have constantly been reported after cleft treatments. It is very hard to completely circumvent these postoperative complications by current surgical protocols. In this paper, we discussed the factors that inhibit the maxillofacial growth on cleft patients. These factors included pre-surgical intervention, the timing of cleft palate and alveolae repair, surgical design and treatment protocol. Also, we made a review about the influence on the maxillary growth in un-operated cleft patients. On the basis of previous researches, we can conclude that most of scholars express identity of views in these aspects: early palatoplasty lead to maxilla growth inhibition in all dimensions; secondary alveolar bone graft had no influence on maxilla sagittal growth; cleft lip repair inhibited maxilla sagittal length in patients with cleft lip and palate; Veau's pushback palatoplasty and Langenbeck's palatoplasty with relaxing incisions were most detrimental to growth; Furlow palatoplasty showed little detrimental effect on maxilla growth; timing of hard palate closure, instead of the sequence of hard or soft palate repair, determined the postoperative growth. Still, scholars hold controversial viewpoints in some issues, for example, un-operated clefts have normal growth potential or not, pre-surgical intervention and pharyngoplasty inhibited maxillofacial growth or not. PMID:25394591

  1. Reproductive patterns among Danish women with oral clefts

    DEFF Research Database (Denmark)

    Yttri, Janne Elin; Christensen, Kaare; Knudsen, Lisbeth

    2011-01-01

    Abstract Objective: The aim of the study was to compare the reproduction pattern among Danish women born with isolated oral clefts with the Danish background population. Design and setting: A nationwide population based historic cohort-study based on three registers: The Danish Facial Cleft...... Register, The Danish Civil Registration System and the Fertility of Women and Couples Dataset. Participants: Through linkages of the registers, number of children and the exact age at childbirth of all Danish women born with an oral cleft during 1950 through 1988 (N=1,931) were obtained. These data were...

  2. Strategy for Nasal Reconstruction in Atypical Facial Clefts

    Directory of Open Access Journals (Sweden)

    Fouad M. Ghareeb, FRCS, MD

    2017-11-01

    Full Text Available Summary:. It is difficult to put forward a strategy for the treatment of nasal clefts due to the rarity and diversity of anatomical aberrations of these cases contrary to the common nasal affection in cleft lip and palate patients, which differ in severity rather than differing in the morbid anatomy. This simple strategy for correction of these nasal clefts will hopefully help surgeons to achieve better results. In the mean time I intended to describe the morbid anatomy of these cases by choosing examples of each morbid anatomy.

  3. Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes

    Directory of Open Access Journals (Sweden)

    Brendan S Whitelaw

    2013-09-01

    Full Text Available We recently found evidence for anatomic and physical linkages between the astroglial Na+-dependent glutamate transporters (GLT-1/EAAT2 and GLAST/EAAT1 and mitochondria. In these same studies, we found that the glutamate dehydrogenase (GDH inhibitor, epigallocatechin-monogallate (EGCG, inhibits both glutamate oxidation and Na+-dependent glutamate uptake in astrocytes. In the present study, we extend this finding by exploring the effects of EGCG on Na+-dependent L-[3H]-glutamate (Glu uptake in crude membranes (P2 prepared from rat brain cortex. In this preparation, uptake is almost exclusively mediated by GLT-1. EGCG inhibited L-[3H]-Glu uptake in cortical membranes with an IC50 value of 230 µM. We also studied the effects of two additional inhibitors of GDH, hexachlorophene (HCP and bithionol (BTH. Both of these compounds also caused concentration-dependent inhibition of glutamate uptake in cortical membranes. Pre-incubating with HCP for up to 15 min had no greater effect than that observed with no pre-incubation, showing that the effects occur rapidly. HCP decreased the Vmax for glutamate uptake without changing the Km, consistent with a non-competitive mechanism of action. EGCG, HCP, and BTH also inhibited Na+-dependent transport of D-[3H]-aspartate (Asp, a non-metabolizable substrate, and [3H]-γ-aminobutyric acid (GABA. In contrast to the forebrain, glutamate uptake in crude cerebellar membranes (P2 is likely mediated by GLAST (EAAT1. Therefore, the effects of these compounds were examined in cerebellar membranes. In this region, none of these compounds had any effect on uptake of either L-[3H]-Glu or D-[3H]-Asp, but they all inhibited [3H]-GABA uptake. Together these studies suggest that GDH is preferentially required for glutamate uptake in forebrain as compared to cerebellum, and GDH may be required for GABA uptake as well. They also provide further evidence for a functional linkage between glutamate transport and mitochondria.

  4. Nitric oxide facilitates active avoidance learning via enhancement of glutamate levels in the hippocampal dentate gyrus.

    Science.gov (United States)

    Wang, Shi; Pan, De-Xi; Wang, Dan; Wan, Peng; Qiu, De-Lai; Jin, Qing-Hua

    2014-09-01

    The hippocampus is a key structure for learning and memory in mammals, and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. Despite a number of studies indicating that nitric oxide (NO) is involved in the formation and maintenance of LTP as a retrograde messenger, few studies have used neurotransmitter release as a visual indicator in awake animals to explore the role of NO in learning-dependent long-term enhancement of synaptic efficiency. Therefore, in the present study, the effects of l-NMMA (a NO synthase inhibitor) and SNP (a NO donor) on extracellular glutamate (Glu) concentrations and amplitudes of field excitatory postsynaptic potential (fEPSP) were measured in the hippocampal dentate gyrus (DG) region during the acquisition and extinction of active-avoidance behavior in freely-moving conscious rats. In the control group, the extracellular concentration of Glu in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to baseline levels following extinction training. In the experimental group, the change in Glu concentration was significantly reduced by local microinjection of l-NMMA, as was the acquisition of the active-avoidance behavior. In contrast, the change in Glu concentration was significantly enhanced by SNP, and the acquisition of the active-avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in extracellular Glu were accompanied by corresponding changes in fEPSP amplitude and active-avoidance behavior. Our results suggest that NO in the hippocampal DG facilitates active avoidance learning via enhancements of glutamate levels and synaptic efficiency in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Further evidence of a relationship between the retinoic acid receptor alpha locus and nonsyndromic cleft lip with or without cleft palate (CL [+-] P)

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, D.; Field, L. (Univ. of Calgary (Canada)); Ray, A. (Univ. of Toronto (Canada)); Marazita, M. (Medical College of Virginia, Richmond, VA (United States))

    1993-11-01

    Chenevix-Trench et al. (1992) reported a significant difference between nonsyndromic cleft lip with or without cleft palate (CL [+-] P) cases and unrelated controls in the frequency of alleles at the retinoic acid receptor alpha (RARA) PstI RFLP located at 17q21.1. They also observed borderline significant (P = .055) differences between allele frequencies in subjects with cleft lip and palate (CL + P) compared with those with cleft lip only (CL). Retinoic acid (RA) is a known teratogen capable of producing cleft palate in rodents (Abbott and Birnbaum 1990). Chenevix-Tench et al. (1992) hypothesized that variation in susceptibility to the effects of RA in humans may result from alterations at the RARA locus. We have investigated association and linkage between CL [+-] P and a microsatellite marker (D17S579) located at 17q21 (Hall et al. 1992), selected for its proximity to RARA, in 14 extended multiplex families from rural West Bengal, India.

  6. EDITORIAL: Synaptic electronics Synaptic electronics

    Science.gov (United States)

    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    Conventional computers excel in logic and accurate scientific calculations but make hard work of open ended problems that human brains handle easily. Even von Neumann—the mathematician and polymath who first developed the programming architecture that forms the basis of today's computers—was already looking to the brain for future developments before his death in 1957 [1]. Neuromorphic computing uses approaches that better mimic the working of the human brain. Recent developments in nanotechnology are now providing structures with very accommodating properties for neuromorphic approaches. This special issue, with guest editors James K Gimzewski and Dominique Vuillaume, is devoted to research at the serendipitous interface between the two disciplines. 'Synaptic electronics', looks at artificial devices with connections that demonstrate behaviour similar to synapses in the nervous system allowing a new and more powerful approach to computing. Synapses and connecting neurons respond differently to incident signals depending on the history of signals previously experienced, ultimately leading to short term and long term memory behaviour. The basic characteristics of a synapse can be replicated with around ten simple transistors. However with the human brain having around 1011 neurons and 1015 synapses, artificial neurons and synapses from basic transistors are unlikely to accommodate the scalability required. The discovery of nanoscale elements that function as 'memristors' has provided a key tool for the implementation of synaptic connections [2]. Leon Chua first developed the concept of the 'The memristor—the missing circuit element' in 1971 [3]. In this special issue he presents a tutorial describing how memristor research has fed into our understanding of synaptic behaviour and how they can be applied in information processing [4]. He also describes, 'The new principle of local activity, which uncovers a minuscule life-enabling "Goldilocks zone", dubbed the

  7. Oblique lip-alveolar banding in patients with cleft lip and palate.

    Science.gov (United States)

    Naidoo, S; Bütow, K-W

    2015-04-01

    We report an oblique lip-alveolar band, a rare banding of soft tissue that involves the lip and alveolus, which we have found in five patients with cleft lip and palate (0.2%), compared with an incidence of the Simonartz lip-lip band of 5.7%). To our knowledge this has not been reported previously. In two patients the bands affected the cleft lip and alveolus bilaterally, with or without the palatal cleft, and in three the bands were unilateral cleft lip and alveolus with or without the palatal cleft. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Description of Mexican Cleft Surgeons' Experience With Foreign Surgical Volunteer Missions in Mexico.

    Science.gov (United States)

    Schoenbrunner, Anna R; Kelley, Kristen D; Buckstaff, Taylor; McIntyre, Joyce K; Sigler, Alicia; Gosman, Amanda A

    2018-05-01

    Mexican cleft surgeons provide multidisciplinary comprehensive cleft lip and palate care to children in Mexico. Many Mexican cleft surgeons have extensive experience with foreign, visiting surgeons. The purpose of this study was to characterize Mexican cleft surgeons' domestic and volunteer practice and to learn more about Mexican cleft surgeons' experience with visiting surgeons. A cross-sectional validated e-mail survey tool was sent to Mexican cleft surgeons through 2 Mexican plastic surgery societies and the Asociación Mexicana de Labio y Paladar Hendido y Anomalías Craneofaciales, the national cleft palate society that includes plastic and maxillofacial surgeons who specialize in cleft surgery. We utilized validated survey methodology, including neutral fact-based questions and repeated e-mails to survey nonresponders to maximize validity of statistical data; response rate was 30.6% (n = 81). Mexican cleft surgeons performed, on average, 37.7 primary palate repairs per year with an overall complication rate of 2.5%; 34.6% (n = 28) of respondents had direct experience with patients operated on by visiting surgeons; 53.6% of these respondents performed corrective surgery because of complications from visiting surgeons. Respondents rated 48% of the functional outcomes of visiting surgeons as "acceptable," whereas 43% rated aesthetic outcomes of visiting surgeons as "poor"; 73.3% of respondents were never paid for the corrective surgeries they performed. Thirty-three percent of Mexican cleft surgeons believe that there is a role for educational collaboration with visiting surgeons. Mexican cleft surgeons have a high volume of primary cleft palate repairs in their domestic practice with good outcomes. Visiting surgeons may play an important role in Mexican cleft care through educational collaborations that complement the strengths of Mexican cleft surgeons.

  9. Cleft lip and cleft palate relationship with familial marriage: a study in 136 cases

    Directory of Open Access Journals (Sweden)

    Azimi C

    2010-02-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Clefts of the lip and palate are one of the most common congenital birth anomalies. Genetic factors play a great role in the etiology of them and the high percentage of the consanguineous marriage of the parents of the affected persons is one of the reasons. These defects not only make abnormal changes on appearance of the neonate, but also make a lot of stress and psychological problems for the patients and their families. Study on the prevalence of clefts, their risk factors and also genetic counseling for affected persons and their families can be a guideline for general population and probably reduce these anomalies over the generations."n"nMethods: Patients referred to the Department of Genetics, Imam Khomeini Hospital, Tehran, Iran were studied. A total of 7374 pedigrees of all the patients admitted to the Department, were studied during 2002-2005 and 99 pedigrees with the patients with cleft lip± palate or isolated cleft palate were separated. The total number of cases among these 99 pedigrees was 136. The effects of consanguineous marriage, positive family history and sex were investigated among cases."n"nResults: 70.8% of patients with syndromic clefts and 58.7% of patients with nonsyndromic CL

  10. Neuroembryology and functional anatomy of craniofacial clefts

    Directory of Open Access Journals (Sweden)

    Ewings Ember

    2009-10-01

    Full Text Available The master plan of all vertebrate embryos is based on neuroanatomy. The embryo can be anatomically divided into discrete units called neuromeres so that each carries unique genetic traits. Embryonic neural crest cells arising from each neuromere induce development of nerves and concomitant arteries and support the development of specific craniofacial tissues or developmental fields. Fields are assembled upon each other in a programmed spatiotemporal order. Abnormalities in one field can affect the shape and position of developing adjacent fields. Craniofacial clefts represent states of excess or deficiency within and between specific developmental fields. The neuromeric organization of the embryo is the common denominator for understanding normal anatomy and pathology of the head and neck. Tessier′s observational cleft classification system can be redefined using neuroanatomic embryology. Reassessment of Tessier′s empiric observations demonstrates a more rational rearrangement of cleft zones, particularly near the midline. Neuromeric theory is also a means to understand and define other common craniofacial problems. Cleft palate, encephaloceles, craniosynostosis and cranial base defects may be analyzed in the same way.

  11. Bilateral cleft lip nasal deformity

    Directory of Open Access Journals (Sweden)

    Singh Arun

    2009-01-01

    Full Text Available Bilateral cleft lip nose deformity is a multi-factorial and complex deformity which tends to aggravate with growth of the child, if not attended surgically. The goals of primary bilateral cleft lip nose surgery are, closure of the nasal floor and sill, lengthening of the columella, repositioning of the alar base, achieving nasal tip projection, repositioning of the lower lateral cartilages, and reorienting the nares from horizontal to oblique position. The multiplicity of procedures in the literature for correction of this deformity alludes to the fact that no single procedure is entirely effective. The timing for surgical intervention and its extent varies considerably. Early surgery on cartilage may adversely affect growth and development; at the same time, allowing the cartilage to grow in an abnormal position and contributing to aggravation of deformity. Some surgeons advocate correction of deformity at an early age. However, others like the cartilages to grow and mature before going in for surgery. With peer pressure also becoming an important consideration during the teens, the current trend is towards early intervention. There is no unanimity in the extent of nasal dissection to be done at the time of primary lip repair. While many perform limited nasal dissection for the fear of growth retardation, others opt for full cartilage correction at the time of primary surgery itself. The value of naso-alveolar moulding (NAM too is not universally accepted and has now more opponents than proponents. Also most centres in the developing world have neither the personnel nor the facilities for the same. The secondary cleft nasal deformity is variable and is affected by the extent of the original abnormality, any prior surgeries performed and alteration due to nasal growth. This article reviews the currently popular methods for correction of nasal deformity associated with bilateral cleft lip, it′s management both at the time of cleft lip repair

  12. Health Status Among Adults Born With an Oral Cleft in Norway.

    Science.gov (United States)

    Berg, Erik; Haaland, Øystein A; Feragen, Kristin B; Filip, Charles; Vindenes, Hallvard A; Moster, Dag; Lie, Rolv T; Sivertsen, Åse

    2016-11-01

    Parents regularly express concern about long-term health outcomes for children who are born with an oral cleft. To assess whether oral clefts affect the health and ability to work of young adults. A population-based cohort study was conducted on all individuals born in Norway between calendar years 1967 and 1992 (n = 1 490 401). All patients treated for clefts in Norway during the study period were invited to participate (n = 2860). This study used population-based, long-term follow-up data from national registries to focus on the future health outcomes of individuals with cleft and no additional chronic medical conditions or congenital anomalies. A total of 523 individuals were excluded from the study cohort because they declined participation, could not be reached by mail, or had birth defects other than clefts. The final cohort, consisting of 2337 cases with isolated clefts and 1 413 819 unaffected individuals, was followed up until December 31, 2010, using compulsory national registries and clinical data. Data analysis was conducted from February 13, 2014, to April 18, 2016. Oral clefts. Death, intellectual disability, schizophrenia, mood affective disorders, anxiety disorders, autism spectrum disorders, attention deficit/hyperactivity disorder, severe learning disability, cerebral palsy, epilepsy, muscle or skeletal disorders, trauma, and episodes of reduced health. Of 2860 individuals born with an oral cleft, 2337 were included in the analysis; of these, 1401 were male (59.9%). Mean (SD) age in 2010 was 30.6 (7.7) years. Compared with unaffected individuals, no increased risks were found regarding morbidity or mortality among persons with isolated cleft lip only. Among individuals with isolated cleft lip and cleft palate, increased risks of intellectual disability (relative risk [RR], 2.2; 95% CI, 1.2-4.1) and cerebral palsy (RR, 2.6; 95% CI, 1.1-6.2) were found. Individuals with isolated cleft palate (ie, without cleft lip) had increased mortality

  13. Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms.

    LENUS (Irish Health Repository)

    Corvin, Aiden P

    2012-06-27

    Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.

  14. Evaluation of Teeth Development in Unilateral Cleft Lip and Palate ...

    African Journals Online (AJOL)

    2018-02-23

    Feb 23, 2018 ... in patients with cleft lip and palate using medical software ... to be used in routine dental treatment and in particular the need to do more study. ... cleft palate/lip surgery were examined. ... segment from the “evaluate” tab of the program. Teeth .... cases of cleft palate or lip. ..... of maxillary canines: A CT study.

  15. Incidence of Congenital Heart Diseases Anomalies in Newborns with Oral Clefts, Zahedan, Iran

    Directory of Open Access Journals (Sweden)

    Noor Mohammad Noori

    2016-09-01

    Full Text Available Background Oral cleft is the most common orofacial congenital anomaly among live births. This anomaly at birth is one of the main causes of children disability and mortality.  Congenital heart disease (CHD is one of the most common anomalies in oral clefts.  This study aimed to assess the incidence of congenital heart diseases anomalies in newborns with oral clefts. Materials and Methods This study performed on 48,692 live born to estimate incidence of oral clefts from 1 st December 2013 to 31 th November 2015 from three general hospitals in Zahedan, The capital city of the Sistan & Baluchestan  province, Iran. All oral cleft patients were under echocardiography to diagnosis the incidence of CHD as associated anomaly. The collected data were processed using SPSS-16. Results The results of the analysis showed that the incidence of cleft lip was higher in boys than girls, while the cleft palate was higher in girls. Lip/palate cleft was higher for boys.  Oral clefts patients accounted of 102 (0.2% with incidence rate of 2.095 per 1000 lives. Of 102 patients 19 (18.62%, 39(35.24% and 44(43.14% were oral lip, oral palate and both respectively. The incidence of CHD in patients with oral clefts was 26.5%, while the incidences for cleft lip, cleft palate and both were 15.79%, 20.51%, and 36.36% respectively. Conclusion From the study concluded that the rate of CHD among children with oral clefts was high compared with the healthy children.  Strongly is suggested the echocardiography for these patients to have early diagnostic of CHD to manage any life-threatening.

  16. The structure of a mixed GluR2 ligand-binding core dimer in complex with (S)-glutamate and the antagonist (S)-NS1209

    DEFF Research Database (Denmark)

    Kasper, Christina; Pickering, Darryl S; Mirza, Osman

    2006-01-01

    domains has been observed. (S)-NS1209 adopts a novel binding mode, including hydrogen bonding to Tyr450 and Gly451 of D1. Parts of (S)-NS1209 occupy new areas of the GluR2 ligand-binding cleft, and bind near residues that are not conserved among receptor subtypes. The affinities of (RS)-NS1209 at the Glu....... The thermodynamics of binding of the antagonists (S)-NS1209, DNQX and (S)-ATPO to the GluR2 ligand-binding core have been determined by displacement isothermal titration calorimetry. The displacement of (S)-glutamate by all antagonists was shown to be driven by enthalpy....

  17. Synaptic transmission modulates while non-synaptic processes govern the transition from pre-ictal to seizure activity in vitro

    OpenAIRE

    Jefferys, John; Fox, John; Jiruska, Premysl; Kronberg, Greg; Miranda, Dolores; Ruiz-Nuño, Ana; Bikson, Marom

    2018-01-01

    It is well established that non-synaptic mechanisms can generate electrographic seizures after blockade of synaptic function. We investigated the interaction of intact synaptic activity with non-synaptic mechanisms in the isolated CA1 region of rat hippocampal slices using the 'elevated-K+' model of epilepsy. Elevated K+ ictal bursts share waveform features with other models of electrographic seizures, including non-synaptic models where chemical synaptic transmission is suppressed, such as t...

  18. Association Between Cleft Lip and/or Cleft Palate and Family History of Cancer: A Case-Control Study.

    Science.gov (United States)

    Bui, Anthony H; Ayub, Ayisha; Ahmed, Mairaj K; Taioli, Emanuela; Taub, Peter J

    2018-04-01

    Cleft lip and/or cleft palate (CL ± P) are among the most common congenital anomalies. Nevertheless, their etiologies remain poorly understood. Several studies have demonstrated increased rates of cancer among patients with CL ± P and their relatives, as well as increased risk of CL ± P among family members of cancer survivors. In addition, a number of possible genetic associations between cancer and CL ± P have been identified. However, these studies are limited by confounding factors that may be prevalent in these patients, such as tobacco exposure and perinatal complications.The purpose of this study was to quantitatively evaluate the association between family history of cancer and development of CL ± P in the child. A case-control study was conducted at the Cleft Hospital and the Bashir Hospital in Gujrat, Pakistan from December 2015 to December 2016. All new cases of CL ± P at the Cleft Hospital were included. Sociodemographically similar patients without congenital malformations at the Bashir Hospital served as controls. Risk factors associated with CL ± P were identified through bivariate analyses. Multiple logistic regressions were performed to calculate adjusted odds ratios of developing CL ± P. There were 137 patients with CL ± P and 147 controls in the study. The following factors were statistically significantly associated with development of cleft: history of cancer in the family (P consanguineous marriage (parents are first or second cousins) (P = 0.03), lower socioeconomic status (P relationship between CL ± P and cancer that has been adjusted for confounders traditionally associated with patients with CL ± P, thereby supporting the evidence of shared environmental and/or genetic etiologies.

  19. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo

    DEFF Research Database (Denmark)

    Jessen, Sanne Barsballe; Brazhe, Alexey; Lind, Barbara Lykke

    2015-01-01

    Neural activity regulates local increases in cerebral blood flow (ΔCBF) and the cortical metabolic rate of oxygen (ΔCMRO2) that constitutes the basis of BOLD functional neuroimaging signals. Glutamate signaling plays a key role in brain vascular and metabolic control; however, the modulatory effect...... of GABA is incompletely understood. Here we performed in vivo studies in mice to investigate how THIP (which tonically activates extrasynaptic GABAARs) and Zolpidem (a positive allosteric modulator of synaptic GABAARs) impact stimulation-induced ΔCBF, ΔCMRO2, local field potentials (LFPs), and fluorescent...... cytosolic Ca2+ transients in neurons and astrocytes. Low concentrations of THIP increased ΔCBF and ΔCMRO2 at low stimulation frequencies. These responses were coupled to increased synaptic activity as indicated by LFP responses, and to Ca2+ activities in neurons and astrocytes. Intermediate and high...

  20. Receptosecretory nature of type III cells in the taste bud.

    Science.gov (United States)

    Yoshie, Sumio

    2009-01-01

    Type III cells in taste buds form chemical synapses with intragemmal afferent nerve fibers and are characterized by the presence of membrane-bound vesicles in the cytoplasm. Although the vesicles differ in shape and size among species, they are primarily categorized into small clear (40 nm in diameter) and large dense-cored (90-200 nm) types. As such vesicles tend to be closely juxtaposed to the synaptic membrane of the cells, it is reasonable to consider that the vesicles include transmitter(s) towards the gustatory nerve. In the guinea-pig taste bud, stimulation with various taste substances (sucrose, sodium chloride, quinine hydrochloride, or monosodium L-glutamate) causes ultrastructural alterations of the type III cells. At the synapse, the presynaptic plasma membrane often displays invaginations of 90 nm in a mean diameter towards the cytoplasm, which indicates the dense-cored vesicles opening into the synaptic cleft by means of exocytosis. The vesicles are also exocytosed at the non-synaptic region into the intercellular space. These findings strongly suggest that the transmitters presumably contained in the vesicles are released to conduct the excitement of the type III cells to the nerves and also to exert their paracrine effects upon the surroundings, such as the Ebner's salivary gland, acting as local hormones.

  1. Speech and language development in toddlers with and without cleft palate

    NARCIS (Netherlands)

    Priester, G. H.; Goorhuis-Brouwer, S. M.

    Objective: The effect of early palate closure on speech and language development in children with cleft palate. Design: Comparative study. Setting: University Medical Center Groningen, Cleft Palate Team (The Netherlands). Materials and methods: Forty-three toddlers with cleft palate and thirty-two

  2. [Cleft lip, alveolar and palate sequelae. Proposal of new alveolar score by the Alveolar Cleft Score (ACS) classification].

    Science.gov (United States)

    Molé, C; Simon, E

    2015-06-01

    The management of cleft lip, alveolar and palate sequelae remains problematic today. To optimize it, we tried to establish a new clinical index for diagnostic and prognostic purposes. Seven tissue indicators, that we consider to be important in the management of alveolar sequelae, are listed by assigning them individual scores. The final score, obtained by adding together the individual scores, can take a low, high or maximum value. We propose a new classification (ACS: Alveolar Cleft Score) that guides the therapeutic team to a prognosis approach, in terms of the recommended surgical and prosthetic reconstruction, the type of medical care required, and the preventive and supportive therapy to establish. Current studies are often only based on a standard radiological evaluation of the alveolar bone height at the cleft site. However, the gingival, the osseous and the cellular areas bordering the alveolar cleft sequelae induce many clinical parameters, which should be reflected in the morphological diagnosis, to better direct the surgical indications and the future prosthetic requirements, and to best maintain successful long term aesthetic and functional results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Clefting in pumpkin balloons

    Science.gov (United States)

    Baginski, F.; Schur, W.

    NASA's effort to develop a large payload, high altitude, long duration balloon, the Ultra Long Duration Balloon, focuses on a pumpkin shape super-pressure design. It has been observed that a pumpkin balloon may be unable to pressurize into the desired cyclically symmetric equilibrium configuration, settling into a distorted, undesired stable state instead. Hoop stress considerations in the pumpkin design leads to choosing the lowest possible bulge radius, while robust deployment is favored by a large bulge radius. Some qualitative understanding of design aspects on undesired equilibria in pumpkin balloons has been obtained via small-scale balloon testing. Poorly deploying balloons have clefts, but most gores away from the cleft deploy uniformly. In this paper, we present models for pumpkin balloons with clefts. Long term success of the pumpkin balloon for NASA requires a thorough understanding of the phenomenon of multiple stable equilibria and means for quantitative assessment of measures that prevent their occurrence. This paper attempts to determine numerical thresholds of design parameters that distinguish between properly deploying designs and improperly deploying designs by analytically investigating designs in the vicinity of criticality. Design elements which may trigger the onset undesired equilibria and remedial measures that ensure deployment are discussed.

  4. Contemporary Approaches in the Repair of Alveolar Clefts

    Directory of Open Access Journals (Sweden)

    Ufuk Tatli

    2014-08-01

    Full Text Available Cleft lip and palate is one of the most common craniofacial anomalies. The repair of the alveolar clefts is an important part of the treatment for patients with cleft lip and palate. The treatment concepts of alveolar bone grafting are still controversial. The corresponding controversial issues are; timing of alveolar bone grafting, graft materials, and timing of the orthodontic expansion. In the present article, aforementioned controversial issues and contemporary treatment modalities of the maxillary alveolar clefts were reviewed in the light of current literature. In conclusion, the most suitable time for alveolar bone grafting is mixed dentition period. Grafting procedure may be performed in the early or late phases of this period depending on some clinical features. Adjunct orthodontic expansion procedures should be performed before and/or after grafting depending on the patient's current features. [Archives Medical Review Journal 2014; 23(4.000: 563-574

  5. Maxillary sinus volumes of patients with unilateral cleft lip and palate.

    Science.gov (United States)

    Erdur, Omer; Ucar, Faruk Izzet; Sekerci, Ahmet Ercan; Celikoglu, Mevlut; Buyuk, Suleyman Kutalmıs

    2015-10-01

    Studies about maxillary sinuses of cleft lip-palate patients have increased since sinusitis is commonly observed in these patients. It is evident that maxillary sinus will be morphologically affected in these patients. And anatomic differences may be a cause or at least a contributor of sinusitis. The aim of this study was to compare maxillary sinus volumes of the non-syndromic patients with unilateral cleft lip-palate and control group by using Cone-Beam computed tomography. Tomography scans of 44 unilateral cleft lip-palate patients (18 right and 26 left) with age and gender matched 45 control patients were evaluated for the study. The images used in the study were part of the diagnostic records collected due to dental treatment needs. All tomographs were obtained in supine position by using Cone-Beam computed tomography (NewTom 5G, QR, Verona, Italy). The patient-specific Hounsfield values were set to include the largest amount of voxels in the sinuses volume calculation individually. All data were measured in mm(3). There was no statistically difference between the gender and age distributions of the groups. No statistically significant difference was found on the cleft and non-cleft side, the right and left side of the unilateral cleft lip-palate patients and the control group (P>0.05). For the inter group comparison, mean maxillary sinus volumes volume of unilateral cleft lip-palate patients (9894.55±4171.44mm(3)) was statistically smaller than the control group (11,977.90±4484.93mm(3)) (Pcleft lip-palate patients when compared with the healthy control group. No difference was found on the cleft, non-cleft side and the right-left side of the unilateral cleft lip-palate patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  7. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.H.; van Wamelen, D.J.; Qi, X.R.; Gao, S.F.; Lucassen, P.J.; Swaab, D.F.

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the

  8. Qualitative and quantitative estimation of comprehensive synaptic connectivity in short- and long-term cultured rat hippocampal neurons with new analytical methods inspired by Scatchard and Hill plots

    Energy Technology Data Exchange (ETDEWEB)

    Tanamoto, Ryo; Shindo, Yutaka; Niwano, Mariko [Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University (Japan); Matsumoto, Yoshinori [Department of Applied Physics and Physico-Informatics, Faculty of Science and Technology, Keio University (Japan); Miki, Norihisa [Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522 (Japan); Hotta, Kohji [Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University (Japan); Oka, Kotaro, E-mail: oka@bio.keio.ac.jp [Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University (Japan)

    2016-03-18

    To investigate comprehensive synaptic connectivity, we examined Ca{sup 2+} responses with quantitative electric current stimulation by indium-tin-oxide (ITO) glass electrode with transparent and high electro-conductivity. The number of neurons with Ca{sup 2+} responses was low during the application of stepwise increase of electric current in short-term cultured neurons (less than 17 days in-vitro (DIV)). The neurons cultured over 17 DIV showed two-type responses: S-shaped (sigmoid) and monotonous saturated responses, and Scatchard plots well illustrated the difference of these two responses. Furthermore, sigmoid like neural network responses over 17 DIV were altered to the monotonous saturated ones by the application of the mixture of AP5 and CNQX, specific blockers of NMDA and AMPA receptors, respectively. This alternation was also characterized by the change of Hill coefficients. These findings indicate that the neural network with sigmoid-like responses has strong synergetic or cooperative synaptic connectivity via excitatory glutamate synapses. - Highlights: • We succeed to evaluate the maturation of neural network by Scathard and Hill Plots. • Long-term cultured neurons showed two-type responses: sigmoid and monotonous. • The sigmoid-like increase indicates the cooperatevity of neural networks. • Excitatory glutamate synapses cause the cooperatevity of neural networks.

  9. Cleft lip with or without cleft palate: Associations with transforming growth factor alpha and retinoic acid receptor loci

    Energy Technology Data Exchange (ETDEWEB)

    Chenevix-Trench, G.; Jones, K. (Queensland Inst. of Medical Research (Australia) Univ. of Queensland (Australia)); Green, A.C.; Duffy, D.L.; Martin, N.G. (Queensland Inst. of Medical Research (Australia))

    1992-12-01

    The first association study of cleft lip with or without cleft palate (CL/P), with candidate genes, found an association with the transforming growth-factor alpha (TGFA) locus. This finding has since been replicated, in whole or in part, in three independent studies. Here the authors extend their original analysis of the TGFA TaqI RFLP to two other TGFA RFLPs and seven other RFLPs at five candidate genes in 117 nonsyndromic cases of CL/P and 113 controls. The other candidate genes were the retinoic acid receptor (RARA), the bcl-2 oncogene, and the homeobox genes 2F, 2G, and EN2. Significant associations with the TGFA TaqI and BamHI RFLPs were confirmed, although associations of clefting with previously reported haplotypes did not reach significance. Of particular interest, in view of the known teratogenic role of retinoic acid, was a significant association with the RARA PstI RFLP (P = .016; not corrected for multiple testing). The effect on risk of the A2 allele appears to be additive, and although the A2A2 homozygote only has an odds ratio of about 2 and recurrence risk to first-degree relatives ([lambda][sub 1]) of 1.06, because it is so common it may account for as much as a third of the attributable risk of clefting. There is no evidence of interaction between the TGFA and RARA polymorphisms on risk, and jointly they appear to account for almost half the attributable risk of clefting. 43 refs., 1 fig., 4 tabs.

  10. Communicative abilities in toddlers and in early school age children with cleft palate

    NARCIS (Netherlands)

    Ruiter, Jolien S.; Korsten-Meijer, Astrid G. W.; Goorhuis-Brouwer, Siena M.

    Objectives: Evaluation of improvement in communicative abilities in children with nonsyndromic cleft palate. Methods: Longitudinal retrospective case history Study. Out of 117 children with cleft lip and/or cleft palate born in 1998, 1999 and 2000 and enrolled in the cleft palate team of the

  11. Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes

    DEFF Research Database (Denmark)

    Carlson, Jenna C; Standley, Jennifer; Petrin, Aline

    2017-01-01

    Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes-cleft lip alone (CL) and CL plus cleft palate (CLP)-are typically grouped into a single phenotype for genetic analysis (i.e., CL with or without cleft palate, CL/P)...

  12. Cell-based multi-parametric model of cleft progression during submandibular salivary gland branching morphogenesis.

    Directory of Open Access Journals (Sweden)

    Shayoni Ray

    Full Text Available Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft

  13. RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Kim, Jong Min; Kang, Se Woong; Son, Dae Yong; Bae, Kunho

    2017-11-01

    To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance. Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group). Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P age-related macular degeneration (P age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.

  14. Branchial Cleft Anomalies

    Science.gov (United States)

    McPhail, Neil; Mustard, Robert A.

    1966-01-01

    The embryology, anatomy and pathology of branchial cleft anomalies are discussed and 87 cases reviewed. The most frequent anomaly was branchial cleft cyst, of which there were 77 cases. Treatment in all cases consisted of complete excision. There were five cases of external branchial sinus and five cases of complete branchial fistula. Sinograms were helpful in demonstrating these lesions. Excision presented little difficulty. No proved case of branchiogenic carcinoma has been found in the Toronto General Hospital. Five cases are described in which the original diagnosis was branchiogenic carcinoma—in four of these a primary tumour has already been found. The authors believe that the diagnosis of branchiogenic carcinoma should never be accepted until repeated examinations over a period of at least five years have failed to reveal a primary tumour. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:5901161

  15. The trochlear cleft: the ''black line'' of the trochlear trough

    International Nuclear Information System (INIS)

    Wissman, Robert D.; Nepute, Joshua; Fischer, Nathaniel von; Radhakrishnan, Rupa; Hendry, Daniel; Ingalls, Jerrell; Kenter, Keith

    2012-01-01

    The ''cartilage black line sign'' is a recently described T2 dark cartilage lesion that we have identified appearing as a cleft in the trochlear trough. The purpose of our study was to define the MR imaging characteristics of a trochlear cleft, determine its incidence, and correlate the MR findings with arthroscopy. A total of 1,300 consecutive MR examinations of the knee were retrospectively reviewed by consensus of two fellowship-trained musculoskeletal radiologists. The MR imaging characteristics and location of a trochlear cleft were determined. Imaging results were compared to arthroscopy when available. Patient age and gender were compared to 25 randomly selected control patients without trochlear clefts. A total of 25 (1.9%) individuals (11 females and 14 males; age range 19-45 years; mean age 28 years) were diagnosed with a trochlear cleft. The control group consisted of 11 females and 14 males; age range 19-83 years; mean age 46 years. Mean cleft length was 7 mm (range 6-12 mm); cleft location was consistently in the lower trochlear trough. No full-thickness cartilage defects were identified in the eight individuals in whom arthroscopic correlation was available. A grade 2 cartilage lesion was identified in a single individual; another progressed from grade 0 to a full-thickness trochlear lesion over an 8-month interval. Eight individuals were athletes. No significant difference in gender was noted between the two groups, however, the study group was significantly younger p < 0.0001. A trochlear cleft is a rare finding in young active individuals. It most likely indicates an incomplete cartilage fissure which may rarely progress to a full-thickness defect. (orig.)

  16. A case report of brachial cleft cyst in the neck

    International Nuclear Information System (INIS)

    Lee, Young Mi; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

    1993-01-01

    Branchial cleft cyst is the most common lateral neck cyst ; the vast majority are of the second branchial cleft origin. This presumably reflects the greater depth and longer persistence of the second cleft, compared with the first, third, and fourth clefts. We experienced a 49-year-old male whose chief complaint was a abnormal mass of the cleft parotid gland area and neck. As a result of careful analysis of clinical, radiological, and histopathological findings. We diagnosed it as a second branchial cleft cyst in the neck and obtained results as follows: 1. In clinical examination, there was a 10 X 15 cm sized, fluctuant painful mass in the left neck and parotid area. 2. In radiographic examination, a low echogenic mass with internal cystic change in the inferior parotid gland area was noted sonographically. Computed tomograph showed a 3 X 4 cm sized, well-defined cystic mass with heterogenous solid component in the anterior border of sternocleidomastoid muscle. MRI revealed 5 X 6 cm sized, well-marginated multiseparated mass in the same area. 3. In histopathological examination, lining of cyst was stratified squamous epithelium with typical lymph node pattern and inflammatory cell infiltration.

  17. A case report of brachial cleft cyst in the neck

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Mi; Choi, Soon Chul; Park, Tae Won; You, Dong Soo [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1993-08-15

    Branchial cleft cyst is the most common lateral neck cyst ; the vast majority are of the second branchial cleft origin. This presumably reflects the greater depth and longer persistence of the second cleft, compared with the first, third, and fourth clefts. We experienced a 49-year-old male whose chief complaint was a abnormal mass of the cleft parotid gland area and neck. As a result of careful analysis of clinical, radiological, and histopathological findings. We diagnosed it as a second branchial cleft cyst in the neck and obtained results as follows: 1. In clinical examination, there was a 10 X 15 cm sized, fluctuant painful mass in the left neck and parotid area. 2. In radiographic examination, a low echogenic mass with internal cystic change in the inferior parotid gland area was noted sonographically. Computed tomograph showed a 3 X 4 cm sized, well-defined cystic mass with heterogenous solid component in the anterior border of sternocleidomastoid muscle. MRI revealed 5 X 6 cm sized, well-marginated multiseparated mass in the same area. 3. In histopathological examination, lining of cyst was stratified squamous epithelium with typical lymph node pattern and inflammatory cell infiltration.

  18. Nonsyndromic cleft lip with or without cleft palate: New BCL3 information

    Energy Technology Data Exchange (ETDEWEB)

    Amos, C.; Hecht, J.T. [Univ. of Texas Medical School, Houston, TX (United States); Gasser, D. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    1996-09-01

    We did not previously provide LOD scores for linkage assuming heterogeneity, as suggested by Ott for the linkage analysis of cleft lip with or without cleft palate (CL/P) and BCL3, ApoC2, and D19S178 in the paper by Stein et al. The results from analysis using the HOMOG program, allowing for heterogeneity under the reduced penetrance model, gave a maximum LOD score of 1.85 for ApoC2, 0.41 for BCL3, 0.03 for D19S178, and 1.72 for multipoint analysis in the interval. For the affecteds-only model, the values are 1.96 for ApoC2, 0.41 for BCL3, 0.01 for D19S178, and 1.44 for the multipoint analysis. 8 refs.

  19. Parental age in relation to severity of clefting

    DEFF Research Database (Denmark)

    Hermann, Nuno Vibe; Darvann, Tron Andre; Kreiborg, Sven

    2016-01-01

    Lip and/or Palate (IC). Wilcoxon Rank-Sum test (5% significance level) was applied in order to test for group differences. Standard logistic regression was used in order to estimate the risk of developing CC relative to IC. Results. In the group with CC mean paternal age was 29.5+/-4.5 (1SD) years...... parental ages in the group with IC did not differ from normative population values during the same time period. Logistic regression showed for paternal age OR=1.1[1.04,1.16](Wald confidence limits); for maternal age 1.08[1.01,1.15]. Conclusions. The hypothesis was rejected. Parental age was significantly...... of cleft individuals, as well as to compare parental age in the cleft population with normative values of parental age. It was hypothesized that there was no difference in parental age between the cleft groups with incomplete and complete clefts, respectively. Methods/Descriptions. The consecutive non...

  20. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase.

    Science.gov (United States)

    Liang, Bo; Zhang, Shu; Lang, Qiaolin; Song, Jianxia; Han, Lihui; Liu, Aihua

    2015-07-16

    A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP(+)-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP(+) involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current-time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM-1 mM and 2-10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N=3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Sonographic detection of intrathyroidal branchial cleft cyst: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hye-Jeong; Kim, Eun-Kyung; Hong, Soon-Won [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2006-06-15

    We report here on an extremely rare case of an intrathyroidal branchial cleft cyst. Intrathyroidal branchial cleft cyst is rare disease entity and it nonspecific findings on sonography, so the diagnosis of the lesion is very difficult. However, during aspiration, if pus-like materials are aspirated from a thyroid cyst, we should consider the possibility of intrathyroidal branchial cleft cyst in the differential diagnosis.

  2. Sonographic detection of intrathyroidal branchial cleft cyst: a case report

    International Nuclear Information System (INIS)

    Lee, Hye-Jeong; Kim, Eun-Kyung; Hong, Soon-Won

    2006-01-01

    We report here on an extremely rare case of an intrathyroidal branchial cleft cyst. Intrathyroidal branchial cleft cyst is rare disease entity and it nonspecific findings on sonography, so the diagnosis of the lesion is very difficult. However, during aspiration, if pus-like materials are aspirated from a thyroid cyst, we should consider the possibility of intrathyroidal branchial cleft cyst in the differential diagnosis

  3. Prevalence of dental anomalies of number in different subphenotypes of isolated cleft palate

    Directory of Open Access Journals (Sweden)

    João Paulo Schwartz

    2014-01-01

    Full Text Available OBJECTIVE: This study aimed at carrying out a radiographic analysis on the prevalence of dental anomalies of number (agenesis and supernumerary teeth in permanent dentition, in different subphenotypes of isolated cleft palate pre-adolescent patients. METHODS: Panoramic radiographs of 300 patients aged between 9 and 12 years, with cleft palate and enrolled in a single treatment center, were retrospectively analyzed. The sample was divided into two groups according to the extension/severity of the cleft palate: complete and incomplete . The chi-square test was used for intergroup comparison regarding the prevalence of the investigated dental anomalies (P < 0.05. RESULTS: Agenesis was found in 34.14% of patients with complete cleft palate and in 30.27% of patients with incomplete cleft palate. Supernumerary teeth were found in 2.43% of patients with complete cleft palate and in 0.91% of patients with incomplete cleft palate. No statistically significant difference was found between groups with regard to the prevalence of agenesis and supernumerary teeth. There was no difference in cleft prevalence between genders within each study group. CONCLUSION: The prevalence of dental anomalies of number in pre-adolescents with cleft palate was higher than that reported for the general population. The severity of cleft palate did not seem to be associated with the prevalence of dental anomalies of number.

  4. [Psychosocial adjustment in children with a cleft lip and/or palate].

    Science.gov (United States)

    Hoek, Ineke H C; Kraaimaat, Floris W; Admiraal, Ronald J C; Kuijpers-Jagtman, Anne Marie; Verhaak, Christianne M

    2009-01-01

    To gain insight into the psychosocial health of children aged 9 to 12 years with a cleft lip and/or palate; to determine the relation between their health and the nature and severity of the cleft as well as other individual characteristics. Descriptive, cross-sectional study. Questionnaires completed by parents, teachers and children were used to obtain information about the psychosocial health, nature and severity of the cleft lip and/or palate, and individual characteristics of 80 children. The interrelationship between these parameters was assessed using chi-square tests, single-factor analysis of variance and correlational analysis. In general, the psychosocial health of children with a cleft lip and/or palate did not differ from that of the norm groups. Parents of children with a cleft lip/and or palate reported more withdrawn or depressive behaviour in their child than parents from the norm groups. Children with a cleft lip and/or palate exhibited less rule-breaking behaviour. Teachers reported relatively more social problems. One-third of the children had learning problems. A better psychosocial health was associated with fewer speech problems but not with a more or less abnormal physical appearance. Self-image showed a negative correlation with psychosocial health problems, while learning problems showed a positive correlation. In general, the psychosocial health of children with a cleft lip and/or palate does not differ from children without this condition. However, children with a cleft lip and/or palate do exhibit more learning problems.

  5. Replication of 13q31.1 Association in Nonsyndromic Cleft Lip with Cleft Palate in Europeans

    Science.gov (United States)

    Cooper, Margaret E.; Butali, Azeez; Standley, Jennifer; Rigdon, Jennifer; Suzuki1, Satoshi; Gongorjav, Ayana; Shonkhuuz, T. Enkhtur; Natsume, Nagato; Shi, Bing; Marazita, Mary L.; Murray, Jeffrey C.

    2015-01-01

    Genome wide association (GWA) studies have successfully identified at least a dozen loci associated with orofacial clefts. However, these signals may be unique to specific populations and require replication to validate and extend findings as a prelude to etiologic SNP discovery. We attempted to replicate the findings of a recent meta-analysis of orofacial cleft GWA studies using four different ancestral populations. We studied 946 pedigrees (3436 persons) of European (US white and Danish) and Asian (Japanese and Mongolian) origin. We genotyped six SNPs which represented the most significant P value associations identified in published studies: rs742071 (1p36), rs7590268 (2p21), rs7632427 (3p11.1), rs12543318 (8q21.3), rs8001641 (13q31.1) and rs7179658 (15q22.2). We directly sequenced three non-coding conserved regions 200kb downstream of SPRY2 in 713 cases, 438 controls, and 485 trios from the US, Mongolia, and the Philippines. We found rs8001641 to be significantly associated with cleft lip with cleft palate (NSCLP) in Europeans (p-value=4 × 10−5, ORtransmission=1.86 with 95% confidence interval: 1.38-2.52). We also found several novel sequence variants in the conserved regions in Asian and European samples, which may help to localize common variants contributing directly to the risk for NSCLP. This study confirms the prior association between rs8001641 and NSCLP in European populations. PMID:25786657

  6. Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.

    Science.gov (United States)

    Aguilar, Jenny I; Dunn, Matthew; Mingote, Susana; Karam, Caline S; Farino, Zachary J; Sonders, Mark S; Choi, Se Joon; Grygoruk, Anna; Zhang, Yuchao; Cela, Carolina; Choi, Ben Jiwon; Flores, Jorge; Freyberg, Robin J; McCabe, Brian D; Mosharov, Eugene V; Krantz, David E; Javitch, Jonathan A; Sulzer, David; Sames, Dalibor; Rayport, Stephen; Freyberg, Zachary

    2017-08-30

    The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Expression of Glutamate and GABA during the Process of Rat Retinal Synaptic Plasticity Induced by Acute High Intraocular Pressure

    International Nuclear Information System (INIS)

    Zhou, Lihong; Huang, Jufang; Wang, Hui; Luo, Jia; Zeng, Leping; Xiong, Kun; Chen, Dan

    2013-01-01

    Acute high intraocular pressure (HIOP) can induce plastic changes of retinal synapses during which the expression of the presynaptic marker synaptophysin (SYN) has a distinct spatiotemporal pattern from the inner plexiform layer to the outer plexiform layer. We identified the types of neurotransmitters in the retina that participated in this process and determined the response of these neurotransmitters to HIOP induction. The model of acute HIOP was established by injecting normal saline into the anterior chamber of the rat eye. We found that the number of glutamate-positive cells increased successively from the inner part to the outer part of the retina (from the ganglion cell layer to the inner nuclear layer to the outer nuclear layer) after HIOP, which was similar to the spatiotemporal pattern of SYN expression (internally to externally) following HIOP. However, the distribution and intensity of GABA immunoreactivity in the retina did not change significantly at different survival time post injury and had no direct correlation with SYN expression. Our results suggested that the excitatory neurotransmitter glutamate might participate in the plastic process of retinal synapses following acute HIOP, but no evidence was found for the role of the inhibitory neurotransmitter GABA

  8. Cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans.

    Directory of Open Access Journals (Sweden)

    Dania eVecchia

    2015-02-01

    Full Text Available Familial hemiplegic migraine type 1 (FHM1 is caused by gain-of-function mutations in CaV2.1 (P/Q-type Ca2+ channels. Knockin (KI mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses. Enhanced cortical glutamate release was shown to cause the facilitation of cortical spreading depression (CSD in R192Q KI mice. It, however, remains unknown how other FHM1 mutations affect cortical synaptic transmission. Here, we studied neurotransmission in cortical neurons in microculture from KI mice carrying the S218L mutation, which causes a severe FHM syndrome in humans and an allele-dosage dependent facilitation of experimental CSD in KI mice, which is larger than that caused by the R192Q mutation. We show gain-of-function of excitatory neurotransmission, due to increased action-potential evoked Ca2+ influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission at multipolar interneuron synapses in S218L KI mice. In contrast with the larger gain-of-function of neuronal CaV2.1 current in homozygous than heterozygous S218L KI mice, the gain-of-function of evoked glutamate release, the paired-pulse ratio and the Ca2+ dependence of the EPSC were all similar in homozygous and heterozygous S218L KI mice, suggesting compensatory changes in the homozygous mice. Furthermore, we reveal a unique feature of S218L KI cortical synapses which is the presence of a fraction of mutant CaV2.1 channels being open at resting potential. Our data suggest that, while the gain-of-function of evoked glutamate release may explain the facilitation of CSD in heterozygous S218L KI mice, the further facilitation of CSD in homozygous S218L KI mice is due to other CaV2.1-dependent mechanisms, that likely include Ca2+ influx at voltages sub-threshold for action

  9. What does magnetic resonance imaging add to the prenatal ultrasound diagnosis of facial clefts?

    Science.gov (United States)

    Mailáth-Pokorny, M; Worda, C; Krampl-Bettelheim, E; Watzinger, F; Brugger, P C; Prayer, D

    2010-10-01

    Ultrasound is the modality of choice for prenatal detection of cleft lip and palate. Because its accuracy in detecting facial clefts, especially isolated clefts of the secondary palate, can be limited, magnetic resonance imaging (MRI) is used as an additional method for assessing the fetus. The aim of this study was to investigate the role of fetal MRI in the prenatal diagnosis of facial clefts. Thirty-four pregnant women with a mean gestational age of 26 (range, 19-34) weeks underwent in utero MRI, after ultrasound examination had identified either a facial cleft (n = 29) or another suspected malformation (micrognathia (n = 1), cardiac defect (n = 1), brain anomaly (n = 2) or diaphragmatic hernia (n = 1)). The facial cleft was classified postnatally and the diagnoses were compared with the previous ultrasound findings. There were 11 (32.4%) cases with cleft of the primary palate alone, 20 (58.8%) clefts of the primary and secondary palate and three (8.8%) isolated clefts of the secondary palate. In all cases the primary and secondary palate were visualized successfully with MRI. Ultrasound imaging could not detect five (14.7%) facial clefts and misclassified 15 (44.1%) facial clefts. The MRI classification correlated with the postnatal/postmortem diagnosis. In our hands MRI allows detailed prenatal evaluation of the primary and secondary palate. By demonstrating involvement of the palate, MRI provides better detection and classification of facial clefts than does ultrasound alone. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

  10. Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, G.M.; Wasserman, C.R.; O`Malley, C.D. [California Birth Defects Monitoring Program, Emeryville, CA (United States)] [and others

    1996-03-01

    Results of studies determine whether women who smoke during early pregnancy are at increased risk of delivering infants with orofacial clefts have been mixed, and recently a gene-environment interaction between maternal smoking, transforming growth factor-alpha (TGFa), and clefting has been reported. Using a large population-based case-control study, we investigated whether parental periconceptional cigarette smoking was associated with an increased risk for having offspring with orofacial clefts. We also investigated the influence of genetic variation of the TGFa locus on the relation between smoking and clefting. Parental smoking information was obtained from telephone interviews with mothers of 731 (84.7% of eligible) orofacial cleft case infants and with mothers of 734 (78.2%) nonmalformed control infants. DNA was obtained from newborn screening blood spots and genotyped for the allelic variants of TGFa. We found that risks associated with maternal smoking were most elevated for isolated cleft lip with or without cleft palate, (odds ratio 2.1 [95% confidence interval 1.3-3.6]) and for isolated cleft palate (odds ratio 2.2 [1.1-4.5]) when mothers smoked {ge} 20 cigarrettes/d. These risks for white infants ranged from 3-fold to 11-fold across phenotypic groups. Paternal smoking was not associated with clefting among the offspring of nonsmoking mothers, and passive smoke exposures were associated with at most slightly increased risks. This study offers evidence that the risk for orofacial clefting in infants may be influenced by maternal smoke exposures alone as well as in combination (gene-environment interaction) with the presence of the uncommon TGFa allele. 56 refs., 5 tabs.

  11. Receptive and expressive language performance in children with and without Cleft Lip and Palate.

    Science.gov (United States)

    Lamônica, Dionísia Aparecida Cusin; Silva-Mori, Mariana Jales Felix da; Ribeiro, Camila da Costa; Maximino, Luciana Paula

    2016-01-01

    To compare the performance in the abilities of receptive and expressive language of children with cleft lip and palate with that of children without cleft lip and palate with typical 12 to 36-month chronological development. The sample consisted of 60 children aged 12 and 36 months: 30 with cleft lip and palate diagnosis and 30 without cleft lip and palate diagnosis with typical development. The groups were paired according to gender, age (in months), and socioeconomic level. The procedures consisted of analysis of medical records, anamnesis with family members, and valuation of the Early Language Milestone Scale (ELMS). The chart analysis showed 63.34% of the children with unilateral cleft lip and palate, 16.66% with bilateral incisive transforamen cleft, and 20% with post-foramen cleft. Children with cleft lip and palate underwent surgeries (lip repair and/or palatoplasty) at the recommended ages and participated in early intervention programs; 40% presented recurrent otitis history, and 50% attended schools. Statistical analysis included the use of the Mann Whitney test with significance level of p cleft lip and palate showed statistically significant low performance in receptive and expressive language compared with children without cleft lip and palate.

  12. PVR/CD155 Ala67Thr Mutation and Cleft Lip/Palate.

    Science.gov (United States)

    Vieira, Alexandre R; Letra, Ariadne; Silva, Renato M; Granjeiro, Jose M; Shimizu, Takehiko; Poletta, Fernando A; Mereb, Juan C; Castilla, Eduardo E; Orioli, Iêda M

    2018-03-01

    The 19q13 locus has been linked to cleft lip and palate by our group and independently by others. Here we fine mapped the region in an attempt to identify an etiological variant that can explain cleft lip and palate occurrence. A total of 2739 individuals born with cleft lip and palate, related to individuals born with cleft lip and palate, and unrelated were studied. We used linkage and association approaches to fine map the interval between D19S714 and D19S433 and genotypes were defined by the use of TaqMan chemistry. We confirmed our previous findings that markers in PVR/CD155 are associated with cleft lip and palate. We studied the mutation Ala67Thr further and calculated its penetrance. We also attempted to detect PVR/CD155 expression in human whole saliva. Our results showed that markers in PVR/CD155 are associated with cleft lip and palate and the penetrance of the Ala67Thr is very low (between 1% and 5%). We could not detect PVR/CD155 expression in adult human whole saliva and PVR/CD155 possibly interacts with maternal infection to predispose children to cleft lip only.

  13. Initial counselling for cleft lip and palate: parents' evaluation, needs and expectations.

    Science.gov (United States)

    Kuttenberger, J; Ohmer, J N; Polska, E

    2010-03-01

    During the first counselling after the birth of a child with cleft lip and palate (CLP) information about the malformation should be delivered and a long-standing relationship between the cleft team and the affected family must be established. The present study was conducted to evaluate the parents' experiences, needs and expectations with this first consultation. A questionnaire was sent to 105 parents at the cleft clinic, which could be answered anonymously. It collected demographic data, data on the parents' pre-existing level of information and the parents' assessment of the counselling at the cleft centre. Seventy percent of the questionnaires were returned. In 16% the clefts were diagnosed prenatally, in 32% there were relatives with clefts. Seventy-one percent of the parents received detailed counselling, 89% of which occurred in the first week. The parents requested that information about surgery (80%), feeding the child (63%) and the aetiology of clefts (44%) should be given. The quality of the consultation was rated very good or good by 87% of families. This study confirms the importance of initial counselling for CLP. The exceptional psychological situation of the family has to be considered and a close collaboration between cleft centre and maternity hospitals is mandatory.

  14. Current Controversies in Diagnosis and Management of Cleft Palate and Velopharyngeal Insufficiency

    Science.gov (United States)

    Ysunza, Pablo Antonio; Repetto, Gabriela M.; Pamplona, Maria Carmen; Calderon, Juan F.; Shaheen, Kenneth; Chaiyasate, Konkgrit; Rontal, Matthew

    2015-01-01

    Background. One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI). Objective. This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate. Materials and Methods. An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy. Results. Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented. Conclusion. This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management. PMID:26273595

  15. Current Controversies in Diagnosis and Management of Cleft Palate and Velopharyngeal Insufficiency

    Directory of Open Access Journals (Sweden)

    Pablo Antonio Ysunza

    2015-01-01

    Full Text Available Background. One of the most controversial topics concerning cleft palate is the diagnosis and treatment of velopharyngeal insufficiency (VPI. Objective. This paper reviews current genetic aspects of cleft palate, imaging diagnosis of VPI, the planning of operations for restoring velopharyngeal function during speech, and strategies for speech pathology treatment of articulation disorders in patients with cleft palate. Materials and Methods. An updated review of the scientific literature concerning genetic aspects of cleft palate was carried out. Current strategies for assessing and treating articulation disorders associated with cleft palate were analyzed. Imaging procedures for assessing velopharyngeal closure during speech were reviewed, including a recent method for performing intraoperative videonasopharyngoscopy. Results. Conclusions from the analysis of genetic aspects of syndromic and nonsyndromic cleft palate and their use in its diagnosis and management are presented. Strategies for classifying and treating articulation disorders in patients with cleft palate are presented. Preliminary results of the use of multiplanar videofluoroscopy as an outpatient procedure and intraoperative endoscopy for the planning of operations which aimed to correct VPI are presented. Conclusion. This paper presents current aspects of the diagnosis and management of patients with cleft palate and VPI including 3 main aspects: genetics and genomics, speech pathology and imaging diagnosis, and surgical management.

  16. An evaluation of factors influencing feeding in babies with a cleft palate with and without a cleft lip.

    Science.gov (United States)

    Martin, Vanessa; Greatrex-White, Sheila

    2014-03-01

    The objective of this article was to determine the impact of different bottles and teats for feeding babies with a cleft palate (with and without a cleft lip) on weight velocity, feeding behaviour, and maternal self-esteem. A mixed methods study incorporating the use of diaries to record feeding patterns of babies and levels of professional support received was used. Growth was assessed by converting weights into standard deviation scores and using the differences to express weight velocity over a six-week period. Visual analogue scales were used to assess mothers' perceptions of their children and themselves. The Edinburgh Postnatal Depression Score (EPDS) was used to identify maternal depression. The study demonstrated that the most significant effect on weight was determined by cleft type. Babies with isolated clefts of the hard and soft palate experienced greater feeding problems and suffered the biggest weight losses. This remained significant independently of the type of bottle/teat used. Poor weight gain was also associated with a mother's low perception of herself and her child, and her tendency towards depression. The study highlights the importance of the early assessment of babies' feeding skills and regular follow-up and support from trained and experienced nurse specialists.

  17. Possible Estrogen Dependency in the Pathogenesis of Branchial Cleft Cysts

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    Jan D. Raguse

    2017-01-01

    Full Text Available Background. Even though branchial cleft cysts are currently accepted as a congenital anomaly, there is often a long delay until clinical presentation; branchial cleft cysts classically appear in the second to fourth decade of life. Our observation of their occurrence in three pregnant women encouraged us to contemplate a possible hormonal influence. Methods. Immunohistological analysis was performed for the evaluation of the estrogen receptor alpha (ERα in paraffin-embedded tissue specimens of 16 patients with a diagnosis of branchial cleft cyst, with three of them being pregnant. Results. Expression of ERα was detected within epithelial cells only in branchial cleft cysts in pregnant females; moreover, higher growth fractions (Ki-67/Mib1 were found. Conclusion. The fact that the estrogen receptor was expressed only in pregnant women, in contrast to 13 investigated cases, may suggest that the high level of estrogen in pregnancy is a possible explanation for the spontaneous growth of branchial cleft cysts.

  18. Possible Estrogen Dependency in the Pathogenesis of Branchial Cleft Cysts.

    Science.gov (United States)

    Raguse, Jan D; Anagnostopoulos, Ioannis; Doll, Christian; Heiland, Max; Jöhrens, Korinna

    2017-01-01

    Even though branchial cleft cysts are currently accepted as a congenital anomaly, there is often a long delay until clinical presentation; branchial cleft cysts classically appear in the second to fourth decade of life. Our observation of their occurrence in three pregnant women encouraged us to contemplate a possible hormonal influence. Immunohistological analysis was performed for the evaluation of the estrogen receptor alpha (ER α ) in paraffin-embedded tissue specimens of 16 patients with a diagnosis of branchial cleft cyst, with three of them being pregnant. Expression of ER α was detected within epithelial cells only in branchial cleft cysts in pregnant females; moreover, higher growth fractions (Ki-67/Mib1) were found. The fact that the estrogen receptor was expressed only in pregnant women, in contrast to 13 investigated cases, may suggest that the high level of estrogen in pregnancy is a possible explanation for the spontaneous growth of branchial cleft cysts.

  19. Safe sleeping positions: practice and policy for babies with cleft palate.

    Science.gov (United States)

    Davies, Karen; Bruce, Iain A; Bannister, Patricia; Callery, Peter

    2017-05-01

    Guidance recommends 'back to sleep' positioning for infants from birth in order to reduce the risk of sudden infant death. Exceptions have been made for babies with severe respiratory difficulties where lateral positioning may be recommended, although uncertainty exists for other conditions affecting the upper airway structures, such as cleft palate. This paper presents research of (i) current advice on sleep positioning provided to parents of infants with cleft palate in the UK; and (ii) decision making by clinical nurse specialists when advising parents of infants with cleft palate. A qualitative descriptive study used data from a national survey with clinical nurse specialists from 12 regional cleft centres in the UK to investigate current practice. Data were collected using semi-structured telephone interviews and analysed using content analysis. Over half the regional centres used lateral sleep positioning based on clinical judgement of the infants' respiratory effort and upper airway obstruction. Assessment relied upon clinical judgement augmented by a range of clinical indicators, such as measures of oxygen saturation, heart rate and respiration. Specialist practitioners face a clinical dilemma between adhering to standard 'back to sleep' guidance and responding to clinical assessment of respiratory effort for infants with cleft palate. In the absence of clear evidence, specialist centres rely on clinical judgement regarding respiratory problems to identify what they believe is the most appropriate sleeping position for infants with cleft palate. Further research is needed to determine the best sleep position for an infant with cleft palate. What is Known • Supine sleep positioning reduces the risk of sudden infant death in new born infants. • There is uncertainty about the benefits or risks of lateral sleep positioning for infants with upper airway restrictions arising from cleft palate. What is New • Variability exists in the information

  20. Activation of extrasynaptic, but not synaptic, NMDA receptors modifies amyloid precursor protein expression pattern and increases amyloid-ß production.

    Science.gov (United States)

    Bordji, Karim; Becerril-Ortega, Javier; Nicole, Olivier; Buisson, Alain

    2010-11-24

    Calcium is a key mediator controlling essential neuronal functions depending on electrical activity. Altered neuronal calcium homeostasis affects metabolism of amyloid precursor protein (APP), leading to increased production of β-amyloid (Aβ), and contributing to the initiation of Alzheimer's disease (AD). A linkage between excessive glutamate receptor activation and neuronal Aβ release was established, and recent reports suggest that synaptic and extrasynaptic NMDA receptor (NMDAR) activation may have distinct consequences in plasticity, gene regulation, and neuronal death. Here, we report for the first time that prolonged activation of extrasynaptic NMDAR, but not synaptic NMDAR, dramatically increased the neuronal production of Aβ. This effect was preceded by a shift from APP695 to Kunitz protease inhibitory domain (KPI) containing APPs (KPI-APPs), isoforms exhibiting an important amyloidogenic potential. Conversely, after synaptic NMDAR activation, we failed to detect any KPI-APP expression and neuronal Aβ production was not modified. Calcium imaging data showed that intracellular calcium concentration after extrasynaptic NMDAR stimulation was lower than after synaptic activation. This suggests distinct signaling pathways for each pool of receptors. We found that modification of neuronal APP expression pattern triggered by extrasynaptic NMDAR activation was regulated at an alternative splicing level involving calcium-/calmodulin-dependent protein kinase IV, but overall APP expression remained identical. Finally, memantine dose-dependently inhibited extrasynaptic NMDAR-induced KPI-APPs expression as well as neuronal Aβ release. Altogether, these data suggest that a chronic activation of extrasynaptic NMDAR promotes amyloidogenic KPI-APP expression leading to neuronal Aβ release, representing a causal risk factor for developing AD.

  1. MRI findings of fetal cleft lip and palate

    International Nuclear Information System (INIS)

    Wang Guangbin; Chen Liguang; Zhu Xiangyu; Wang Cuiyan; Zhang Yinghua; Wang Liajuan; Li Huihua; Qiu Xiuling; Qu Lei; Wei Yulong; Ding Rui; Sun Xueqin

    2010-01-01

    Objective: To investigate the MR findings of fetal cleft lip (CL) and evaluate the advantages and limitations of MRI in the diagnosis. Methods: Twelve pregnant women suspicious of fetal CL/cleft palate (CP) on ultrasonography were enrolled in the study. The findings of ultrasonography, MRI and following-up were compared. Results: MRI and ultrasonography detected 12 fetuses with CL/CP. The following-up results showed 1 case with incomplete cleft lip and the other 11 cases with complete cleft lips and cleft palates. MRI and unltrasonography were consistent with the follow-up in CL detection, showing completed or uncompleted soft tissue interruption of the fetal lips with amniotic fluid filling which is high signal on T 2 WI. On MRI, CP showed discontinuous of the soft tissue which were interrupted by long T 2 signal and communicating with oral cavity ad nasal cavity. MRI missed 1 case and excluded 1 case of CP. Ultrasonography predicted 5 case of CL, excluded 1 CP but missed 6 cases. The accuracy, sensitivity and specificity in detection CL/CP was 91.7% (11/12), 90.9% (10/11), 100% (1/1) for MRI and 50.0% (6/12), 45.5% (5/11), 100% (1/1) for ultrasonography, respectively. Conclusion: MR imaging had advantage over ultrasonography in detecting CP, MRI is an essential when CP is suspicious on ultrasonography. (authors)

  2. Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis

    Science.gov (United States)

    Morales, Juan; Rodríguez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Angel

    2013-01-01

    Geometrical features of chemical synapses are relevant to their function. Two critical components of the synaptic junction are the active zone (AZ) and the postsynaptic density (PSD), as they are related to the probability of synaptic release and the number of postsynaptic receptors, respectively. Morphological studies of these structures are greatly facilitated by the use of recent electron microscopy techniques, such as combined focused ion beam milling and scanning electron microscopy (FIB/SEM), and software tools that permit reconstruction of large numbers of synapses in three dimensions. Since the AZ and the PSD are in close apposition and have a similar surface area, they can be represented by a single surface—the synaptic apposition surface (SAS). We have developed an efficient computational technique to automatically extract this surface from synaptic junctions that have previously been three-dimensionally reconstructed from actual tissue samples imaged by automated FIB/SEM. Given its relationship with the release probability and the number of postsynaptic receptors, the surface area of the SAS is a functionally relevant measure of the size of a synapse that can complement other geometrical features like the volume of the reconstructed synaptic junction, the equivalent ellipsoid size and the Feret's diameter. PMID:23847474

  3. [Suture simulator - Cleft palate surgery].

    Science.gov (United States)

    Devinck, F; Riot, S; Qassemyar, A; Belkhou, A; Wolber, A; Martinot Duquennoy, V; Guerreschi, P

    2017-04-01

    Cleft palate requires surgery in the first years of life, furthermore repairing anatomically the soft and hard palate is complex on a surgical level because of the fine tissues and the local intraoral configuration. It is valuable to train first on simulators before going to the operating room. However, there is no material dedicated to learning how to perform intraoral sutures in cleft palate surgery. We made one, in an artisanal manner, in order to practice before the real surgical gesture. The simulator was designed based on precise anatomical data. A steel pipe, fixed on a rigid base represented the oral cavity. An adapted split spoon represented the palate. All pieces could be removed in order to apply a hydrocellular dressing before training for sutures. Our simulator was tested by 3 senior surgeons in our department in close to real-life conditions in order to evaluate its anatomical accuracy. It is valuable to have a simulator to train on cleft palate sutures within teaching university hospitals that manage this pathology. Our simulator has a very low cost, it is easy to make and is anatomically accurate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Attitudes of pregnant women and mothers of children with orofacial clefts toward prenatal diagnosis of nonsyndromic orofacial clefts in a semiurban set-up in India

    OpenAIRE

    Kadagad, Poornima; Pinto, Pascal; Powar, Rajesh

    2011-01-01

    Objectives: To assess the attitudes of pregnant women and mothers of children with orofacial clefts toward prenatal diagnosis of clefts and elective termination of pregnancy, and to investigate their opinion about who makes reproductive decisions in the family. Design: Two hundred subjects were included in the study prospectively regarding hypothetical prenatal ultrasound diagnosis of clefts. Setting: The study was done in a private tertiary care institution and a teaching hospital. Subjects/...

  5. Augmentation Rhinoplasty in Cleft Lip Nasal Deformity: Preliminary Patients’ Perspective

    Directory of Open Access Journals (Sweden)

    William H. C. Tiong

    2014-01-01

    Full Text Available The correction of cleft lip nasal deformity is challenging and there have been numerous methods described in the literature with little demonstrated technical superiority of one over another. The common clinical issues associated with cleft lip nasal deformity are its lack of symmetry, alar collapse on the affected side, obtuse nasal labial angle, short nasal length, loss of tip definition, and altered columella show among others. We carried out augmentation of cleft lip rhinoplasties with rib graft in 16 patients over the one-year study period. Each of these patients was reviewed and given questionnaire before and after surgery to evaluate their response on the outcome to the approach. Preoperatively, nasal asymmetry is the main complaint (14/16, 87.5% among our series of patients. Postoperatively, 12 (75% patients out of the 16 reported significant improvement in their nasal symmetry with the other four marginal. All patients reported excellent nasal projection postoperatively with good nasal tip definition. Our series of patients reported overall good satisfaction outcome and will recommend this procedure to other patients with cleft lip nasal deformity. In conclusion, augmentation of cleft lip rhinoplasty can be employed to achieve perceivable and satisfactory outcome in patients with cleft lip nasal deformity.

  6. Third branchial cleft anomaly presenting as a retropharyngeal abscess.

    Science.gov (United States)

    Huang, R Y; Damrose, E J; Alavi, S; Maceri, D R; Shapiro, N L

    2000-08-31

    Branchial cleft anomalies are congenital developmental defects that typically present as a soft fluctuant mass or fistulous tract along the anterior border of the sternocleidomastoid muscle. However, branchial anomalies can manifest atypically, presenting diagnostic and therapeutic challenges. Error or delay in diagnosis can lead to complications, recurrences, and even life-threatening emergencies. We describe a case of an infected branchial cleft cyst that progressed to a retropharyngeal abscess in a 5-week-old female patient. The clinical, radiographic, and histologic findings of this rare presentation of branchial cleft cyst are discussed.

  7. Radiographic study on maxillary sinus development and nasal septum deviation in cleft palate patient

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sam Sun; You, Dong Soo [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1992-08-15

    This study was designed to investigate the effects of the maxillary sinus development and nasal septum deviation on diseases of maxillary sinus with cleft palate. The materials was 152 cephalometric Waters' projections consist of 76 cleft patients and 76 normal subjects. The results were as follows: 1. The disease of maxillary sinus was present in 49% of a cleft group and 14% of a control group, and prevalent in cleft side. 2. It showed no statistically significant difference in size of the maxillary sinus in cleft palate patients compared to the control population and in the cleft side to the noncleft side (p<0.05). 3. Nasal septum deviation was more severe in the cleft patient its average value was 3.55mm, compared to the control group, 0.99 mm (p<0.01) and 77% of the deviated nasal septum was deviated to the cleft side.

  8. Radiographic study on maxillary sinus development and nasal septum deviation in cleft palate patient

    International Nuclear Information System (INIS)

    Lee, Sam Sun; You, Dong Soo

    1992-01-01

    This study was designed to investigate the effects of the maxillary sinus development and nasal septum deviation on diseases of maxillary sinus with cleft palate. The materials was 152 cephalometric Waters' projections consist of 76 cleft patients and 76 normal subjects. The results were as follows: 1. The disease of maxillary sinus was present in 49% of a cleft group and 14% of a control group, and prevalent in cleft side. 2. It showed no statistically significant difference in size of the maxillary sinus in cleft palate patients compared to the control population and in the cleft side to the noncleft side (p<0.05). 3. Nasal septum deviation was more severe in the cleft patient its average value was 3.55mm, compared to the control group, 0.99 mm (p<0.01) and 77% of the deviated nasal septum was deviated to the cleft side.

  9. Surgical treatment of cleft lip

    Directory of Open Access Journals (Sweden)

    Mateus Domingues Miachon

    Full Text Available We performed a systematic review of the literature on the surgical treatment of cleft lip, emphasizing the prevalence, complications associated with the treatment and the points of disagreement between authors. We conducted a literature cross-sectional search that analyzed publications in books, articles and on the databases SciELO - Scientific Electronic Library Online, PubMed, of the National Center for Biotechnology Information. We conclude that: 1 the severity of the cleft will indicate the technique presenting more advantages; 2 the different approaches indicate that there is no consensus on the optimal technique; and 3 the surgeon experience contributes to choosing the best option.

  10. Synaptic Remodeling Generates Synchronous Oscillations in the Degenerated Outer Mouse Retina

    Directory of Open Access Journals (Sweden)

    Wadood eHaq

    2014-09-01

    Full Text Available During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs establish contacts with remnant cone photoreceptors (cones as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs, we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from HCs. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells.

  11. Evaluation of 22q11.2 deletion in Cleft Palate patients

    Science.gov (United States)

    Prabodha, L. B. Lahiru; Dias, Dayanath Kumara; Nanayakkara, B. Ganananda; de Silva, Deepthi C.; Chandrasekharan, N. Vishvanath; Ileyperuma, Isurani

    2012-01-01

    Background: Cleft palate is the commonest multifactorial epigenetic disorder with a prevalence of 0.43-2.45 per 1000. The objectives of this study were to evaluate the clinical features and identify the 22q11.2 deletion in patients with cleft palate in Sri Lanka. Materials and Methods: Cleft patients attending a Teaching Hospital in Sri Lanka were recruited for this study. The relevant data were obtained from review of case notes, interviews, and examination of patients according to a standard evaluation sheet. Quantitative multiplex polymerase chain reaction (PCR) was performed to identify the 22q11.2 deletion. A gel documentation system (Bio-Doc) was used to quantify the PCR product following electrophoresis on 0.8% agarose gel. Results and Conclusion: There were 162 cleft palate patients of whom 59% were females. A total of 92 cleft palate subjects (56.2%) had other associated clinical features. Dysmorphic features (25.27%) and developmental delays (25.27%) were the commonest medical problems encountered. The cleft was limited to the soft palate in 125 patients, while in 25 patients it involved both the hard and the soft palate. There were seven subjects with bifid uvula and five subjects with submucous cleft palate. None of the patients had 22q11.2 deletion in this study population. A multicentered large population-based study is needed to confirm the results of this study and to develop guidelines on the appropriate use of 22q11.2 deletion testing, which are valid for cleft palate patients in Sri Lanka. PMID:23483617

  12. Cone-Beam Computed Tomography Analysis of the Nasopharyngeal Airway in Nonsyndromic Cleft Lip and Palate Subjects.

    Science.gov (United States)

    Al-Fahdawi, Mahmood Abd; Farid, Mary Medhat; El-Fotouh, Mona Abou; El-Kassaby, Marwa Abdelwahab

    2017-03-01

      To assess the nasopharyngeal airway volume, cross-sectional area, and depth in previously repaired nonsyndromic unilateral cleft lip and palate versus bilateral cleft lip and palate patients compared with noncleft controls using cone-beam computed tomography with the ultimate goal of finding whether cleft lip and palate patients are more liable to nasopharyngeal airway obstruction.   A retrospective analysis comparing bilateral cleft lip and palate, unilateral cleft lip and palate, and control subjects. Significance at P ≤ .05.   Cleft Care Center and the outpatient clinic that are both affiliated with our faculty.   Cone-beam computed tomography data were selected of 58 individuals aged 9 to 12 years: 14 with bilateral cleft lip and palate and 20 with unilateral cleft lip and palate as well as 24 age- and gender-matched noncleft controls.   Volume, depth, and cross-sectional area of nasopharyngeal airway were measured.   Patients with bilateral cleft lip and palate showed significantly larger nasopharyngeal airway volume than controls and patients with unilateral cleft lip and palate (P cleft lip and palate showed significantly larger cross-sectional area than those with unilateral cleft lip and palate (P .05). Patients with bilateral cleft lip and palate showed significantly larger depth than controls and those with unilateral cleft lip and palate (P cleft lip and palate showed insignificant nasopharyngeal airway volume, cross-sectional area, and depth compared with controls (P > .05).   Unilateral and bilateral cleft lip and palate patients did not show significantly less volume, cross-sectional area, or depth of nasopharyngeal airway than controls. From the results of this study we conclude that unilateral and bilateral cleft lip and palate patients at the studied age and stage of repaired clefts are not more prone to nasopharyngeal airway obstruction than controls.

  13. Comparison of oral hygiene and periodontal status in patients with clefts of palate and patients with unilateral cleft lip, palate and alveolus

    Directory of Open Access Journals (Sweden)

    Mutthineni Ramesh

    2010-01-01

    Full Text Available Aim: This study was conducted to analyze and compare the oral hygiene and periodontal status in patients with clefts of palate (CP and patients with unilateral cleft lip, palate and alveolus (UCLPA. Materials and Methods: The study group consisted of 120 cleft patients. Subjects were divided into two groups of 60 each. Group I - patients with UCLPA and Group II - patients with CP. For comparison, all the four quadrants were defined, Q1-right upper quadrant, Q2-left upper quadrant, Q3-left lower quadrant and Q4-right lower quadrant, in both groups and the following parameters were recorded: Plaque Index (PI, Silness and Loe, Sulcus Bleeding Index (SBI, Muhlemann and Son, Probing Pocket Depth (PPD, Clinical Attachment Level (CAL, Mobility Index (Miller and Radiographic Amount of Bone Loss. Results: The periodontal destruction was seen to be higher in UCLPA patients compared with CP patients. The poor oral hygiene status, as indicated by higher values of PI, and the periodontal status, evaluated by SBI, PPD, CAL, mobility and Radiographic Amount of Bone Loss, were higher in patients with UCLPA than in patients with CP. Conclusion: In this study, patients with cleft lip, palate and alveolus had poor oral hygiene and periodontal status compared with patients with cleft palate.

  14. Second branchial cleft cyst of the oropharynx

    International Nuclear Information System (INIS)

    Paik, Sang Hyun; Kim, Hyun Sook; Moon Seung Il; Choi, Yun Sun; Cho, Jae Min; Cho, Sung Bum; Yoon, Sook Ja; Kim, Dai Hong; Yoon, Yong Kyu

    2001-01-01

    We report a very rare type of second branchial cleft cyst located at the oropharynx, and include a review of the literature. CT scans of the neck revealed a homogeneous non-enhancing low-density mass in the right posterolateral mucosal wall of the oropharynx. Only the peripheral capsule of the mass was enhanced. The cyst was resected perorally and proved to be a type-IV second branchial cleft cyst

  15. Second branchial cleft cyst of the oropharynx

    Energy Technology Data Exchange (ETDEWEB)

    Paik, Sang Hyun; Kim, Hyun Sook; Moon Seung Il; Choi, Yun Sun; Cho, Jae Min; Cho, Sung Bum; Yoon, Sook Ja; Kim, Dai Hong; Yoon, Yong Kyu [Eulji Univ. School of Medicine, Seoul (Korea, Republic of)

    2001-06-01

    We report a very rare type of second branchial cleft cyst located at the oropharynx, and include a review of the literature. CT scans of the neck revealed a homogeneous non-enhancing low-density mass in the right posterolateral mucosal wall of the oropharynx. Only the peripheral capsule of the mass was enhanced. The cyst was resected perorally and proved to be a type-IV second branchial cleft cyst.

  16. Synaptic Plasticity and Nociception

    Institute of Scientific and Technical Information of China (English)

    ChenJianguo

    2004-01-01

    Synaptic plasticity is one of the fields that progresses rapidly and has a lot of success in neuroscience. The two major types of synaptie plasticity: long-term potentiation ( LTP and long-term depression (LTD are thought to be the cellular mochanisms of learning and memory. Recently, accumulating evidence suggests that, besides serving as a cellular model for learning and memory, the synaptic plasticity involves in other physiological or pathophysiological processes, such as the perception of pain and the regulation of cardiovascular system. This minireview will focus on the relationship between synaptic plasticity and nociception.

  17. Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate.

    Science.gov (United States)

    Leslie, Elizabeth J; Carlson, Jenna C; Shaffer, John R; Buxó, Carmen J; Castilla, Eduardo E; Christensen, Kaare; Deleyiannis, Frederic W B; Field, Leigh L; Hecht, Jacqueline T; Moreno, Lina; Orioli, Ieda M; Padilla, Carmencita; Vieira, Alexandre R; Wehby, George L; Feingold, Eleanor; Weinberg, Seth M; Murray, Jeffrey C; Marazita, Mary L

    2017-06-01

    Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common human birth defects with complex etiology. Although genome-wide association studies have successfully identified a number of risk loci, these loci only account for about 20% of the heritability of orofacial clefts. The "missing" heritability may be found in rare variants, copy number variants, or interactions. In this study, we investigated the role of low-frequency variants genotyped in 1995 cases and 1626 controls on the Illumina HumanCore + Exome chip. We performed two statistical tests, Sequence Kernel Association Test (SKAT) and Combined Multivariate and Collapsing (CMC) method using two minor allele frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of NSCL/P. Low-frequency variants in other genes were associated with decreased risk of NSCL/P. These results demonstrate that low-frequency variants contribute to the genetic etiology of NSCL/P. © 2017 Wiley Periodicals, Inc.

  18. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  19. Cleft lip and palate in the arts: a critical reflection.

    Science.gov (United States)

    Saman, Masoud; Gross, Justin; Ovchinsky, Alexander; Wood-Smith, Donald

    2012-03-01

    The aesthetics of facial structure are used by humans to measure one's beauty, character, and overall "goodness." Individuals born with cleft lip and/or palate are often stigmatized and face much psychosocial adversity. Social attitudes and beliefs have a direct impact upon the psychological development of these individuals. Such social norms are in large part shaped by the physical representations of "good" and "attractive" in various art media including films, advertisements, and paintings. Individuals born with a cleft have been portrayed in the artworks of different eras. The light in which they are portrayed stems from the prevalent beliefs of each period and sheds light on the social attitudes of each epoch toward clefts. Here we discuss the social and psychological ramifications of these works. We then review several artworks representing cleft lip and/or palate and propose an active role for the artist in shaping social attitudes regarding facial deformities. Numerous articles and works of arts were examined and inspected for signs of facial deformity, with particular attention to cleft lip and/or palate. Social media have an important role in defining the norms of society. Much of the art of the past has depicted negatively individuals born with cleft lip and/or palate deformity, thus excluding them from the norm. In order to decrease the negative social stigmas of cleft lip and/or palate, it is now the responsibility of society to widen its range of norms to include individuals born with these deformities through "normal" representations in the various media.

  20. Critical analysis of consecutive unilateral cleft lip repairs: determining ideal sample size.

    Science.gov (United States)

    Power, Stephanie M; Matic, Damir B

    2013-03-01

    Objective : Cleft surgeons often show 10 consecutive lip repairs to reduce presentation bias, however the validity remains unknown. The purpose of this study is to determine the number of consecutive cases that represent average outcomes. Secondary objectives are to determine if outcomes correlate with cleft severity and to calculate interrater reliability. Design : Consecutive preoperative and 2-year postoperative photographs of the unilateral cleft lip-nose complex were randomized and evaluated by cleft surgeons. Parametric analysis was performed according to chronologic, consecutive order. The mean standard deviation over all raters enabled calculation of expected 95% confidence intervals around a mean tested for various sample sizes. Setting : Meeting of the American Cleft Palate-Craniofacial Association in 2009. Patients, Participants : Ten senior cleft surgeons evaluated 39 consecutive lip repairs. Main Outcome Measures : Preoperative severity and postoperative outcomes were evaluated using descriptive and quantitative scales. Results : Intraclass correlation coefficients for cleft severity and postoperative evaluations were 0.65 and 0.21, respectively. Outcomes did not correlate with cleft severity (P  =  .28). Calculations for 10 consecutive cases demonstrated wide 95% confidence intervals, spanning two points on both postoperative grading scales. Ninety-five percent confidence intervals narrowed within one qualitative grade (±0.30) and one point (±0.50) on the 10-point scale for 27 consecutive cases. Conclusions : Larger numbers of consecutive cases (n > 27) are increasingly representative of average results, but less practical in presentation format. Ten consecutive cases lack statistical support. Cleft surgeons showed low interrater reliability for postoperative assessments, which may reflect personal bias when evaluating another surgeon's results.