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1.
Nervenarzt ; 88(1): 26-33, 2017 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-27853854

RESUMO

With each additional accumulative exposure to severe and traumatic stressors, the likelihood of developing mental health problems and physical diseases increases. Displaced individuals have usually experienced a number of serious threats to health due to organized violence in their home country or attacks during the flight. Frequently, domestic violence adds additional strain to the stressors experienced. The resulting impairments in psychosocial functioning reduce the resources needed for social adjustment and integration. Social exclusion then in turn often further aggravates the existing mental health complications. For the treatment of trauma spectrum disorders, different evidence-based psychotherapies are available. In high-income countries, trained and licensed psychotherapists are typically in positions to apply such interventions; however, even an advanced system with a high capacity, such as the psychotherapeutic care offered in Germany, severely struggles to manage the demands associated with the rapid addition of hundreds of thousands of displaced people. Germany's mental healthcare system at present lacks the resources, both human and technological, to effectively manage the present demands. Systematic scientific studies in resource-poor regions of war and conflict have demonstrated that the dissemination of effective treatment to local personnel, even with limited training, results in substantial improvements in the mental health challenges within the community: Organized as a cascade model, members of the refugee community learn to identify weakened fellow citizens requiring in-depth diagnostic interviews. Educated, bilingual individuals acquainted with their country's healthcare system (e. g. nurses, teachers and social workers) receive training to conduct structured interviews and evidence-based interventions under the supervision of centrally organized licensed psychotherapists. More complex cases are referred to local psychotherapists, psychiatrists or specialized treatment centers. These humanitarian efforts are based on the convention for the protection of human rights and secure the safety, freedom and dignity of these persons.


Assuntos
Programas de Rastreamento/métodos , Educação de Pacientes como Assunto/métodos , Psicoterapia/educação , Refugiados/psicologia , Apoio Social , Transtornos de Estresse Traumático/terapia , Barreiras de Comunicação , Humanos , Disseminação de Informação/métodos , Psicoterapia/métodos , Transtornos de Estresse Traumático/diagnóstico , Transtornos de Estresse Traumático/psicologia , Resultado do Tratamento , Guerra
2.
Nervenarzt ; 85(3): 356-62, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23695004

RESUMO

Stressful war experiences can cause posttraumatic stress disorder (PTSD) in survivors. To what extent were the soldiers and young women of World War II affected by PTSD symptoms over the course of their lives? Do these men and women differ in the traumatic experiences and PTSD symptom severity? To investigate these questions 52 male and 20 female Germans aged 81-95 years were recruited through newspaper advertisements and notices and interviewed regarding war experiences and PTSD symptoms. Of the men 2% and 7% met the criteria for current and lifetime PTSD diagnoses, respectively, as compared to 10% and 30% of the women, respectively. Using multiple linear regression a dose-response relationship between the number of trauma types experienced and PTSD symptom severity could be demonstrated. The slope of the regression curve was steeper for women than for men. When controlling for the number of different traumatic experiences women reported a significantly higher severity of PTSD symptoms than men. It is presumed that this difference in severity of symptoms can be attributed to qualitative differences in the type of traumatic stress factors during the war. The present study provides evidence that even today people continue to be affected by PTSD symptoms due to events which occurred during World War II; therefore, during patient contact with this age group the war experiences specific to each individual need to be considered as potential moderators of symptoms.


Assuntos
Militares/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Sobreviventes/estatística & dados numéricos , II Guerra Mundial , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/psicologia , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Militares/psicologia , Prevalência , Fatores de Risco , Distribuição por Sexo , Sobreviventes/psicologia
3.
Psychother Psychosom ; 80(6): 345-52, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21829046

RESUMO

BACKGROUND: The aim of the present randomized controlled trial was to compare the outcome of 2 active treatments for posttraumatic stress disorder (PTSD) as a consequence of war and torture: narrative exposure therapy (NET) and stress inoculation training (SIT). METHODS: Twenty-eight PTSD patients who had experienced war and torture, most of them asylum seekers, received 10 treatment sessions of either NET or SIT at the Outpatient Clinic for Refugees, University of Konstanz, Germany. Posttests were carried out 4 weeks after treatment, and follow-up tests were performed 6 months and 1 year after treatment. The main outcome measure was the PTSD severity score according to the Clinician-Administered PTSD Scale (CAPS) at each time point. RESULTS: A significant reduction in PTSD severity was found for NET, but not for SIT. A symptom reduction in the NET group occurred between pretest and the 6-month follow-up examination, the effect size being d = 1.42 (for SIT: d = 0.12), and between pretest and the 1-year follow-up, the effect size being d = 1.59 (for SIT: d = 0.19). The rates and scores of major depression and other comorbid disorders did not decrease significantly over time in either of the 2 treatment groups. CONCLUSIONS: The results indicate that exposure treatments like NET lead to a significant PTSD symptom reduction even in severely traumatized refugees and asylum seekers.


Assuntos
Terapia Implosiva/métodos , Refugiados/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Tortura , Guerra , Comorbidade , Seguimentos , Alemanha , Humanos , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Narração , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Tortura/psicologia , Resultado do Tratamento
4.
Science ; 270(5234): 305-7, 1995 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-7569982

RESUMO

Magnetic source imaging revealed that the cortical representation of the digits of the left hand of string players was larger than that in controls. The effect was smallest for the left thumb, and no such differences were observed for the representations of the right hand digits. The amount of cortical reorganization in the representation of the fingering digits was correlated with the age at which the person had begun to play. These results suggest that the representation of different parts of the body in the primary somatosensory cortex of humans depends on use and changes to conform to the current needs and experiences of the individual.


Assuntos
Dedos/inervação , Música , Plasticidade Neuronal , Neurônios Aferentes/fisiologia , Córtex Somatossensorial/fisiologia , Polegar/inervação , Adulto , Vias Aferentes , Envelhecimento , Mapeamento Encefálico , Humanos , Magnetoencefalografia , Estimulação Física , Córtex Somatossensorial/anatomia & histologia , Tato
5.
Prog Brain Res ; 166: 525-36, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17956816

RESUMO

There is widespread recognition that consistency between research centres in the ways that patients with tinnitus are assessed and outcomes following interventions are measured would facilitate more effective co-operation and more meaningful evaluations and comparisons of outcomes. At the first Tinnitus Research Initiative meeting held in Regensburg in July 2006 an attempt was made through workshops to gain a consensus both for patient assessments and for outcome measurements. It is hoped that this will contribute towards better cooperation between research centres in finding and evaluating treatments for tinnitus by allowing better comparability between studies.


Assuntos
Inquéritos e Questionários/normas , Zumbido/diagnóstico , Zumbido/terapia , Consenso , Humanos , Resultado do Tratamento
6.
J Affect Disord ; 218: 428-436, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28505586

RESUMO

BACKGROUND: Individuals with trauma-related disorders are complex and heterogeneous; part of this complexity derives from additional psychopathology like dissociation as well as environmental adversities such as traumatic stress, experienced throughout the lifespan. Understanding the neurophysiological abnormalities in Post-traumatic stress disorder (PTSD) requires a simultaneous consideration of these factors. METHODS: Resting state magnetoencephalography (MEG) recordings were obtained from 41 women with PTSD and comorbid depressive symptoms, and 16 healthy women. Oscillatory brain activity was extracted for five frequency bands and 11 source locations, and analyzed in relation to shutdown dissociation and adversity-related measures. RESULTS: Dissociative symptoms were related to increased delta and lowered beta power. Adversity-related measures modulated theta and alpha oscillatory power (in particular childhood sexual abuse) and differed between patients and controls. LIMITATIONS: Findings are based on women with comorbid depressive symptoms and therefore may not be applicable for men or groups with other clinical profiles. In respect to childhood adversities, we had no reliable source for the early infancy. CONCLUSION: Trauma-related abnormalities in neural organization vary with both exposure to adversities as well as their potential to evoke ongoing shutdown responses.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Transtornos Dissociativos/psicologia , Magnetoencefalografia/métodos , Traumatismo Múltiplo/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Comorbidade , Depressão/diagnóstico por imagem , Depressão/fisiopatologia , Depressão/psicologia , Transtornos Dissociativos/diagnóstico por imagem , Transtornos Dissociativos/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Traumatismo Múltiplo/fisiopatologia , Psicopatologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
7.
Transl Psychiatry ; 7(8): e1202, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28809857

RESUMO

Stress during pregnancy may impact subsequent generations, which is demonstrated by an increased susceptibility to childhood and adulthood health problems in the children and grandchildren. Although the importance of the prenatal environment is well reported with regards to future physical and emotional outcomes, little is known about the molecular mechanisms that mediate the long-term consequences of early stress across generations. Recent studies have identified DNA methylation as a possible mediator of the impact of prenatal stress in the offspring. Whether psychosocial stress during pregnancy also affects DNA methylation of the grandchildren is still not known. In the present study we examined the multigenerational hypothesis, that is, grandmaternal exposure to psychosocial stress during pregnancy affecting DNA methylation of the grandchildren. We determined the genome-wide DNA methylation profile in 121 children (65 females and 56 males) and tested for associations with exposure to grandmaternal interpersonal violence during pregnancy. We observed methylation variations of five CpG sites significantly (FDR<0.05) associated with the grandmother's report of exposure to violence while pregnant with the mothers of the children. The results revealed differential methylation of genes previously shown to be involved in circulatory system processes (FDR<0.05). This study provides support for DNA methylation as a biological mechanism involved in the transmission of stress across generations and motivates further investigations to examine prenatal-dependent DNA methylation as a potential biomarker for health problems.


Assuntos
Metilação de DNA , Epigênese Genética , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/genética , Estresse Psicológico/genética , Adolescente , Criança , Ilhas de CpG , Estudos Transversais , Exposição à Violência/psicologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Mães , Gravidez
8.
J Neurosci ; 20(1): 446-50, 2000 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-10627620

RESUMO

Maps of the body surface in somatosensory cortex have been shown to be highly plastic, altering their configuration in response to changes in use of body parts. The current study investigated alterations in the functional organization of the human somatosensory cortex resulting from massed practice. Over a period of 4 weeks, subjects were given synchronous tactile stimulation of thumb (D1) and little finger (D5) for 1 hr/d. They had to identify the orientation of the stimuli. Neuroelectric source localization based on high-resolution EEG revealed that, when subjects received passive tactile stimulation of D1 or D5, the representations of the fingers in primary somatosensory cortex were closer together after training than before. There was also an apparently correlative tendency to anomalously mislocalize near-threshold tactile stimuli equally to the distant finger costimulated during training rather than preferentially to the finger nearest to the finger stimulated in a post-training test. However, when the stimulus discrimination had to be made, neuroelectric source imaging revealed that the digital representations of D1 and D5 were further apart after training than before. Thus, the same series of prolonged repetitive stimulations produced two different opposite effects on the spatial relationship of the cortical representations of the digits, suggesting that differential activation in the same region of somatosensory cortex is specific to different tasks.


Assuntos
Aprendizagem por Discriminação/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Plasticidade Neuronal/fisiologia , Córtex Somatossensorial/fisiologia , Adulto , Feminino , Dedos/fisiologia , Humanos , Masculino , Tempo de Reação/fisiologia , Limiar Sensorial/fisiologia , Tato/fisiologia
9.
J Neurosci ; 19(16): 7152-61, 1999 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10436068

RESUMO

Neuronal oscillations in the gamma band (above 30 Hz) have been proposed to be a possible mechanism for the visual representation of objects. The present study examined the topography of gamma band spectral power and event-related potentials in human EEG associated with perceptual switching effected by rotating ambiguous (bistable) figures. Eleven healthy human subjects were presented two rotating bistable figures: first, a face figure that allowed perception of a sad or happy face depending on orientation and therefore caused a perceptual switch at defined points in time when rotated, and, second, a modified version of the Rubin vase, allowing perception as a vase or two faces whereby the switch was orientation-independent. Nonrotating figures served as further control stimuli. EEG was recorded using a high-density array with 128 electrodes. We found a negative event-related potential associated with the switching of the sad-happy figure, which was most pronounced at central prefrontal sites. Gamma band activity (GBA) was enhanced at occipital electrode sites in the rotating bistable figures compared with the standing stimuli, being maximal at vertical stimulus orientations that allowed an easy recognition of the sad and happy face or the vase-faces, respectively. At anterior electrodes, GBA showed a complementary pattern, being maximal when stimuli were oriented horizontally. The findings support the notion that formation of a visual percept may involve oscillations in a distributed neuronal assembly.


Assuntos
Eletroencefalografia , Potenciais Evocados Visuais/fisiologia , Teoria Gestáltica , Percepção Visual/fisiologia , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Rotação
10.
Facial Plast Surg Clin North Am ; 13(1): 15-31, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15519925

RESUMO

Careful analysis of a rhytidectomy patient is an important aspect of facial plastic surgery. Surgeons and physicians are successful when they diagnose patients correctly and apply the correct treatment plan. The skilled facial plastic surgeon appropriately evaluates the patient physically and emotionally then performs the correct surgical maneuvers to achieve the desired results. The focus of this article is the senior author's 20 years of experience in analyzing faces, and the goal of this article is to assist surgeons in achieving postoperative patients who are happy and "natural looking."


Assuntos
Ritidoplastia/métodos , Envelhecimento da Pele , Humanos , Pescoço , Seleção de Pacientes
11.
Transl Psychiatry ; 5: e571, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-26080088

RESUMO

Stress, particularly when experienced early in life, can have profound implications for mental health. Previous research covering various tissues such as the brain, suggests that the detrimental impact of early-life stress (ELS) on mental health is mediated via epigenetic modifications including DNA methylation. Genes of the hypothalamic-pituitary-adrenal axis--in particular, the glucocorticoid receptor (hGR) gene--stand out as key targets for ELS. Even though the link between hGR methylation and either ELS or psychopathology is fairly well established, the mutually dependent relationships between ELS, DNA methylation and psychopathology remain to be uncovered. The specific psychopathology an individual might develop in the aftermath of stressful events can be highly variable, however, most studies investigating hGR methylation and psychopathology suffer from being limited to a single symptom cluster of mental disorders. Here, we screened volunteers for childhood maltreatment and analyzed whether it associates with hGR methylation in lymphocytes and a range of measures of psychological ill-health. hGR methylation in lymphocytes most likely reflects methylation patterns found in the brain and thus provides valuable insights into the etiology of psychopathology. We find the interaction between childhood maltreatment and hGR methylation to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions. Furthermore, our results indicate an additive effect of childhood maltreatment and hGR methylation in predicting borderline personality disorder (BPD)-associated symptoms, suggesting that the combination of both ELS and DNA methylation that possibly represents unfavorable events experienced even earlier in life poses the risk for BPD.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/psicologia , Metilação de DNA , Interação Gene-Ambiente , Transtornos Mentais/genética , Receptores de Glucocorticoides/genética , Adolescente , Ansiedade/genética , Ansiedade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/genética , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtorno da Personalidade Borderline/genética , Transtorno da Personalidade Borderline/psicologia , Criança , Estudos de Coortes , Depressão/genética , Depressão/psicologia , Epigênese Genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Transtornos Mentais/psicologia , Adulto Jovem
12.
Stroke ; 32(7): 1621-6, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11441210

RESUMO

Patients with chronic aphasia were assigned randomly to a group to receive either conventional aphasia therapy or constraint-induced (CI) aphasia therapy, a new therapeutic technique requiring intense practice over a relatively short period of consecutive days. CI aphasia therapy is realized in a communicative therapeutic environment constraining patients to practice systematically speech acts with which they have difficulty. Patients in both groups received the same amount of treatment (30 to 35 hours) as 10 days of massed-practice language exercises for the CI aphasia therapy group (3 hours per day minimum; 10 patients) or over a longer period of approximately 4 weeks for the conventional therapy group (7 patients). CI aphasia therapy led to significant and pronounced improvements on several standard clinical tests, on self-ratings, and on blinded-observer ratings of the patients' communicative effectiveness in everyday life. Patients who received the control intervention failed to achieve comparable improvements. Data suggest that the language skills of patients with chronic aphasia can be improved in a short period by use of an appropriate massed-practice technique that focuses on the patients' communicative needs.


Assuntos
Afasia/terapia , Fonoterapia , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Afasia/complicações , Afasia/diagnóstico , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Biol Psychiatry ; 32(7): 595-606, 1992 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-1450286

RESUMO

Physical and dynamic aspects of the electroencephalogram (EEG) were evaluated in 12 schizophrenic patients and 12 matched healthy control subjects by means of two descriptive measures proposed by Hjorth (complexity and mobility) and by a nonlinear measure, dimensional complexity. These measures were compared to power spectra analyses. EEG was recorded from frontal, central, and parietal leads under resting conditions (eyes open and eyes closed) for 12 epochs each of 25 sec. Patients showed the expected increased activity in the 1-7 Hz band and, furthermore, a scalp distribution of dimensional complexity and Hjorth complexity opposite to the distribution in controls: in patients dimensional complexity yielded higher values at frontal (Fz) than central (Cz) leads, whereas the resemblance to sinusoidal waveshape (Hjorth complexity) was larger at Fz than Cz. Results indicate more dynamic complexity or variables determining the dynamics of brain processes in frontal areas in patients.


Assuntos
Córtex Cerebral/fisiopatologia , Eletroencefalografia/instrumentação , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Processamento de Sinais Assistido por Computador/instrumentação , Adulto , Algoritmos , Ritmo alfa , Nível de Alerta/fisiologia , Atenção/fisiologia , Mapeamento Encefálico/instrumentação , Gráficos por Computador , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico
14.
Biol Psychiatry ; 50(2): 108-16, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11526991

RESUMO

BACKGROUND: Schizophrenic patients exhibit more activity in the electroencephalographic delta and theta frequency range than do control subjects. Using magnetic source imaging (MSI) our study aimed to explore this phenomenon in the magnetoencephalogram (MEG), the distribution of its sources, and associations between symptom profiles and sources of low-frequency activity in the brain. METHODS: Whole-head MEG recordings were obtained from 28 schizophrenic patients and 20 healthy control subjects during a resting condition. The generators of the focal magnetic slow waves were located employing a single moving dipole model. Distributed or multiple delta and theta sources were captured by the minimum norm estimate. RESULTS: Both localization procedures showed slow wave activity to be enhanced in schizophrenic patients compared with control subjects. Focal slow wave activity differed most between groups in frontotemporal and in posterior regions. Slow wave activity was associated with symptom characteristics in that positive symptoms varied with frontal delta and theta activity. CONCLUSIONS: Results indicate that activity in low-frequency bands in schizophrenic patients exceeds the activity of control subjects in distinct areas, and that this focal clustering of neuromagnetic slow waves may be related to psychopathologic characteristics.


Assuntos
Mapeamento Encefálico , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Ritmo Delta , Feminino , Humanos , Magnetoencefalografia , Masculino , Ritmo Teta
15.
Biol Psychiatry ; 49(8): 694-703, 2001 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11313037

RESUMO

BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.


Assuntos
Córtex Cerebral/fisiopatologia , Potenciais Evocados Auditivos/fisiologia , Lateralidade Funcional/fisiologia , Magnetismo , Esquizofrenia/fisiopatologia , Estimulação Acústica , Adulto , Feminino , Humanos , Masculino , Análise e Desempenho de Tarefas
16.
Neuropsychologia ; 38(13): 1749-59, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11099733

RESUMO

Neuroanatomical and -radiological studies have converged to suggest an atypical organisation in the temporal bank of the left-hemispheric Sylvian fissure for dyslexia. Against the background of this finding, we applied high temporal resolution magnetoencephalography (MEG) to investigate functional aspects of the left-hemispheric auditory cortex in 11 right-handed dyslexic children (aged 8-13 years) and nine matched normal subjects (aged 8-14 years). Event-related field components during a passive oddball paradigm with pure tones and consonant-vowel syllables were evaluated. The first major peak of the auditory evoked response, the M80, showed identical topographical distributions in both groups. In contrast, the generating brain structures of the later M210 component were located more anterior to the earlier response in children with dyslexia only. Control children exhibited the expected activation of more posterior source locations of the component that appeared later in the processing stream. Since the group difference in the relative location of the M210 source seemed to be independent of stimulus category, it is concluded that dyslexics and normally literate children differ as to the organisation of their left-hemispheric auditory cortex.


Assuntos
Córtex Auditivo/anormalidades , Córtex Auditivo/fisiologia , Dislexia/etiologia , Magnetoencefalografia/métodos , Adolescente , Análise de Variância , Criança , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Tempo de Reação
17.
Br J Pharmacol ; 127(5): 1240-6, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10455271

RESUMO

Seven esters of alpha-truxillic acid have been synthesized: bis-3-piperidylpropyl ester and its quaternary bis-N-ethyl derivative, bis-N-diethylaminopropyl ester and its quaternary bis-N-methyl derivative, and bis-4-piperidylbutyl ester and its quaternary bis-N-methyl and bis-N-ethyl derivatives. All esters inhibited the specific binding of muscarinic receptor antagonist [methyl-3H]-N-methylscopolamine ([3H]-NMS) to muscarinic receptors in membranes of CHO cell lines stably expressing the human gene for the M1, M2, M3 or M4 subtype of muscarinic receptors. All esters displayed the highest potency at the M2 and the lowest potency at the M3 receptor subtype. In experiments performed on the M2 muscarinic receptor subtype, the affinity between the receptors and the esters was greatly increased when the concentration of ions was diminished. The highest affinities were found for the tertiary bis-3-piperidylpropyl and bis-4-piperidylbutyl aminoesters (equilibrium dissociation constants of 52 and 179 pM, respectively, in the low ionic strength medium). All investigated esters slowed down the dissociation of [3H]-NMS from the M2 muscarinic receptor subtype. [3H]-NMS dissociation from the M1, M3 and M4 muscarinic receptor subtypes was investigated in experiments with the bis-4-piperidylbutyl aminoester and also found to be decelerated. It is concluded that the esters of alpha-truxillic acid act as M2-selective allosteric modulators of muscarinic receptors and that, by their potency, the tertiary bis-3-piperidylpropyl and bis-4-piperidylbutyl aminoesters surpass the other known allosteric modulators of these receptors.


Assuntos
Ciclobutanos/farmacologia , Antagonistas Muscarínicos/farmacologia , N-Metilescopolamina/metabolismo , Receptores Muscarínicos/efeitos dos fármacos , Regulação Alostérica , Animais , Células CHO , Cricetinae , Humanos , Antagonistas Muscarínicos/metabolismo , Receptores Muscarínicos/classificação , Trítio
18.
Psychopharmacology (Berl) ; 105(4): 573-7, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1771224

RESUMO

Heart rate, blood pressure, and subjective stress ratings were recorded from 36 healthy normotensive students at three points in time: during a drug-free baseline, during a baseline 2 h after ingesting single oral doses of atenolol (75 mg), metoprolol (150 mg), or lactate placebo, and during a subsequently administered mental arithmetic test. Both beta-blockers equally reduced baseline heart rate and heart rate response to arithmetic, but subjective stress rating increases to arithmetic were greater for atenolol than for placebo and metoprolol. These results are contrary to peripheral theories of anxiety regulation. While the hydrophilic atenolol barely penetrates the blood-brain barrier, the lipophilic metoprolol can exert direct CNS effects in addition to its peripheral actions. Central stress-dampening effects of lipophilic beta-blockers may override peripheral baroreceptor-mediated stress-promoting effects.


Assuntos
Atenolol/farmacologia , Processos Mentais/fisiologia , Metoprolol/farmacologia , Estresse Psicológico/fisiopatologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Matemática , Valores de Referência , Análise e Desempenho de Tarefas
19.
Psychopharmacology (Berl) ; 110(3): 337-41, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-7831428

RESUMO

Activation of arterial blood pressure has been shown to influence higher central nervous activity. In animals, induction of sleep-like states and increases of seizure and pain thresholds in response to baroreceptor stimulation have been reported. In certain human groups, mechanical stimulation of the carotid baroreceptors also increases pain thresholds. The present paper examines the hypothesis that smokers show baroreceptor dependent antinociception as compared to non-smokers. It is speculated that one effect which rewards smoking is the nicotine induced phasic blood pressure increase which leads to baroreceptor stimulation and dampens pain perception. One hundred and twenty subjects were investigated using a recently developed mechanical baroreceptor stimulation technique and an electrical pain stimulus. The group of heavy smokers showed the predicted effect: their pain thresholds were enhanced during conditions of increased baroreceptor activity as compared to the control condition. The group of medium, light and non-smokers, however, did not show this effect. Neither blood lipid levels nor diastolic or systolic blood pressure paralleled the group differences on baroreceptor dependent antinociception. In heavy smokers, the nicotine induced phasic blood pressure increases might have baroreceptor dependent pain dampening effects, which might be among the reinforcing qualities of smoking.


Assuntos
Lipídeos/sangue , Nociceptores/fisiologia , Pressorreceptores/fisiologia , Fumar/sangue , Fumar/fisiopatologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , Café , Estimulação Elétrica , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Psicometria
20.
Schizophr Res ; 13(1): 23-34, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7947413

RESUMO

Surface-negative brain potentials indicate increased excitability of the underlying cortical neural networks. Consequently, deviant patterns of event-related potentials in schizophrenic patients reveal an atypical regulation of cortical excitability. Twelve patients with a chronic schizophrenic disorder and 12 matched control subjects were investigated using a probe paradigm: A contingent negative variation (CNV) was evoked in a forewarned reaction time paradigm. Clicks were presented before, during and after elicitation of the CNV. Click-evoked responses allow one to 'probe' the current brain state, particularly neuronal excitability, which is also reflected by the slow potentials. During the measurements, subjects pressed one button in response to the offset of the visual warning stimulus and a different button in response to the acoustic probes, the latter button press being a behavioral indication of the brain's excitability. In the forewarned reaction time task, patients developed a CNV with a frontal maximum, while the CNV in control subjects was predominantly centro-parietal. This atypical topographical pattern of the CNV may indicate a different spatio-temporal regulation of cortical preparatory processes in schizophrenics. Motor responses were accelerated during negative potential shifts in both patients and controls, with responses being slower overall in patients. In patients, probe-evoked potentials revealed a smaller N100, but a larger P300, than in controls. The covariation of these brain waves with slow potentials, however, turned out to be similar for both groups.


Assuntos
Atenção/fisiologia , Variação Contingente Negativa/fisiologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Inibição Neural/fisiologia , Esquizofrenia/diagnóstico , Processamento de Sinais Assistido por Computador
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