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1.
Angle Orthod ; 90(6): 866-872, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-33378519

RESUMEN

OBJECTIVES: To test the hypotheses that mechanobehavior scores (MBS) were correlated with mandibular ramus lengths (Co-Go) and differed between facial phenotypes. MATERIALS AND METHODS: Subjects gave informed consent to participate. Co-Go (mm), mandibular plane angles (SN-GoGn, °), and three-dimensional anatomy were derived from cephalometric radiography or cone beam computed tomography. Temporomandibular joint (TMJ) energy densities (ED) (mJ/mm3) were measured using dynamic stereometry and duty factors (DF) (%) were measured from electromyography, to calculate MBS (= ED2 × DF,) for each TMJ. Polynomial regressions, K-means cluster analysis, and analysis of variance (ANOVA) with Tukey post-hoc tests were employed. RESULTS: Fifty females and 23 males produced replete data. Polynomial regressions showed MBS were correlated with Co-Go (females, R2 = 0.57; males, R2 = 0.81). Cluster analysis identified three groups (P < .001). Dolichofacial subjects, with shorter normalized Co-Go, clustered into two subgroups with low and high MBS compared to brachyfacial subjects with longer Co-Go. SN-GoGn was significantly larger (P < .03) in the dolichofacial subgroups combined (33.0 ± 5.9°) compared to the brachyfacial group (29.8 ± 5.5°). CONCLUSIONS: MBS correlated with Co-Go within sexes and differed significantly between brachyfacial and dolichofacial subjects.


Asunto(s)
Cara , Mandíbula , Cefalometría , Cara/anatomía & histología , Cara/diagnóstico por imagen , Femenino , Humanos , Masculino , Mandíbula/diagnóstico por imagen , Fenotipo , Articulación Temporomandibular
2.
Odontology ; 108(2): 321-330, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31912371

RESUMEN

The aim of this study was to investigate the effect of mechanical vibratory stimulation on maxillary canine retraction and pain perception in adolescents undergoing full-fixed orthodontic treatment with extraction. A pilot randomized-controlled clinical trial was conducted in one university orthodontic clinic. Twenty-one healthy adolescents who underwent full-fixed orthodontic treatment with maxillary first-premolar extraction were recruited. Subjects were randomly assigned to the experimental group (N = 10) that used a mechanical vibration device (AcceleDent Aura, OrthoAccel Technologies, Inc.) or the control group (N = 11) that did not receive a vibration device. The evaluation timepoints were T0 = day of initial canine retraction; T1 = 4 weeks post-initiation; T2 = 8 weeks post-initiation; and T3 = 12 weeks post-initiation. Three-dimensional palatal landmark superimpositions were made to assess amount of tooth movement (mm) at each visit, monthly rate of tooth movement (mm), and perceived pain levels (VAS scores). The total amount of tooth movement was observed in the control versus experimental groups, respectively, as 1.12 ± 0.22 mm versus 1.39 ± 0.36 mm at 4 weeks (p = 0.058), 2.59 ± 0.37 mm versus 2.49 ± 0.76 mm at 8 weeks (p = 0.702), and 3.54 ± 0.23 mm versus 3.37 ± 1.37 mm at 12 weeks (p = 0.716). The rate of tooth movement was 1.21 ± 0.32 mm/month in the control and 1.12 ± 0.20 mm/month in the experimental groups, which was not statistically significant at any of the timepoints and neither was the level of pain. This study found no statistically significant differences in canine retraction and pain perception between the experimental and control groups. We propose that further optimization of accelerated tooth movement with mechanical vibration devices is necessary.


Asunto(s)
Diente Canino , Vibración , Adolescente , Diente Premolar , Humanos , Dolor , Técnicas de Movimiento Dental
3.
Am J Orthod Dentofacial Orthop ; 156(1): 13-28.e1, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31256826

RESUMEN

The Board of Trustees of the American Association of Orthodontists asked a panel of medical and dental experts in sleep medicine and dental sleep medicine to create a document designed to offer guidance to practicing orthodontists on the suggested role of the specialty of orthodontics in the management of obstructive sleep apnea. This White Paper presents a summary of the Task Force's findings and recommendations.


Asunto(s)
Ortodoncia/métodos , Ortodoncia/normas , Ortodoncistas , Apnea Obstructiva del Sueño/terapia , Academias e Institutos , Humanos , Aparatos Ortodóncicos , Médicos , Polisomnografía/métodos , Prevalencia , Radiografía Dental , Factores de Riesgo , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/etiología , Cirujanos , Resultado del Tratamiento , Estados Unidos
4.
Orthod Craniofac Res ; 22 Suppl 1: 36-42, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31074130

RESUMEN

OBJECTIVES: The aim of this study was to compare three-dimensional airway changes resulting from mandibular advancement surgery and mandibular advancement surgery with constriction. SETTING AND SAMPLE POPULATION: The University of Michigan School of Dentistry and Medical Center. A total of 42 patients undergoing mandibular advancement with or without simultaneous constriction. MATERIALS AND METHODS: A retrospective airway evaluation of patients undergoing mandibular advancement with or without simultaneous mandibular constriction was performed. Cross-sectional evaluation at standardized locations, minimum cross section and volumetric analysis were performed using Dolphin Imaging TM Version 11.7. RESULTS: Patients undergoing mandibular advancement with or without constriction experienced significant airway increases (P < 0.05). Patients who underwent mandibular advancement only gained nearly twice as much airway volume as mandibular advancement with simultaneous constriction (8.69 mm3 vs 4.3 mm3 ). The largest increase for both groups was observed in the minimum axial area in the oropharynx segment (119.5 mm2 ) and the axial area of the retroglossal region (137.2 mm2 ). CONCLUSIONS: The findings demonstrate mandibular advancement with constriction results in airway enlargement following surgery.


Asunto(s)
Avance Mandibular , Faringe , Tomografía Computarizada de Haz Cónico , Constricción , Estudios Transversales , Estudios de Seguimiento , Humanos , Imagenología Tridimensional , Estudios Retrospectivos
5.
Orthod Craniofac Res ; 22 Suppl 1: 30-35, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31074136

RESUMEN

INTRODUCTION: The aim of this study was to determine the 3D airway changes that occur following mandibular setback surgery alone vs bimaxillary surgery in patients with similar skeletal start forms. SETTING AND SAMPLE POPULATION: The University of Michigan School of Dentistry and Medical Center. A total of 85 patients undergoing mandibular setback with or without simultaneous maxillary advancement. MATERIALS AND METHODS: A retrospective evaluation of pre- and post-surgical CBCT scans for patients undergoing mandibular setback surgery alone (14) vs bimaxillary surgery (71) was performed. Cross-sectional evaluation at standardized locations, minimum cross section and volumetric analysis were performed (Dolphin Imaging & Management Solutions). RESULTS: Patients who underwent mandibular setback surgery alone showed a statistically significant average increase of 47.5 mm2 in minimum axial area. Patients who underwent bimaxillary surgery showed a statistically significant increase in airway volume, minimum axial area, location of minimum axial area, and axial area at the retropalatal and retroglossal regions. CONCLUSIONS: The results demonstrate that the mandible can be setback safely without decreasing airway dimensions. In borderline OSA patients, bimaxillary surgery remains the preferred approach due to the larger airway increases observed. Long-term follow-up with polysomnography must be conducted to determine the full functional implications of both procedures.


Asunto(s)
Maloclusión de Angle Clase III , Procedimientos Quirúrgicos Ortognáticos , Tomografía Computarizada de Haz Cónico Espiral , Tomografía Computarizada de Haz Cónico , Estudios Transversales , Humanos , Mandíbula , Avance Mandibular , Faringe , Estudios Retrospectivos
6.
Angle Orthod ; 89(1): 138-148, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29799273

RESUMEN

Class III open bite malocclusion can be among the most difficult case types to obtain an excellent occlusal, skeletal, and facial outcome. Treatment options include growth modification, extraction for orthodontic camouflage, and orthognathic surgery. For the most severely affected and non-growing patients, orthognathic surgery is often the most predictable and, in some situations, the only viable way of achieving an optimal result. The risks and benefits of surgical treatment options can occasionally be difficult to assess particularly for providers with limited experience. Two-dimensional surgical predictions can assist but do not permit the third dimension to be visualized. New techniques of computer-aided surgical simulation can enable the surgeon, orthodontist, and patient to better visualize and understand the treatment approach and enable them to make the most effective and efficient treatment related decisions. This case merges knowledge of the full spectrum of historical surgical techniques with the new approach of computer-aided surgical simulation (CASS) to perform complex segmental maxillary and mandibular surgery to obtain an excellent functional and esthetic result.


Asunto(s)
Maloclusión de Angle Clase III , Procedimientos Quirúrgicos Ortognáticos , Adulto , Cefalometría , Estética Dental , Humanos , Maloclusión de Angle Clase III/cirugía , Mandíbula , Maxilar/cirugía , Resultado del Tratamiento
8.
Am J Orthod Dentofacial Orthop ; 149(5): 729-39, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27131255

RESUMEN

Asymmetries are among the most challenging problems in orthodontics. Proper diagnosis is critical to discern first whether the asymmetry is dental or skeletal. If it is dental, one must then determine whether one dental arch or both are at fault. Once diagnosed, the next challenge is determining not only an appropriate treatment plan, but also the appropriate mechanics plan. This aim of this article is to present a patient with a severe asymmetry to emphasize the importance of a problem-based differential diagnosis to develop both a sound treatment plan and a mechanics plan that successfully integrates miniscrews from the start of the process. An 18-year-old woman had a Class III subdivision left malocclusion, an asymmetric lower facial third, and a deviated midline. The treatment plan consisted of asymmetric distalization of the maxillary right and mandibular left posterior dentitions to create space to resolve the deviated midlines, correct the canted occlusal plane, and obtain an ideal occlusion. Active treatment with Clarity ceramic 0.022 × 0.028-in appliances (3M Unitek, Monrovia, Calif), temporary anchorage devices, and a pendulum appliance lasted 22 months. The final result and the 2-year retention records demonstrate that a harmonious facial balance, an attractive smile, ideal occlusal relationships, and a stable outcome were achieved. This case report shows that with proper planning, asymmetric use of temporary anchorage devices in multiple posterior quadrants can be used to obtain molar distalization, and this approach is an effective alternative to dental extraction therapy.


Asunto(s)
Maloclusión de Angle Clase III/terapia , Aparatos Ortodóncicos , Técnicas de Movimiento Dental/métodos , Adolescente , Tornillos Óseos , Femenino , Humanos , Maloclusión de Angle Clase III/patología , Diente Molar , Índice de Severidad de la Enfermedad
9.
Orthod Craniofac Res ; 18 Suppl 1: 83-90, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25865536

RESUMEN

With so many disciplines of both medicine and dentistry involved in the treatment of obstructive sleep apnea (OSA), several forms of therapy are available. The orthodontist is rarely considered when the diagnosis of chronic obstructive sleep apnea (OSA) is delivered. However, the scope of orthodontic care today is much broader than the mere alignment of teeth. While the current gold standard for OSA care remains continuous positive air pressure (CPAP), the patient may be given a prescription for an intra-oral sleep appliance. When orthodontists work in concert with their medical colleagues to provide a sleep appliance, several considerations must be made including the evidence regarding oral appliance efficacy. For some patients, oral appliances are highly successful; however, even for responsive patients, there are risks associated with oral appliance therapy. The aim of the paper was to present a critical review of the current level of evidence for the use of oral appliances in the treatment of OSA. A substantial number of publications ranging from case reports, uncontrolled and controlled case series, prospective randomized studies, and even a small number of systematic reviews were available. The existing systematic reviews were based on either a limited number of prospective studies with limited numbers of patients or in some cases were based on subjective data only. As a result, a narrative review of the literature was performed that discusses objective clinically testable criteria and recent developments that may aid future research investigations.


Asunto(s)
Aparatos Ortodóncicos , Apnea Obstructiva del Sueño/terapia , Humanos , Avance Mandibular/instrumentación , Diseño de Aparato Ortodóncico , Faringe/patología
10.
J Synchrotron Radiat ; 22(2): 336-41, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25723934

RESUMEN

Hard X-ray microscopy is a prominent tool suitable for nanoscale-resolution non-destructive imaging of various materials used in different areas of science and technology. With an ongoing effort to push the 2D/3D imaging resolution down to 10 nm in the hard X-ray regime, both the fabrication of nano-focusing optics and the stability of the microscope using those optics become extremely challenging. In this work a microscopy system designed and constructed to accommodate multilayer Laue lenses as nanofocusing optics is presented. The developed apparatus has been thoroughly characterized in terms of resolution and stability followed by imaging experiments at a synchrotron facility. Drift rates of ∼2 nm h(-1) accompanied by 13 nm × 33 nm imaging resolution at 11.8 keV are reported.

11.
Rev Sci Instrum ; 86(12): 123702, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26724037

RESUMEN

We present a modulation transfer function (MTF) calibration method based on binary pseudo-random (BPR) one-dimensional sequences and two-dimensional arrays as an effective method for spectral characterization in the spatial frequency domain of a broad variety of metrology instrumentation, including interferometric microscopes, scatterometers, phase shifting Fizeau interferometers, scanning and transmission electron microscopes, and at this time, x-ray microscopes. The inherent power spectral density of BPR gratings and arrays, which has a deterministic white-noise-like character, allows a direct determination of the MTF with a uniform sensitivity over the entire spatial frequency range and field of view of an instrument. We demonstrate the MTF calibration and resolution characterization over the full field of a transmission soft x-ray microscope using a BPR multilayer (ML) test sample with 2.8 nm fundamental layer thickness. We show that beyond providing a direct measurement of the microscope's MTF, tests with the BPRML sample can be used to fine tune the instrument's focal distance. Our results confirm the universality of the method that makes it applicable to a large variety of metrology instrumentation with spatial wavelength bandwidths from a few nanometers to hundreds of millimeters.

12.
Am J Orthod Dentofacial Orthop ; 146(2): 238-48, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25085307

RESUMEN

A young man, age 18 years 4 months, with a concave profile, a skeletal maxillary deficiency, and a severe alveolar cleft with an unesthetic appearance of the maxillary anterior teeth was referred for orthodontic treatment. After a detailed review of his pretreatment records, both surgical and nonsurgical treatment plans were presented to the patient, who opted for a nonsurgical interdisciplinary approach. His complex 3-dimensional malocclusion required palatal expansion, dental extractions, and periodontal and prosthodontic consultations and treatment, in addition to comprehensive orthodontic therapy. MBT (Xinya, HangZhou, China) 0.022 × 0.028-in appliances combined with a mini-implant to enhance the orthodontic anchorage were used to level, align, and establish a Class I relationship. After the orthodontic treatment, a combined restorative and periodontal approach was used to enhance the patient's esthetic and functional outcomes. Both the final result and the 1-year follow-up records demonstrate that the treatment goals of establishing proper occlusion, normal function, a balanced profile, better esthetics, and a stable outcome were achieved. The purpose of this case report is to demonstrate that an interdisciplinary treatment protocol can significantly improve the transverse discrepancies and achieve a satisfactory occlusion with a balanced profile in patients with cleft lip and palate.


Asunto(s)
Labio Leporino/terapia , Fisura del Paladar/terapia , Maloclusión de Angle Clase III/terapia , Planificación de Atención al Paciente , Grupo de Atención al Paciente , Adolescente , Proceso Alveolar/anomalías , Proceso Alveolar/patología , Diente Premolar/patología , Cefalometría/métodos , Coronas , Arco Dental/patología , Estudios de Seguimiento , Enfermedades de las Encías/terapia , Humanos , Incisivo/patología , Masculino , Maxilar/anomalías , Maxilar/patología , Diseño de Aparato Ortodóncico , Técnica de Expansión Palatina/instrumentación , Erupción Ectópica de Dientes/terapia , Extracción Dental , Técnicas de Movimiento Dental/instrumentación , Resultado del Tratamiento
13.
Rev Sci Instrum ; 85(3): 033707, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24689592

RESUMEN

We have designed and constructed a dedicated instrument to perform ptychography measurements and characterization of multilayer Laue lenses nanofocusing optics. The design of the scanning microscope provides stability of components and minimal thermal drifts, requirements for nanometer scale spatial resolution measurements. We performed thorough laboratory characterization of the instrument in terms of resolution and thermal drifts with subsequent measurements at a synchrotron. We have successfully acquired and reconstructed ptychography data yielding 11 nm line focus.

14.
Phys Rev Lett ; 107(21): 212501, 2011 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-22181874

RESUMEN

We report the observation of two-neutrino double-beta decay in (136)Xe with T(1/2) = 2.11 ± 0.04(stat) ± 0.21(syst) × 10(21) yr. This second-order process, predicted by the standard model, has been observed for several nuclei but not for (136)Xe. The observed decay rate provides new input to matrix element calculations and to the search for the more interesting neutrinoless double-beta decay, the most sensitive probe for the existence of Majorana particles and the measurement of the neutrino mass scale.

15.
Rev Sci Instrum ; 82(10): 105114, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22047336

RESUMEN

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon time projection chamber of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute of xenon gas with 750 Torr differential pressure.

16.
Dentomaxillofac Radiol ; 40(1): 24-34, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21159912

RESUMEN

Cone beam CT (CBCT) has become an increasingly important source of three dimensional (3D) volumetric data in clinical orthodontics since its introduction into dentistry in 1998. The purpose of this manuscript is to highlight the current understanding of, and evidence for, the clinical use of CBCT in orthodontics, and to review the findings to answer clinically relevant questions. Currently available information from studies using CBCT can be organized into five broad categories: 1, the assessment of CBCT technology; 2, its use in craniofacial morphometric analyses; 3, incidental and missed findings; 4, analysis of treatment outcomes; and 5, efficacy of CBCT in diagnosis and treatment planning. The findings in these topical areas are summarized, followed by current indications and protocols for the use of CBCT in specific cases. Despite the increasing popularity of CBCT in orthodontics, and its advantages over routine radiography in specific cases, the effects of information derived from these images in altering diagnosis and treatment decisions has not been demonstrated in several types of cases. It has therefore been recommended that CBCT be used in select cases in which conventional radiography cannot supply satisfactory diagnostic information; these include cleft palate patients, assessment of unerupted tooth position, supernumerary teeth, identification of root resorption and for planning orthognathic surgery. The need to image other types of cases should be made on a case-by-case basis following an assessment of benefits vs risks of scanning in these situations.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Ortodoncia/métodos , Cefalometría/métodos , Fisura del Paladar/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/estadística & datos numéricos , Humanos , Maloclusión/diagnóstico por imagen , Evaluación de Resultado en la Atención de Salud , Planificación de Atención al Paciente , Selección de Paciente , Dosis de Radiación , Resorción Radicular/diagnóstico por imagen , Evaluación de la Tecnología Biomédica , Articulación Temporomandibular/diagnóstico por imagen , Diente no Erupcionado/diagnóstico por imagen
17.
J Oral Rehabil ; 38(2): 136-56, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20722775

RESUMEN

Until recently, obstructive sleep apnoea was a largely unknown condition. Because of the well-publicised death of some high-profile people resulting from untreated obstructive sleep apnoea, now mostly everyone has heard of the condition. Following diagnosis, several medical treatment modalities are available to patients. However, the role that dentistry and its various specialties can play in successful treatment for obstructive sleep apnoea should not be overlooked. The common causes for adult and paediatric obstructive sleep apnoea will be presented as well as a review of the more successful forms of dental treatment. Finally, a summary of the current evidence regarding obstructive sleep apnoea treatment will be presented.


Asunto(s)
Apnea Obstructiva del Sueño/terapia , Adolescente , Adulto , Cefalometría , Niño , Tomografía Computarizada de Haz Cónico , Presión de las Vías Aéreas Positiva Contínua , Humanos , Imagen por Resonancia Magnética , Obesidad/complicaciones , Ferulas Oclusales , Ortodoncia Interceptiva , Procedimientos Quirúrgicos Ortognáticos , Técnica de Expansión Palatina , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/etiología
18.
Psychol Med ; 41(6): 1291-300, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20925971

RESUMEN

BACKGROUND: Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response. METHOD: Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine. RESULTS: Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified. CONCLUSIONS: This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.


Asunto(s)
Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Psicología del Esquizofrénico , Adolescente , Adulto , Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Olanzapina , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Psicometría , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/psicología , Risperidona/efectos adversos , Esquizofrenia/diagnóstico , Adulto Joven
19.
Pharmacogenomics J ; 9(5): 311-8, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19451915

RESUMEN

Clinical trial data were evaluated for the association between 22 single-nucleotide polymorphisms (SNPs) and response in acutely ill patients diagnosed with schizophrenia, schizoaffective disorder or schizophreniform disorder, who were treated with oral risperidone. All patients in the exploratory (78 African Americans) and validation (65 whites) data sets received risperidone 2-6 mg per day over 2-12 weeks. Two SNPs were found to have significant associations with response to risperidone over 2-12 weeks in both African-American and white patients and had a consistent direction of effect in both cohorts. Metabotropic glutamate receptor (GRM3) SNP, rs724226, was associated with a change in the positive and negative syndrome scale (PANSS) total response. Catechol-O-methyltransferase (COMT) SNP, rs165599, was moderately associated with a change in the PANSS Negative score. The greater prevalence of poor-responder GRM3 and COMT alleles in white versus African-American patients might have a clinical significance in evaluating the ethnic-specific response to risperidone.


Asunto(s)
Antipsicóticos/uso terapéutico , Negro o Afroamericano/genética , Catecol O-Metiltransferasa/genética , Polimorfismo de Nucleótido Simple , Receptores de Glutamato Metabotrópico/genética , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Población Blanca/genética , Administración Oral , Adulto , Antipsicóticos/administración & dosificación , Método Doble Ciego , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética , Escalas de Valoración Psiquiátrica , Risperidona/administración & dosificación , Esquizofrenia/etnología , Esquizofrenia/genética , Psicología del Esquizofrénico , Factores de Tiempo , Resultado del Tratamiento
20.
Mol Psychiatry ; 13(5): 498-506, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-17622221

RESUMEN

Considerable attention has focused on regulation of central tryptophan hydroxylase (TPH) activity and protein expression. At the time of these earlier studies, it was thought that there was a single central TPH isoform. However, with the recent identification of TPH2, it becomes important to distinguish between regulatory effects on the protein expression and activity of the two isoforms. We have generated a TPH2-specific polyclonal antiserum (TPH2-6361) to study regulation of TPH2 at the protein level and to examine the distribution of TPH2 expression in rodent and human brain. TPH2 immunoreactivity (IR) was detected throughout the raphe nuclei, in lateral hypothalamic nuclei and in the pineal body of rodent and human brain. In addition, a prominent TPH2-IR fiber network was found in the human median eminence. We recently reported that glucocorticoid treatment of C57/Bl6 mice for 4 days markedly decreased TPH2 messenger RNA levels in the raphe nuclei, whereas TPH1 mRNA was unaffected. The glucocorticoid-elicited inhibition of TPH2 gene expression was blocked by co-administration of the glucocorticoid receptor antagonist mifepristone (RU-486). Using TPH2-6361, we have extended these findings to show a dose-dependent decrease in raphe TPH2 protein levels in response to 4 days of treatment with dexamethasone; this effect was blocked by co-administration of mifepristone. Moreover, the glucocorticoid-elicited inhibition of TPH2 was functionally significant: serotonin synthesis was significantly reduced in the frontal cortex of glucocorticoid-treated mice, an effect that was blocked by mifepristone co-administration. This study provides further evidence for the glucocorticoid regulation of serotonin biosynthesis via inhibition of TPH2 expression, and suggest that elevated glucocorticoid levels may be relevant to the etiology of psychiatric diseases, such as depression, where hypothalamic-pituitary-adrenal axis dysregulation has been documented.


Asunto(s)
5-Hidroxitriptófano/biosíntesis , Dexametasona/análogos & derivados , Lóbulo Frontal/química , Proteínas del Tejido Nervioso/biosíntesis , Núcleos del Rafe/enzimología , Triptófano Hidroxilasa/análisis , Triptófano Hidroxilasa/biosíntesis , 5-Hidroxitriptófano/análisis , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos , Dexametasona/farmacología , Inducción Enzimática/efectos de los fármacos , Femenino , Lóbulo Frontal/efectos de los fármacos , Humanos , Sueros Inmunes , Ratones , Ratones Endogámicos C57BL , Mifepristona/farmacología , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/inmunología , Ovariectomía , Fragmentos de Péptidos/inmunología , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , ARN Mensajero/biosíntesis , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Triptófano Hidroxilasa/genética , Triptófano Hidroxilasa/inmunología
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