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1.
Magn Reson Med ; 91(3): 1268-1280, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38009927

RESUMO

PURPOSE: The aim of this work is to evaluate a new eight-channel transceiver (TxRx) coaxial dipole array for imaging of the human head at 9.4T developed to improve specific absorption rate (SAR) performance, and provide for a more compact and robust alternative to the state-of-the art dipole arrays. METHODS: First, the geometry of a single coaxial element was optimized to minimize peak SAR and sensitivity to the load variation. Next, a multi-tissue voxel model was used to numerically simulate a TxRx array coil that consisted of eight coaxial dipoles with the optimal configuration. Finally, we compared the developed array to other human head dipole arrays. Results of numerical simulations were verified on a bench and in the scanner including in vivo measurements on a healthy volunteer. RESULTS: The developed eight-element coaxial dipole TxRx array coil showed up to 1.1times higher SAR-efficiency than a similar in geometry folded-end and fractionated dipole array while maintaining whole brain coverage and low sensitivity of the resonance frequency to variation in the head size. CONCLUSION: As a proof of concept, we developed and constructed a prototype of a 9.4T (400 MHz) human head array consisting of eight TxRx coaxial dipoles. The developed array improved SAR-efficiency and provided for a more compact and robust alternative to the folded-end dipole design. To the best of our knowledge, this is the first example of using coaxial dipoles for human head MRI at ultra-high field.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Imagens de Fantasmas , Desenho de Equipamento , Cabeça/diagnóstico por imagem
2.
Bull Entomol Res ; 110(1): 144-154, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31218990

RESUMO

We examined the role of the most important metabolic enzyme families in the detoxification of neurotoxic insecticides on adult males and females from susceptible populations of Cydia pomonella (L.), Grapholita molesta (Busck), and Lobesia botrana (Denis & Schiffermüller). The interaction between the enzyme families - carboxylesterases (EST), glutathione-S-transferases (GST), and polysubstrate monooxygenases (PSMO) - with the insecticides - chlorpyrifos, λ-cyhalothrin, and thiacloprid - was studied. Insect mortality arising from the insecticides, with the application of enzyme inhibitors - S,S,S-tributyl phosphorotrithioate (DEF), diethyl maleate (DEM), and piperonyl butoxide (PBO) - was first determined. The inhibitors' influence on EST, GST, and PSMO activity was quantified. EST and PSMO (the phase-I enzymatic activities) were involved in the insecticide detoxification in the three species for both sexes, highlighting the role of EST, whereas GST (phase-II enzymes) was involved only in G. molesta insecticide detoxification. L. botrana exhibited, in general, the highest level of enzymatic activity, with a significantly higher EST activity compared with the other species. It was the only species with differences in the response between sexes, with higher GST and PSMO activity in females than in males, which can be explained as the lower susceptibility of the females to the tested insecticides. A positive correlation between PSMO activity and the thiacloprid LD50s in the different species-sex groups was observed explaining the species-specific differences in susceptibility to the product reported in a previous study.


Assuntos
Inativação Metabólica , Inseticidas , Mariposas/enzimologia , Animais , Feminino , Masculino
3.
Mol Psychiatry ; 23(3): 509-520, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-27994221

RESUMO

Contrary to acute pain, chronic pain does not serve as a warning signal and must be considered as a disease per se. This pathology presents a sensory and psychological dimension at the origin of affective and cognitive disorders. Being largely refractory to current pharmacotherapies, identification of endogenous systems involved in persistent and chronic pain is crucial. The amygdala is a key brain region linking pain sensation with negative emotions. Here, we show that activation of a specific intrinsic neuromodulatory system within the amygdala associated with type 4 metabotropic glutamate receptors (mGlu4) abolishes sensory and affective symptoms of persistent pain such as hypersensitivity to pain, anxiety- and depression-related behaviors, and fear extinction impairment. Interestingly, neuroanatomical and synaptic analysis of the amygdala circuitry suggests that the effects of mGlu4 activation occur outside the central nucleus via modulation of multisensory thalamic inputs to lateral amygdala principal neurons and dorso-medial intercalated cells. Furthermore, we developed optogluram, a small diffusible photoswitchable positive allosteric modulator of mGlu4. This ligand allows the control of endogenous mGlu4 activity with light. Using this photopharmacological approach, we rapidly and reversibly inhibited behavioral symptoms associated with persistent pain through optical control of optogluram in the amygdala of freely behaving animals. Altogether, our data identify amygdala mGlu4 signaling as a mechanism that bypasses central sensitization processes to dynamically modulate persistent pain symptoms. Our findings help to define novel and more precise therapeutic interventions for chronic pain, and exemplify the potential of optopharmacology to study the dynamic activity of endogenous neuromodulatory mechanisms in vivo.


Assuntos
Tonsila do Cerebelo/metabolismo , Dor Crônica/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Tonsila do Cerebelo/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Medo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurotransmissores/metabolismo , Dor/metabolismo , Receptores de Glutamato Metabotrópico/fisiologia , Transmissão Sináptica/fisiologia , Tálamo/metabolismo
4.
Bull Entomol Res ; 106(1): 54-62, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26497943

RESUMO

The main resistance mechanism of codling moth (Cydia pomonella) in the tree fruit area of Lleida (NE Spain) is multifunction oxidases (MFO). We studied the frequency of MFO-resistant adults captured by different lures, with and without pear ester, and flights in orchards under different crop management systems. The factor year affected codling moth MFO-resistance level, particularly in the untreated orchards, highlighting the great influence of codling moth migration on the spread of resistance in field populations. Chemical treatments and adult flight were also very important but mating disruption technique showed no influence. The second adult flight showed the highest frequency, followed by the first flight and the third flight. In untreated orchards, there were no significant differences in the frequency of MFO-resistant individuals attracted by Combo and BioLure. Red septa lures baited with pear ester (DA) captured sufficient insects only in the first generation of 2010, obtaining a significantly lower proportion of MFO-resistant adults than Combo and BioLure. In the chemically treated orchards, in 2009 BioLure caught a significantly lower proportion of MFO-resistant adults than Combo during the first and third flight, and also than DA during the first flight. No significant differences were found between the lures or flights in 2010. These results cannot support the idea of a higher attractiveness of the pear ester for MFO-resistant adults in the field but do suggest a high influence of the response to the attractant depending on the management of the orchard, particularly with regard to the use of chemical insecticides.


Assuntos
Agricultura/métodos , Ésteres/química , Proteínas de Insetos/metabolismo , Mariposas/efeitos dos fármacos , Mariposas/fisiologia , Oxirredutases/metabolismo , Feromônios/farmacologia , Animais , Feminino , Masculino , Pyrus/química , Estações do Ano , Espanha
5.
Neurobiol Dis ; 80: 42-53, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25986729

RESUMO

Autism spectrum disorders are severe neurodevelopmental disorders, marked by impairments in reciprocal social interaction, delays in early language and communication, and the presence of restrictive, repetitive and stereotyped behaviors. Accumulating evidence suggests that dysfunction of the amygdala may be partially responsible for the impairment of social behavior that is a hallmark feature of ASD. Our studies suggest that a valproic acid (VPA) rat model of ASD exhibits an enlargement of the amygdala as compared to controls rats, similar to that observed in adolescent ASD individuals. Since recent research suggests that altered neuronal development and morphology, as seen in ASD, may result from a common post-transcriptional process that is under tight regulation by microRNAs (miRs), we examined genome-wide transcriptomics expression in the amygdala of rats prenatally exposed to VPA, and detected elevated miR-181c and miR-30d expression levels as well as dysregulated expression of their cognate mRNA targets encoding proteins involved in neuronal system development. Furthermore, selective suppression of miR-181c function attenuates neurite outgrowth and branching, and results in reduced synaptic density in primary amygdalar neurons in vitro. Collectively, these results implicate the small non-coding miR-181c in neuronal morphology, and provide a framework of understanding how dysregulation of a neurodevelopmentally relevant miR in the amygdala may contribute to the pathophysiology of ASD.


Assuntos
Tonsila do Cerebelo/metabolismo , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , MicroRNAs/metabolismo , Tonsila do Cerebelo/patologia , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/patologia , Modelos Animais de Doenças , Neurônios/metabolismo , Neurônios/patologia , Ratos , Comportamento Social , Transcriptoma , Ácido Valproico
6.
Bull Entomol Res ; 105(1): 23-31, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25234707

RESUMO

The response of Grapholita molesta (Busck) males to three-component sex pheromone blends containing a 100% ratio of the major sex pheromone component, (Z)-8-dodecenyl acetate and a 10% ratio of (Z)-8-dodecenol, but with varying ratios of (E)-8-dodecenyl acetate (0.4, 5.4, 10.4, 30.4, and 100.1% E-blends) was tested with populations in eight stone and pome fruit orchards in Europe, Asia, and North and South America. Traps baited with the 5.4% E-blend caught significantly more males than traps with any other blend with all populations. Significantly more males were caught in traps baited with the 10.4% E-blend than in traps with the remaining blends, except with the 0.4% E-blend in Turkey. Significant differences in male moth catches occurred between the other blends with the 0.4>30.4% E-blend, and the 30.4>100.1% E-blend. Male moth catches with the 100.1% E-blend only differed from the hexane control in Chile. No apparent differences were noted to these blends in populations collected from pome or stone fruits. Flight tunnel assays to synthetic blends with a subset of populations were similar to the field results, but the breadth of the most attractive E-blends was wider. Flight tunnel assays also demonstrated a high level of male-female cross-attraction among field-collected populations. Female gland extracts from field-collected populations did not show any significant variation in their three-component blends. The only exceptions in these assays were that long-term laboratory populations were less responsive and attractive, and produced different blend ratios of the two minor components than recently collected field populations.


Assuntos
Comunicação Animal , Mariposas/fisiologia , Atrativos Sexuais/farmacologia , Comportamento Sexual Animal , Animais , Feminino , Cadeia Alimentar , Geografia , Masculino , Malus/fisiologia , Prunus/fisiologia
7.
Pneumologie ; 69(3): 147-64, 2015 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-25750095

RESUMO

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the ERS published new reference values based on 74,187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include appropriate age-dependent mean values and lower limits of normal (LLN). This presentation aims at providing the reader with recommendations dealing with standardization and interpretation of spirometry.


Assuntos
Diagnóstico por Computador/normas , Medicina Ambiental/normas , Medicina do Trabalho/normas , Guias de Prática Clínica como Assunto , Pneumologia/normas , Espirometria/normas , Alemanha
8.
Sleep Breath ; 17(3): 985-91, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23149877

RESUMO

PURPOSE: Type D personality, defined as a combination of social inhibition and negative affectivity, has been associated with poor medication adherence and lower adherence to continuous positive airway pressure in patients with sleep-disordered breathing. Up to this date, the association of patient's personality with adherence with a mandibular advancement device (MAD) has not been studied. The purposes of this study were to examine the association between type D personality and poor adherence to MAD treatment and to examine the impact of type D personality on perceived side effects during this treatment. METHODS: Eighty-two patients out of 113 patients with a known baseline type D scale who have started MAD treatment between June 2006 and December 2009 were included. Information about side effects and adherence were collected via a postal questionnaire. Thirty-three patients were using a monobloc MAD and 49 patients were using a duobloc MAD. RESULTS: Forty-five percent of type D patients discontinued MAD treatment, whereas only 15 % of non-type D patients reported treatment discontinuation. The odds ratio for treatment discontinuation was 6.03 (95 % confidence interval 1.22-29.81; p = 0.027) for type D personality, adjusted for age, gender, MAD type (monobloc or duobloc), and decrease in apnea severity. In continuing MAD users, no significant difference in perceived side effects was reported between the personality types. CONCLUSION: This is the first study to examine the relationship between type D personality and adherence to MAD treatment. Type D patients reported a significantly higher discontinuation rate when compared to patients without type D personality.


Assuntos
Avanço Mandibular/instrumentação , Avanço Mandibular/psicologia , Placas Oclusais , Cooperação do Paciente/psicologia , Apneia Obstrutiva do Sono/psicologia , Apneia Obstrutiva do Sono/terapia , Personalidade Tipo D , Adulto , Bélgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/psicologia , Polissonografia , Fatores de Risco
9.
Acta Neurochir Suppl ; 117: 53-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23652657

RESUMO

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterized by persistent thoughts and repetitive ritualistic behaviours. Despite optimal cognitive-behavioral and pharmacological therapy, approximately 10 % of patients remain treatment-resistant. Deep brain stimulation (DBS) is being investigated as experimental therapy for treatment-refractory OCD. In the current study, we determined the relationship between anatomical location of active electrode contacts and clinical outcome in 16 OCD patients undergoing bilateral nucleus accumbens (NAc) DBS. We found that most patients actually do not receive active stimulation in the NAc but in the more laterally, anteriorly and dorsally located ventral part of the anterior limb of the internal capsule, ventral ALIC (vALIC). Our nine patients receiving bilateral vALIC DBS improved on average 73 % on their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, whereas the six patients with their centers of stimulation located otherwise improved on average only 42 %. We therefore propose bilateral vALIC as a promising new DBS target for patients with treatment-refractory OCD. Future studies employing a direct vALIC targeting approach in larger patient numbers are needed to test whether this proposal holds true.


Assuntos
Estimulação Encefálica Profunda/métodos , Cápsula Interna/patologia , Núcleo Accumbens/fisiologia , Transtorno Obsessivo-Compulsivo/terapia , Adulto , Feminino , Seguimentos , Humanos , Cápsula Interna/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/patologia , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Am J Transplant ; 12(6): 1593-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22420417

RESUMO

In response to the current organ shortage-and in an effort to increase the number of registered donors-the present campaign employed a direct-mail marketing strategy that registered 6908 individuals in the state's First-Person Consent Registry (FPCR). In evaluating the most effective of three mailers, 18-year-old individuals (N = 139,356) were randomly assigned to receive: (a) a letter from the Secretary of State (SoS); (b) a brochure from the SoS or (c) both. As hypothesized, the results revealed that exposure to the SoS letter only resulted in a greater registration rate than exposure to the SoS brochure only. Results also revealed that exposure to both the SoS letter and SoS brochure resulted in a greater registration rate than exposure to the SoS brochure only. No difference in registration rate emerged between exposure to the SoS letter and SoS brochure compared to exposure to the SoS letter only. Our results speak to the effectiveness of utilizing personalized direct-mail marketing strategies to promote organ donation with an emphasis on the practical implications of our findings for organ donation practitioners.


Assuntos
Doadores de Tecidos , Adolescente , Humanos
11.
J Environ Qual ; 51(3): 451-461, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35373848

RESUMO

Quantifying spatial and temporal fluxes of phosphorus (P) within and among agricultural production systems is critical for sustaining agricultural production while minimizing environmental impacts. To better understand P fluxes in agricultural landscapes, P-FLUX, a detailed and harmonized dataset of P inputs, outputs, and budgets, as well as estimated uncertainties for each P flux and budget, was developed. Data were collected from 24 research sites and 61 production systems through the Long-term Agroecosystem Research (LTAR) network and partner organizations spanning 22 U.S. states and 2 Canadian provinces. The objectives of this paper are to (a) present and provide a description of the P-FLUX dataset, (b) provide summary analyses of the agricultural production systems included in the dataset and the variability in P inputs and outputs across systems, and (c) provide details for accessing the dataset, dataset limitations, and an example of future use. P-FLUX includes information on select site characteristics (area, soil series), crop rotation, P inputs (P application rate, source, timing, placement, P in irrigation water, atmospheric deposition), P outputs (crop removal, hydrologic losses), P budgets (agronomic budget, overall budget), uncertainties associated with each flux and budget, and data sources. Phosphorus fluxes and budgets vary across agricultural production systems and are useful resources to improve P use efficiency and develop management strategies to mitigate environmental impacts of agricultural systems. P-FLUX is available for download through the USDA Ag Data Commons (https://doi.org/10.15482/USDA.ADC/1523365).


Assuntos
Agricultura , Fósforo , Canadá , Fósforo/análise , Solo , Estados Unidos , Água
12.
Ann Surg Oncol ; 17(6): 1572-80, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20180031

RESUMO

BACKGROUND: Elderly patients who undergo esophagectomy for cancer often have a high prevalence of coexisting diseases, which may adversely affect their postoperative course. We determined the relationship of advanced age (i.e., > or =70 years) with outcome and evaluated age as a selection criterion for surgery. METHODS: Between January 1991 and January 2007, we performed a curative-intent extended transthoracic esophagectomy in 234 patients with cancer of the esophagus. Patients were divided into two age groups: <70 years (group I; 170 patients) and > or =70 years (group II; 64 patients). RESULTS: Both groups were comparable regarding comorbidity (American Society of Anesthesiologists classification), and tumor and surgical characteristics. The overall in-hospital mortality rate was 6.2% (group I, 5%, vs. group II, 11%, P = 0.09). Advanced age was not a prognostic factor for developing postoperative complications (odds ratio, 1.578; 95% confidence interval, 0.857-2.904; P = 0.143). The overall number of complications was equal with 58% in group I vs. 69% in group II (P = 0.142). Moreover, the occurrence of complications in elderly patients did not influence survival (P = 0.174). Recurrences developed more in patients <70 years (58% vs. 42%, P = 0.028). The overall 5-year survival was 35%, and, when included, postoperative mortality was 33% in both groups (P = 0.676).The presence of comorbidity was an independent prognostic factor for survival (P = 0.002). CONCLUSIONS: Advanced age (> or =70 years) has minor influence on postoperative course, recurrent disease, and survival in patients who underwent an extended esophagectomy. Age alone is not a prognostic indicator for survival. We propose that a radical resection should not be withheld in elderly patients with limited frailty and comorbidity.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Idoso Fragilizado , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
13.
Bioinformatics ; 24(16): 1779-86, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18562268

RESUMO

MOTIVATION: Recent research underlines the importance of finegrained knowledge on protein localization. In particular, subcompartmental localization in the Golgi apparatus is important, for example, for the order of reactions performed in glycosylation pathways or the sorting functions of SNAREs, but is currently poorly understood. RESULTS: We assemble a dataset of type II transmembrane proteins with experimentally determined sub-Golgi localizations and use this information to develop a predictor based on the transmembrane domain of these proteins, making use of a dedicated proteinstructure based kernel in an SVM. Various applications demonstrate the power of our approach. In particular, comparison with a large set of glycan structures illustrates the applicability of our predictions on a 'glycomic' scale and demonstrates a significant correlation between sub-Golgi localization and the ordering of different steps in glycan biosynthesis. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Complexo de Golgi/metabolismo , Modelos Biológicos , Modelos Químicos , Reconhecimento Automatizado de Padrão/métodos , Proteínas SNARE/química , Proteínas SNARE/metabolismo , Análise de Sequência de Proteína/métodos , Sequência de Aminoácidos , Inteligência Artificial , Simulação por Computador , Dados de Sequência Molecular , Relação Estrutura-Atividade
14.
Pneumologie ; 63(10): 578-81, 2009 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-19821216

RESUMO

BACKGROUND AND OBJECTIVE: In perspective of a high prevalence of smokers in our population, we find a high proportion of smoking-related morbidity and mortality. Hospitalisation is basically a favourable situation to start smoking cessation. Aim of the study was to show the effectivity of smoking-cessation-counselling as a smoking cessation interventional tool for hospitalized patients. METHODS: We evaluated 25 consecutive patients, who had accepted an offer for smoking cessation counselling, while being hospitalized in a center of pulmonology. Data concerning smoking habits and morbidity had been collected in the course of a qualified smoking-cessation-counselling. Patients with a FNDT > or = 3 had been offered pharmacological support. The smoking behaviour had been re-collected 6 month after discharge via telephoninterview. Partly there was the opportunity to validate the information via measurement of carboxyhemoglobin. RESULTS: Following the smoking-cessation-counselling 20 out of 25 patients (80 %) had quit smoking. After 6 month 11 patients still had been abstinent, in accordance with a long-term-success-rate of 44 %. Patients who accepted a pharmacological support had a 55 % higher long-term-abstinence-rate. CONCLUSION: Qualified smoking-cessation-counselling concomitantly to hospital treatment is feasible and effective. The results encourage distributing and administering this interventional tool in our health system.


Assuntos
Aconselhamento , Pacientes Internados , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/estatística & dados numéricos , Humanos , Projetos Piloto , Fumar/epidemiologia , Fumar/terapia
15.
Neuroscience ; 155(1): 326-35, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18571866

RESUMO

Startle responses are attenuated by prepulse inhibition (PPI), which is considered to reflect a sensorimotor gating mechanism and is impaired in patients suffering from schizophrenia. A midbrain circuit that mediates PPI in rats has been proposed and behavioral experiments have indicated an important role of acetylcholine and GABA in inhibiting startle. We here test the hypothesis that activation of the midbrain neurons can inhibit startle signaling through a cholinergic mechanism. We have developed a brain slice that comprises startle mediating giant pontine neurons as well as midbrain mesopontine neurons required for PPI. Patch clamp recordings of startle mediating brainstem neurons combined with stimulation of sensory afferents within the startle pathway and activation of mesopontine neurons revealed a delayed inhibition of synaptic transmission 300 ms and 1 s after midbrain activation. The latter was reversed by the muscarinic antagonist scopolamine. Further, there was a shift in the paired pulse ratio 1 s but not 300 ms after midbrain stimulation. Our results show that there is a direct cholinergic projection from the proposed PPI midbrain circuit to startle mediating neurons in the brainstem and that this projection inhibits synaptic transmission in the startle pathway in a distinct time window through the activation of presynaptic muscarinic receptors. Moreover, there is indication for a different receptor that mediates inhibition through this projection in a shorter time window and is located postsynaptically. Our results contribute to the understanding of mechanisms underlying PPI, which is important for developing new targets in the treatment of disorders accompanied with pre-attentive cognitive deficits.


Assuntos
Acetilcolina/metabolismo , Mesencéfalo/citologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Reflexo de Sobressalto/fisiologia , Estimulação Acústica/métodos , Aminoácidos/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Antagonistas Colinérgicos/farmacologia , Estimulação Elétrica/métodos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Técnicas In Vitro , Mecamilamina/farmacologia , Inibição Neural/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp/métodos , Ratos , Ratos Sprague-Dawley , Escopolamina/farmacologia
16.
Mov Disord ; 23(8): 1146-53, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18442104

RESUMO

Thalamic stimulation and thalamotomy for treatment of tremor due to Parkinson's disease, essential tremor, and multiple sclerosis were compared in a randomized trial. The symptomatic and functional outcome was studied after 5 years of follow-up. Sixty-eight patients were treated (45 Parkinson's disease, 13 essential tremor, 10 multiple sclerosis) by thalamotomy (n = 34) or thalamic stimulation (n = 34). After 5 years, 48 patients were available for follow-up. The primary outcome measure was change in functional status measured by the Frenchay Activities Index (FAI), scores ranging from 0 to 60. Secondary outcome measures were tremor severity, frequency of complications, and patients' assessment of the outcome. The mean difference in FAI scores between thalamic stimulation and thalamotomy was 4.4 (95% CI: 1.1-7.7) after 6 months, 3.3 (95% CI: -0.03-6.6) after 2 years and 4.0 (95% CI: 0.3-7.7) after 5 years in favor of stimulation. Tremor suppression was equally effective after both procedures, and stable in Parkinson patients. In ET and multiple sclerosis, a diminished effect of stimulation was observed in half of the patients. There were six stimulation equipment-related complications, but neurological side effects of surgery were higher after thalamotomy. Subjective outcome-assessment by the patients was more favorable in the stimulation group.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial/terapia , Esclerose Múltipla/terapia , Doença de Parkinson/terapia , Tálamo/fisiopatologia , Tálamo/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico
17.
Ann Bot ; 102(3): 331-42, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18621967

RESUMO

BACKGROUND AND AIMS: Alpha-gliadin proteins are important for the industrial quality of bread wheat flour, but they also contain many epitopes that can trigger celiac (coeliac) disease (CD). The B-genome-encoded alpha-gliadin genes, however, contain very few epitopes. Controlling alpha-gliadin gene expression in wheat requires knowledge on the processes of expression and deposition of alpha-gliadin protein during wheat grain development. METHODS: A 592-bp fragment of the promotor of a B-genome-encoded alpha-gliadin gene driving the expression of a GUS reporter gene was transformed into wheat. A large number of transgenic lines were used for data collection. GUS staining was used to determine GUS expression during wheat kernel development, and immunogold labelling and tissue printing followed by staining with an alpha-gliadin-specific antibody was used to detect alpha-gliadin protein deposited in developing wheat kernels. The promoter sequence was screened for regulatory motifs and compared to other available alpha-gliadin promoter sequences. KEY RESULTS: GUS expression was detected primarily in the cells of the starchy endosperm, notably in the subaleurone layer but also in the aleurone layer. The alpha-gliadin promoter was active from 11 days after anthesis (DAA) until maturity, with an expression similar to that of a 326-bp low molecular weight (LMW) subunit gene promoter reported previously. An alpha-gliadin-specific antibody detected alpha-gliadin protein in protein bodies in the starchy endosperm and in the subaleurone layer but, in contrast to the promoter activity, no alpha-gliadin was detected in the aleurone cell layer. Sequence comparison showed differences in regulatory elements between the promoters of alpha-gliadin genes originating from different genomes (A and B) of bread wheat both in the region used here and upstream. CONCLUSIONS: The results suggest that additional regulator elements upstream of the promoter region used may specifically repress expression in the aleurone cell layer. Observed differences in expression regulator motifs between the alpha-gliadin genes on the different genomes (A and B) of bread wheat leads to a better understanding how alpha-gliadin expression can be controlled.


Assuntos
Regulação da Expressão Gênica de Plantas , Gliadina/genética , Plantas Geneticamente Modificadas/genética , Regiões Promotoras Genéticas , Triticum/genética , Epitopos/genética , Epitopos/metabolismo , Genes Reporter , Gliadina/metabolismo , Glucuronidase/genética , Glucuronidase/metabolismo , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Triticum/metabolismo
18.
Acta Neurochir (Wien) ; 150(4): 345-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18278573

RESUMO

BACKGROUND: We studied the use of (201)Thallium SPECT and L-[1-(11)C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with (192)Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan. METHODS: Twenty-one patients underwent (201)Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation. FINDINGS: SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up. CONCLUSION: Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.


Assuntos
Braquiterapia , Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Glioblastoma/radioterapia , Radioisótopos de Irídio/uso terapêutico , Recidiva Local de Neoplasia/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Radioisótopos de Carbono , Terapia Combinada , Diagnóstico Diferencial , Intervalo Livre de Doença , Feminino , Seguimentos , Glioblastoma/diagnóstico por imagem , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Humanos , Radioisótopos de Irídio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Tomografia por Emissão de Pósitrons , Complicações Pós-Operatórias/cirurgia , Lesões por Radiação/diagnóstico por imagem , Radioterapia Adjuvante , Reoperação , Sensibilidade e Especificidade , Radioisótopos de Tálio , Tirosina
19.
Clin Neurol Neurosurg ; 109(7): 607-12, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17555870

RESUMO

The development of brain necrosis is life-long risk of repeat radiation therapy, even after a long time interval and a moderate radiation dose. We report on a 34-year-old patient who had prophylactic cranial irradiation with 25Gy and adjuvant chemotherapy in childhood for leukaemia and in adulthood, 28 years later, therapeutic radiotherapy with 54Gy for an atypical (WHO grade II) meningioma. About 2 years later he developed a contrast-enhancing lesion on MRI-scan that was indicative of a tumor according to a thallium-201 ((201)Tl) SPECT scan. Histopathology of the operated contrast-enhancing lesion showed extensive radionecrosis. Radiation necrosis is a small but serious risk after repeat radiation therapy, even after a very long-term interval, the delivery of small fractions and an average cumulative total dose. Patients undergoing repeat radiotherapy therefore need to be followed life-long for potential late radiation toxicity.


Assuntos
Irradiação Craniana/efeitos adversos , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Neoplasias Primárias Múltiplas/radioterapia , Neoplasias Induzidas por Radiação/radioterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Lesões por Radiação/diagnóstico , Lobo Temporal/efeitos da radiação , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Terapia Combinada , Diagnóstico Diferencial , Seguimentos , Gliose/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Necrose , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Induzidas por Radiação/cirurgia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Radioterapia Adjuvante , Retratamento , Lobo Temporal/patologia , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X
20.
Acta Neurochir Suppl ; 97(Pt 2): 119-25, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17691297

RESUMO

Surgical therapy for movement disorders has been practiced since the early 20th century, mostly for Parkinson's disease. At its onset, large destructive procedures like open resection of cortex, parts of the basal ganglia or its fibre connections produced variable, ill-documented results. With the introduction of the stereotactic operating technique in the second half of the century, ablative surgery became more refined, and more selective interventions became possible to alleviate the suffering of those patients for whom no other treatment modalities were yet available. However, the introduction of levodopa-based pharmacological therapy pushed surgical therapy almost completely to the background. In the past two decades, there has been a resurgence of interest in surgery for movement disorders, due to both limitations of long-term pharmacological therapy and the advent of the treatment modality of deep brain stimulation. The subject has now grown into a large field of clinical and scientific interest. Parkinson's disease is the most widespread surgical indication, but in other movement disorders considerable improvement can be achieved by surgery as well, most notably in dystonia. A short review of the surgical therapy for these disorders is presented.


Assuntos
Transplante de Tecido Encefálico , Estimulação Encefálica Profunda/métodos , Eletrocirurgia/métodos , Transtornos dos Movimentos/cirurgia , Eletrodos , Humanos , Transtornos dos Movimentos/classificação , Transtornos dos Movimentos/patologia
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