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1.
Int J Neurosci ; 131(5): 433-444, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32281466

RESUMEN

Background. This proof-of-concept study investigated a method of multisensory perceptual training for tinnitus, and whether a short, low-dose administration of fluoxetine enhanced training effects and changed neural connectivity.Methods. A double-blind, randomized placebo controlled design with 20 participants (17 male, 3 female, mean age = 57.1 years) involved 30 min daily computer-based, multisensory training (matching visual, auditory and tactile stimuli to perception of tinnitus) for 20 days, and random allocation to take 20 mg fluoxetine or placebo daily. Behavioral measures of tinnitus and correlations between pairs of a priori regions of interest (ROIs), obtained using resting-state functional magnetic resonance imaging (rs-fMRI), were performed before and after the training.Results. Significant changes in ratings of tinnitus loudness, annoyance, and problem were observed with training. No statistically significant changes in Tinnitus Functional Index, Tinnitus Handicap Inventory or Depression Anxiety Stress Scales were found with training. Fluoxetine did not alter any of the behavioural outcomes of training compared to placebo. Significant changes in connectivity between ROIs were identified with training; sensory and attention neural network ROI changes correlated with significant tinnitus rating changes. Rs-fMRI results suggested that the direction of functional connectivity changes between auditory and non-auditory networks, with training and fluoxetine, were opposite to the direction of those changes with multisensory training and placebo.Conclusions. Improvements in tinnitus measures were correlated with changes in sensory and attention networks. The results provide preliminary evidence for changes in rs-fMRI accompanying a multisensory training method in persons with tinnitus.


Asunto(s)
Percepción Auditiva , Conectoma , Fluoxetina/farmacología , Rehabilitación Neurológica , Plasticidad Neuronal/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Acúfeno/tratamiento farmacológico , Acúfeno/rehabilitación , Percepción del Tacto , Percepción Visual , Adulto , Anciano , Percepción Auditiva/fisiología , Terapia Combinada , Método Doble Ciego , Femenino , Fluoxetina/administración & dosificación , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Prueba de Estudio Conceptual , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Terapia Asistida por Computador , Percepción del Tacto/fisiología , Percepción Visual/fisiología
2.
Int J Neurosci ; 130(7): 671-682, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31814488

RESUMEN

Background: This study was conducted to investigate the short-term behavioural and neurophysiological effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus perception.Methods: A double-blind randomized controlled cross-over design. Part 1. Behavioural measures of tinnitus following 30 mg MDMA or placebo administration (N = 5 participants) and Part 2. Behavioural measures of tinnitus and correlations between pairs of apriori regions of interest (ROI) using resting-state functional magnetic resonance imaging (rs-fMRI) before and after 70 mg of MDMA or placebo (N = 8 participants).Results: The results to MDMA were similar to placebo. For the 70 mg dose, there was a significant reduction after 4 h in annoyance and ignore ratings. RsMRI showed decreased connectivity compared with placebo administration between the left hippocampal, right hippocampal, left amygdala and right amygdala regions, and between the right posterior parahippocampal cortex and the left amygdala after two hours of 70 mg MDMA administration. Increased connectivity compared to placebo administration was found post MDMA between the right post-central gyrus and right posterior and superior temporal gyrus, and between the thalamus and frontoparietal network.Conclusions: Following 70 mg of MDMA two tinnitus rating scales significantly improved. There was, however, a placebo effect. Compared with placebo the rsMRI following the MDMA showed reductions in connectivity between the amygdala, hippocampus and parahippocampal gyrus. There is sufficient proof of concept to support future investigation of MDMA as a treatment for tinnitus.


Asunto(s)
Encéfalo/efectos de los fármacos , N-Metil-3,4-metilenodioxianfetamina/administración & dosificación , Psicotrópicos/administración & dosificación , Acúfeno/tratamiento farmacológico , Encéfalo/fisiopatología , Mapeo Encefálico , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Acúfeno/fisiopatología
3.
Forensic Sci Int ; 186(1-3): 63-7, 2009 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-19261399

RESUMEN

There have been many reports of benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) being used as recreational drugs which have been widely marketed in the form of 'party pills' since the late 1990's. However, there is no information currently available describing the pharmacokinetics of these drugs in humans. Human plasma concentrations of BZP were measured in blood and urine samples taken from healthy adults (n=7) over 24h following a 200mg oral dose of BZP. Plasma concentrations of BZP were found to peak at 262 ng/mL (C(max)) and 75min (T(max)). Plasma concentrations of the major metabolites of BZP, 4-OH BZP and 3-OH BZP, were found to peak at 7 ng/mL (at 60 min) and 13 ng/mL (at 75 min) respectively. The elimination half-life (t(1/2)) for BZP was found to be 5.5h. Clearance (Cl/F) was found to be 99L/h. The results of this study indicate that BZP may be detectable in plasma for up to 30 h following an oral dose. Additionally, several urinary metabolites can be detected.


Asunto(s)
Piperazinas/farmacocinética , Adulto , Disponibilidad Biológica , Toxicología Forense , Semivida , Humanos , Masculino , Estructura Molecular , Piperazinas/sangre , Piperazinas/orina , Espectrometría de Masa por Ionización de Electrospray
4.
Pharmacol Biochem Behav ; 68(3): 565-74, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11325413

RESUMEN

The glycine site-specific N-methyl-D-aspartate (NMDA) antagonist 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021, 4x30 mg/kg, i.p.) given 30 min before dexfenfluramine (4x15 mg/kg, i.p., every 2 h) was unable to prevent dexfenfluramine-induced depletion of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) content, and 5-HT transporter (5-HTT) density. Another glycine site-specific NMDA antagonist, R(+)-3-aminohydroxypyrrolidin-2-one [(R)-HA 966] (2x30 mg/kg, ip), given 30 min before dexfenfluramine (2x10 mg/kg, ip, 2 hourly) was also unable to prevent regional depletion of 5-HT, 5-HIAA, and 5-HTT density. However, ACEA 1021 (4x30 mg/kg, i.p.) given 30 min before (S)-3,4-methylenedioxymethamphetamine (MDMA, 4x10 mg/kg, 2 hourly, ip) attenuated the regional depletion of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-HT, 5-HIAA content, and 5-HTT density. ACEA 1021 combined with (S)-MDMA also prevented (S)-MDMA-induced hyperthermia without causing hypothermia or preventing an (S)-MDMA-induced increase in locomotor activity.


Asunto(s)
Temperatura Corporal/efectos de los fármacos , Dexfenfluramina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Proteínas de Transporte de Membrana , Actividad Motora/efectos de los fármacos , N-Metil-3,4-metilenodioxianfetamina/farmacología , Proteínas del Tejido Nervioso , Síndromes de Neurotoxicidad/psicología , Pirrolidinonas/farmacología , Quinoxalinas/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Agonistas de Receptores de Serotonina/farmacología , Animales , Autorradiografía , Química Encefálica/efectos de los fármacos , Proteínas Portadoras/metabolismo , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Masculino , Glicoproteínas de Membrana/metabolismo , Ratas , Ratas Wistar , Serotonina/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Estereoisomerismo , Telemetría
5.
Ann N Y Acad Sci ; 914: 208-14, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11085322

RESUMEN

3,4-Methylenedioxymethamphetamine (MDMA) and fenfluramine are amphetamine analogues that both cause long-term depletion of serotonin (5-HT) and 5-HT uptake sites in brain tissue. Depletion caused by these amphetamines is commonly measured by labeling 5-HT uptake sites using 3H-paroxetine combined with autoradiography or, alternatively measuring the concentration of 5-HT in tissue using high-performance liquid chromatography (HPLC). A close correlation between the 5-HT concentration measured in micropunch samples and the density of 3H-paroxetine-labeled 5-HT uptake sites measured in corresponding 20 micron coronal slices was determined (R2 = 0.92). These methods combined demonstrated that the glycine-site specific NMDA antagonist ACEA 1021 (4 x 30 mg/kg, i.p., 2 hourly) given 30 minutes before (S)-MDMA (4 x 10 mg/kg, i.p., 2 hourly) was able to prevent the depletion of both 5-HT content and uptake site density but unable to prevent the depletion of 5-HT content and uptake site density caused dexfenfluramine (4 x 15 mg/kg, i.p., 2 hourly).


Asunto(s)
Encéfalo/efectos de los fármacos , Dexfenfluramina/farmacología , N-Metil-3,4-metilenodioxianfetamina/farmacología , Fármacos Neuroprotectores/farmacología , Quinoxalinas/farmacología , Serotoninérgicos/farmacología , Serotonina/metabolismo , Animales , Animales Recién Nacidos , Encéfalo/anatomía & histología , Encéfalo/metabolismo , Química Encefálica/efectos de los fármacos , Interacciones Farmacológicas , Masculino , Paroxetina/farmacocinética , Ratas , Ratas Sprague-Dawley , Serotonina/farmacocinética , Tritio/farmacocinética
6.
Pharmacol Biochem Behav ; 51(2-3): 375-8, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7667356

RESUMEN

The stimulus properties of aminorex and analogues of 4-methylaminorex, namely (4S,5S)-4-methylaminorex, N-methyl-(4S,5S)-4-methylaminorex, and the regioisomeric (R)- and (S)-2-amino-4-phenyl-2-oxazoline (rexamino) were compared in rats trained to distinguish (S)-amphetamine (1 mg/kg) from saline. The first three compounds, aminorex, (4S,5S)-4-methylaminorex, and N-methyl-(4S,5S)-4-methylaminorex shared discriminative stimulus effects with amphetamine, although the stimulus properties for racemic aminorex were less than those of the other two compounds. The two regioisomers, (R)- and (S)-rexamino, produced only partial generalisation to the amphetamine.


Asunto(s)
Estimulantes del Sistema Nervioso Central/farmacología , Discriminación en Psicología/efectos de los fármacos , Drogas Ilícitas/farmacología , Oxazoles/farmacología , Anfetamina/farmacología , Animales , Condicionamiento Operante/efectos de los fármacos , Aprendizaje Discriminativo/efectos de los fármacos , Femenino , Generalización del Estimulo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Esquema de Refuerzo , Estereoisomerismo
11.
Appl Opt ; 8(5): 971-3, 1969 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-20072357

RESUMEN

The maximum resolution in the images of a given object produced by the holographic method using a single record in which only one wave parameter is stored at each point on the wavefront is shown to be one-half as great as that which could be obtained without any increase in the size or resolution capability of the recording if two parameters were recorded, the hologram being the aperture stop in each case. In lensless holography using plane reference waves for recording and reconstruction with a one-parameter hologram approximately equal to the object in size, the resolution is shown to be significantly less than the nominal photographic resolution of the recording medium.

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