Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics

Alcoholism is a major health problem in Western countries, yet relatively little is known about the mechanisms by which chronic alcohol abuse causes the pathologic changes associated with the disease. It is likely that chronic alcoholism affects a number of signaling cascades and transcription factors, which in turn result in distinct gene expression patterns. These patterns are difficult to detect by traditional experiments measuring a few mRNAs at a time, but are well suited to microarray analyses. We used cDNA microarrays to analyze expression of approximately 10 000 genes in the frontal and motor cortices of three groups of chronic alcoholic and matched control cases. A functional hierarchy was devised for classification of brain genes and the resulting groups were compared based on differential expression. Comparison of gene expression patterns in these brain regions revealed a selective reprogramming of gene expression in distinct functional groups. The most pronounced differences were found in myelin-related genes and genes involved in protein trafficking. Significant changes in the expression of known alcohol-responsive genes, and genes involved in calcium, cAMP, and thyroid signaling pathways were also identified. These results suggest that multiple pathways may be important for neuropathology and altered neuronal function observed in alcoholism.

Balancing acts: Respiratory sensations, motor control and human posture

1. The present brief review covers some novel aspects of integration between respiration and movement of the body. 2. There are potent viscerosomatic reflexes in animals involving small-diameter pulmonary afferents that, when excited, would limit exercise. However, recent studies using lobeline injections to excite pulmonary afferents in awake humans suggest that there is no evoked reflex motoneuronal inhibition. Instead, the noxious respiratory sensations generated by the vagal afferents may be crucial in the decision to stop exercise. 3. While respiratory movements may affect limb movements, the control of the trunk and limbs can involve interaction (and even interference) with key respiratory muscles, such as the diaphragm. Recent studies have revealed that not only does the diaphragm receive feed-forward drive prior to some limb movements, but that it also contracts both phasically and tonically during repetitive limb movements. 4. Thus, challenges to posture can indirectly challenge ventilation, while coordinated diaphragm contraction may contribute to control of the trunk.

Development of motor system dysfunction following whiplash injury

Dysfunction in the motor system is a feature of persistent whiplash associated disorders. Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms. This study measured prospectively, motor system function (cervical range of movement (ROM), joint position error (JPE) and activity of the superficial neck flexors (EMG) during a test of cranio-cervical flexion) as well as a measure of fear of re-injury (TAMPA) in 66 whiplash subjects within 1 month of injury and then 2 and 3 months post injury. Subjects were classified at 3 months post injury using scores on the neck disability index: recovered (30). Motor system function was also measured in 20 control subjects. All whiplash groups demonstrated decreased ROM and increased EMG (compared to controls) at 1 month post injury. This deficit persisted in the group with moderate/severe symptoms but returned to within normal limits in those who had recovered or reported persistent mild pain at 3 months. Increased EMG persisted for 3 months in all whiplash groups. Only the moderate/severe group showed greater JPE, within 1 month of injury, which remained unchanged at 3 months. TAMPA scores of the moderate/severe group were higher than those of the other two groups. The differences in TAMPA did not impact on ROM, EMG or JPE. This study identifies, for the first time, deficits in the motor system, as early as 1 month post whiplash injury, that persisted not only in those reporting moderate/severe symptoms at 3 months but also in subjects who recovered and those with persistent mild symptoms. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Motor and functional skills of children with developmental coordination disorder: A pilot investigation of measurement issues

This paper reports on the motor and functional outcomes of 20 children with developmental coordination disorder (DCD) aged 4-8 years consecutively referred to a pediatric physiotherapy service. Children with a Movement ABC (M-ABC) score less than the 15th percentile, and with no concurrent medical, sensory, physical, intellectual or neurological impairments, were recruited. The Motor Assessment Outcomes Model (MAOM) [Coster and Haley, Infants and Young Children 4 (1992) 11] provided the theoretical base for measurement selection, and preliminary findings at the activities and participation levels of the model are reported in this article. Children with DCD performed at the lower end of the normal range on the Pea-body Developmental Motor Scales (fine motor total score) (M = 85.65, SD = 12.23). Performance on the Visual Motor Integration Test (VMI) standard scores was within the average range (M = 96.15, SD = 10.69). Videotaped observations of the children's writing and cutting indicated that 29% were left-handed and that a large proportion of all children (31%) utilized unusual pencil grasp patterns and immature prehension of scissors. Measurement at the participation level involved use of the Pictorial Scale of Perceived Competence and Social Acceptance (PCSA) and Pediatric Evaluation of Disability Inventory (PEDI). Overall, these young children rated themselves towards the more competent and accepted end of the PCSA over the dimensions of physical and cognitive competence and peer and maternal acceptance. The PEDI revealed generally average performance on social (M = 49.98, SD = 16.62) and mobility function (M = 54.71, SD = 3.99), however, self-care function was below the average range for age (M = 38.01, SD = 12.19). The utility of the MAOM as a framework for comprehensive measurement of functional and motor outcomes of DCD in young children is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Adult onset Krabbe disease may mimic motor neurone disease

Krabbe's disease (galactocerebrosidase deficiency) rarely presents in adults, usually with predominantly upper motor neurone clinical features. We report a case in whom the clinical features were similar to motor neurone disease. Nerve conduction studies and neuroimaging were important in leading to the correct diagnosis. Differences in adult-onset presentations are described. (C) 2003 Elsevier Science Ltd. All rights reserved.

Effect of changing data collection parameters on statistical motor unit number estimates

The effect of number of samples and selection of data for analysis on the calculation of surface motor unit potential (SMUP) size in the statistical method of motor unit number estimates (MUNE) was determined in 10 normal subjects and 10 with amyotrophic lateral sclerosis (ALS). We recorded 500 sequential compound muscle action potentials (CMAPs) at three different stable stimulus intensities (10–50% of maximal CMAP). Estimated mean SMUP sizes were calculated using Poisson statistical assumptions from the variance of 500 sequential CMAP obtained at each stimulus intensity. The results with the 500 data points were compared with smaller subsets from the same data set. The results using a range of 50–80% of the 500 data points were compared with the full 500. The effect of restricting analysis to data between 5–20% of the CMAP and to standard deviation limits was also assessed. No differences in mean SMUP size were found with stimulus intensity or use of different ranges of data. Consistency was improved with a greater sample number. Data within 5% of CMAP size gave both increased consistency and reduced mean SMUP size in many subjects, but excluded valid responses present at that stimulus intensity. These changes were more prominent in ALS patients in whom the presence of isolated SMUP responses was a striking difference from normal subjects. Noise, spurious data, and large SMUP limited the Poisson assumptions. When these factors are considered, consistent statistical MUNE can be calculated from a continuous sequence of data points. A 2 to 2.5 SD or 10% window are reasonable methods of limiting data for analysis. Muscle Nerve 27: 320–331, 2003

Parvalbumin-, calbindin-, and calretinin-immunoreactive neurons in the prefrontal cortex of the owl monkey (Aotus trivirgatus): A standardized quantitative comparison with sensory and motor areas

Recent studies have revealed regional variation in the density and distribution of inhibitory neurons in different cortical areas, which are thought to reflect area-specific specializations in cortical circuitry. However, there are as yet few standardized quantitative data regarding how the inhibitory circuitry in prefrontal cortex (PFC), which is thought to be involved in executive functions such as cognition, emotion and decision making, compares to that in other cortical areas. Here we used immunohistochemical techniques to determine the density and distribution of parvalbumin (PV)-, calbindin (CB)-, and calretinin (CR)-immunoreactive (ir) neurons and axon terminals in the dorsolateral and orbital PFC of the owl monkey (Aotus trivirgatus), and compared them directly with data obtained using the same techniques in 11 different visual, somatosensory and motor areas. We found marked differences in the density of PV-ir, CB-ir, and CR-ir interneurons in several cortical areas. One hundred and twenty eight of all 234 possible between-area pairwise comparisons were significantly different. The density of specific subpopulations of these cells also varied among cortical areas, as did the density of axon terminals. Comparison of PFC with other cortical areas revealed that 40 of all 66 possible statistical comparisons of the density of PV-ir, CB-ir, and CR-ir cells were significantly different. We also found evidence for heterogeneity in the pattern of labeling of PV-ir, CB-ir, and CR-ir cells and axon terminals between the dorsolateral and orbital subdivisions of PFC. These data are likely to reflect basic differences in interneuron circuitry, which are likely to influence inhibitory function in the cortex. Copyright (C) 2003 S. Karger AG, Basel.

Efeito da mitomicina C em cultura de estroma de pólipos nasais eosinofílicos: indução de apoptose em eosinófilos

A polipose nasossinusal eosinofílica é uma afecção comum a várias doenças, determina acometimento extenso dos seios paranasais e possui grande tendência à recidiva após tratamento. Os eosinófilos exercem papel essencial na patogênese, relacionada a baixo índice de apoptose e a longa permanência destas células ativas nos tecidos. OBJETIVO: Este estudo teve por objetivo avaliar o efeito da mitomicina C na indução de apoptose em eosinófilos presentes no estroma de pólipos nasais eosinofílicos. FORMA DE ESTUDO: Caso controle. MATERIAL E MÉTODO: O estudo foi auto-pareado, com 9 amostras cultivadas em meio RPMI 1640 e avaliadas em zero, 12 e 24 horas. O grupo estudo recebeu mitomicina C numa concentração de 400µg/ml durante 5 minutos. Em cada tempo as duas culturas, controle e estudo, foram submetidas a estudo histopatológico para determinação do índice apoptótico. Utilizou-se a coloração hematoxilina-eosina com aumento microscópico de 1000x. RESULTADO: Pela análise de 674 campos digitalizados observou-se que as culturas tratadas com mitomicina C apresentaram índice apoptótico em 12 horas significativamente maior em relação ao grupo controle (p< 0,001). CONCLUSÃO: Concluiu-se que a mitomicina C é eficaz na indução de apoptose em eosinófilos presentes em estroma de pólipos nasais eosinofílicos.

Emissões otoacústicas por produtos de distorção em ovinos normais e após indução de hiperinsulinemia

As emissões otoacústicas transientes evocadas e as emissões otoacústicas por produtos de distorção vêm assumindo importância significativa na identificação de alterações cocleares. OBJETIVO: Através da monitorização das emissões otoacústicas, registrar os limiares dos produtos de distorção em condições normais e na presença de modificações eletrofisiológicas nas células ciliadas externas cocleares de ovelhas após a indução de hiperinsulinemia aguda. MATERIAL E MÉTODO: Estudo experimental com sete ovelhas no grupo-controle e sete no grupo-estudo. Os níveis de insulina e glicose foram verificados simultaneamente ao registro das emissões otoacústicas por produtos de distorção de 10 em 10 minutos, até o tempo de 90 minutos. O grupo-controle recebeu soro fisiológico, e o grupo-estudo, injeção em bolo de 0,1 U/kg de insulina humana regular. RESULTADOS: Houve diminuição significante nos limiares dos produtos de distorção no grupo-estudo em relação ao grupo-controle nas freqüências acima de 1.500 Hz e após o tempo de 60 minutos (P < 0,001). CONCLUSÃO: O estudo permitiu estabelecer os limiares das emissões otoacústicas por produtos de distorção em ovelhas com constante reprodutibilidade, o que mostra que o método é adequado para uso em investigações audiológicas e otológicas. Ficou, ainda, plenamente identificado que o hiperinsulinismo agudo foi capaz de provocar relevantes modificações nestes limiares.

Participação do nitrogênio na indução de injúrias foliares e na eficácia do herbicida glyphosate

Com o objetivo de avaliar diferentes aspectos da participação do nitrogênio na indução de injúrias foliares e na eficácia do herbicida glyphosate, foram desenvolvidos três experimentos, sendo dois em casa de vegetação, com as espécies Avena strigosa e Ipomoea triloba + Sorghum halepense, e um em campo, com Brachiaria decumbens. Avaliou-se a aplicação de glyphosate combinado com ureia (U), com sulfato de amônio (SA) e com U+AS, além de fertilização prévia do solo com nitrogênio e pulverização de caldas concentradas com até 20% de N. A pulverização de caldas concentradas com até 20% de N não dessecou adequadamente as espécies A. strigosa e B. decumbens, provocando danos máximos de cerca de 30%. A utilização de solução de SA ou de U+SA como veículo de pulverização do glyphosate elevou o controle de I. triloba. As soluções nitrogenadas aceleraram a atividade do glyphosate para dessecação de S. halepense, porém, sem diferenças visíveis aos 28 dias após aplicação. A escolha da dose adequada de glyphosate (1.800 g ha-1) para dessecação de B. decumbens foi fundamental para obtenção de elevado controle, sendo que a única alternativa que elevou a eficácia da menor dose do produto foi a fertilização prévia do solo com 150 kg ha-1 de SA.

Indução de embriões somáticos a partir de embriões zigóticos de Heliconia bihai (L.) L. cv. Lobster Claw Two

As flores tropicais têm contribuído para o aumento do mercado florístico no Brasil; dentre elas destacam-se as do gênero Heliconia. A propagação de helicônias que atinge maior número de mudas ocorre por via vegetativa, por meio da divisão de rizomas, aumentando a probabilidade de disseminação de doenças, podendo, num futuro próximo, comprometer a produção de flores. O cultivo in vitro surge como importante alternativa para proporcionar a produção de mudas de helicônia com elevado padrão de qualidade. Entretanto, a micropropagação de helicônias via ápices caulinares depara-se com problemas de contaminação endofítica, dificultando a multiplicação do explante. Diante disso, fez-se necessário avaliar alternativas que promovam a produção de mudas in vitro, por meio da utilização de outros explantes. Para tanto, realizou-se um experimento, utilizando embriões zigóticos, provenientes de frutos imaturos e maduros de H. bihai (L.) L. cv. Lobster Claw Two, em combinações de AIA (0; 5,70 e 11,41 µm L-1) e 2,4-D (0; 22,62; 45,24; 67,86 e 90,48 µm L-1), para induzir a formação de embriões somáticos durante 90 dias. Por meio de análise histológica, observou-se a formação de embriões somáticos apenas nos embriões zigóticos, provenientes de frutos maduros, cultivados na ausência de reguladores de crescimento.

Indução, análises morfológicas e ultraestruturais de calos de maracujazeiro nativo

A análise de calos que apresentem características embriogênicas é importante para posterior regeneração, in vitro, de espécies com características agronômicas desejáveis, como o maracujazeiro nativo Passiflora gibertii. Diante do exposto, objetivou-se, com este trabalho, analisar a indução de calos oriundos de explantes foliares de Passiflora gibertiiN. E. Brown, bem como caracterizá-los, morfológica e ultraestruturalmente. Para obtenção de calos, folhas cotiledonares foram inoculadas, em meio de cultura, suplementado com picloram e 2,4-D, combinados com cinetina. Após 30 dias em meio de cultura, no escuro, os calos obtidos foram preparados para a visualização em microscopia eletrônica (transmissão e varredura) e microscopia de luz. Os resultados permitem afirmar que a adição de picloram e cinetina ao meio de cultura promove maior formação de calos em explantes foliares de P. gibertii que 2,4-D e cinetina. O regulador 2,4-D proporciona a obtenção de calos com células de formato isodiamétrico, pequenas e com pequeno espaço intercelular, sistema celular organizado e predominância de mitocôndrias de formato arredondado. Já com a utilização do regulador de crescimento picloram, observa-se a predominância de células grandes e de formato alongado, de espaços intercelulares, de sistema celular desorganizado e de mitocôndrias de formato alongado.