387 research outputs found
Identifying Tinnitus-Related Genes Based on a Side-Effect Network Analysis
Tinnitus, phantom sound perception, is a worldwide highly prevalent disorder for which no clear underlying pathology has been established and for which no approved drug is on the market. Thus, there is an urgent need for new approaches to understand this condition. We used a network pharmacology side-effect analysis to search for genes that are involved in tinnitus generation. We analyzed a network of 1,313 drugâtarget pairs, based on 275 compounds that elicit tinnitus as side effect and their targets reported in databases, and used a quantitative score to identify emergent significant targets that were more common than expected at random. Cyclooxigenase 1 and 2 were significant, which validates our approach, since salicylate is a known tinnitus generator. More importantly, we predict previously unknown tinnitus-related targets. The present results have important implications toward understanding tinnitus pathophysiology and might pave the way toward the design of novel pharmacotherapies.Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; ArgentinaFil: Langguth, B.. University of Regensburg. Interdisciplinary Tinnitus Clinic. Department of Psychiatry and Psychotherapy; AlemaniaFil: Nowak, Wanda. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de FarmacologĂa; ArgentinaFil: Schecklmann, M.. University of Regensburg. Interdisciplinary Tinnitus Clinic. Department of Psychiatry and Psychotherapy; AlemaniaFil: de Ridder, D.. University of Otago. Dunedin School of Medicine. Unit of Neurosurgery. Department of Surgical Sciences; Nueva ZelandaFil: Vanneste, S.. University of Texas at Dallas. School of Behavioral and Brain Sciences. Laboratory for Auditory & Integrative Neuroscience; Estados Unido
Emerging pharmacotherapy of tinnitus
Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en IngenierĂa GenĂ©tica y BiologĂa Molecular "Dr. HĂ©ctor N. Torres"; Argentin
Accessing directly the properties of fundamental scalars in the confinement and Higgs phase
The properties of elementary particles are encoded in their respective
propagators and interaction vertices. For a SU(2) gauge theory coupled to a
doublet of fundamental complex scalars these propagators are determined in both
the Higgs phase and the confinement phase and compared to the Yang-Mills case,
using lattice gauge theory. Since the propagators are gauge-dependent, this is
done in the Landau limit of 't Hooft gauge, permitting to also determine the
ghost propagator. It is found that neither the gauge boson nor the scalar
differ qualitatively in the different cases. In particular, the gauge boson
acquires a screening mass, and the scalar's screening mass is larger than the
renormalized mass. Only the ghost propagator shows a significant change.
Furthermore, indications are found that the consequences of the residual
non-perturbative gauge freedom due to Gribov copies could be different in the
confinement and the Higgs phase.Comment: 11 pages, 6 figures, 1 table; v2: one minor error corrected; v3: one
appendix on systematic uncertainties added and some minor changes, version to
appear in EPJ
Paired Associative Stimulation of the Auditory System: A Proof-Of-Principle Study
Background
Paired associative stimulation (PAS) consisting of repeated application of transcranial magnetic stimulation (TMS) pulses and contingent exteroceptive stimuli has been shown to induce neuroplastic effects in the motor and somatosensory system. The objective was to investigate whether the auditory system can be modulated by PAS.
Methods
Acoustic stimuli (4 kHz) were paired with TMS of the auditory cortex with intervals of either 45 ms (PAS(45 ms)) or 10 ms (PAS(10 ms)). Two-hundred paired stimuli were applied at 0.1 Hz and effects were compared with low frequency repetitive TMS (rTMS) at 0.1 Hz (200 stimuli) and 1 Hz (1000 stimuli) in eleven healthy students. Auditory cortex excitability was measured before and after the interventions by long latency auditory evoked potentials (AEPs) for the tone (4 kHz) used in the pairing, and a control tone (1 kHz) in a within subjects design.
Results
Amplitudes of the N1-P2 complex were reduced for the 4 kHz tone after both PAS(45 ms) and PAS(10 ms), but not after the 0.1 Hz and 1 Hz rTMS protocols with more pronounced effects for PAS(45 ms). Similar, but less pronounced effects were observed for the 1 kHz control tone.
Conclusion
These findings indicate that paired associative stimulation may induce tonotopically specific and also tone unspecific human auditory cortex plasticity
Matching conditions and Higgs mass upper bounds revisited
Matching conditions relate couplings to particle masses. We discuss the
importance of one-loop matching conditions in Higgs and top-quark sector as
well as the choice of the matching scale. We argue for matching scales
and . Using these
results, the two-loop Higgs mass upper bounds are reanalyzed. Previous results
for few TeV are found to be too stringent. For
GeV we find GeV, the first error
indicating the theoretical uncertainty, the second error reflecting the
experimental uncertainty due to GeV.Comment: 20 pages, 6 figures; uses epsf and rotate macro
Biowaiver Monographs for ImmediateâRelease Solid Oral Dosage Forms: Codeine Phosphate
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106898/1/jps23977.pd
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