RESUMO
The accumulation and aggregation of α-synuclein is a pathognomonic sign of Parkinson's disease (PD). Maneb (MB) exposure has also been reported as one environmental triggering factor of this multifactorial neurodegenerative disease. In our laboratory, we have previously reported that mild overexpression of α-synuclein (200% increase with respect to endogenous neuronal levels) can confer neuroprotection against several insults. Here, we tested the hypothesis that α-synuclein can modulate the neuronal response against MB-induced neurotoxicity. When exposed to MB, cells with endogenous α-synuclein expression displayed increased reactive oxygen species (ROS) associated with diminished glutamate-cysteine ligase catalytic subunit (GCLc) and hemeoxygenase-1 (HO-1) mRNA expressions and upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2) repressor, BTB domain and CNC homolog 1 (BACH1). We found that α-synuclein overexpression (wt α-syn cells) attenuated MB-induced neuronal damage by reducing oxidative stress. Decreased ROS found in MB-treated wt α-syn cells was associated with unaltered GCLc and HO-1 mRNA expressions and decreased BACH1 expression. In addition, the increased SOD2 expression and catalase activity were associated with forkhead box O 3a (FOXO3a) nuclear compartmentalization. Cytoprotective effects observed in wt α-syn cells were also associated with the upregulation of silent information regulator 1 (SIRT1). In control cells, MB-treatment downregulated glutathione peroxidase 4 mRNA levels, which was coincident with increased ROS content, lipid peroxidation, and mitochondrial alterations. These deleterious effects were prevented by ferrostatin-1, an inhibitor of ferroptosis, under conditions of endogenous α-synuclein expression. The overexpression of α-synuclein attenuated MB toxicity by the activation of the same mechanisms as ferrostatin-1. Overall, our findings suggest that mild overexpression of α-synuclein attenuates MB-induced neurotoxicity through the modulation of NRF2 and FOXO3a transcription factors and prevents cell death probably by intervening in mechanisms associated with ferroptosis. Thus, we postulate that early stages of α-synuclein overexpression could be potentially neuroprotective against MB neurotoxicity.
Assuntos
Maneb , Doenças Neurodegenerativas , Síndromes Neurotóxicas , Humanos , alfa-Sinucleína/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , OxirreduçãoRESUMO
OBJECTIVE: The role of high-resolution computed tomography scans in otosclerosis remains uncertain. There is a debate over the relationship between radiological and audiometric findings among patients. METHOD: Pre-operative audiometry and high-resolution computed tomography findings from 40 ears with surgically confirmed otosclerosis were compared. High-resolution computed tomography scan data regarding the characteristics of the disease foci, the endosteal extension and the occurrence of internal auditory canal diverticula were obtained. The influence of each radiological variable on the simple pure tone average, the high-frequency pure tone average and the bone-conduction pure tone average were investigated. RESULTS: Cases with endosteal extension (p = 0.047) and a higher number of affected sites within the otic capsule had a worse bone-conduction pure tone average, although it was only significant for the latter (p = 0.006). Those without concomitant retrofenestral disease (p = 0.019) had better simple pure tone average. CONCLUSION: The number of sites of involvement and concomitant retrofenestral disease seem to significantly impact audiometric findings in otosclerosis.
Assuntos
Orelha Interna , Otosclerose , Humanos , Otosclerose/complicações , Otosclerose/diagnóstico por imagem , Otosclerose/epidemiologia , Audiometria de Tons Puros/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Endothelial dysfunction is a characteristic of systemic arterial hypertension (SAH) and an early marker of atherosclerosis. Aerobic exercise training (AT) improves endothelial function. However, the effects of resistance training (RT) and combined training (CT) on endothelial function remain controversial in individuals with SAH. We determined the effects of AT, RT, and CT on endothelial function and systolic (SBP)/diastolic blood pressure (DBP) in individuals with prehypertension or hypertension. Forty-two participants (54 ± 11 y, resting SBP/DBP 137 ± 9/86 ± 6 mmHg) were randomly allocated into AT (n = 14, 40 min of cycling, 50-75% heart rate reserve), RT (n = 14, 6 resistance exercises, 4 × 12 repetitions, 60% maximum strength) and CT (n = 14, 2 × 12 repetitions of RT + 20 min of AT). All participants performed a 40-minute exercise session twice a week for 8 weeks. Endothelial function was evaluated by brachial artery flow-mediated dilation (FMD). Blood pressure was evaluated through ambulatory monitoring for 24 hours. After 8 weeks of exercise training, blood pressure was reduced in all 3 groups: -5.1 mmHg in SBP (95%CI -10.1, 0.0; p = 0.003) in AT; -4.0 mmHg in SBP (95%CI -7.8, -0.5; p = 0.027) in RT; and -3.2 mmHg in DBP (95%CI -7.9, 1.5; p = 0.001) in CT. All 3 exercise training modalities produced similar improvements in FMD: + 3.2% (95%CI 1.7, 4.6) (p < 0.001) in AT; + 4.0% (95%CI 2.1, 5.7) (p < 0.001) in RT; and +6.8% (95%CI 2.6, 11.1) (p = 0.006) in CT. In conclusion, different exercise training modalities were similarly effective in improving endothelial function but impacts on ambulatory blood pressure appear to be variable in individuals with prehypertension or hypertension.
Assuntos
Pressão Sanguínea , Endotélio Vascular/patologia , Exercício Físico , Hipertensão/patologia , Hipertensão/fisiopatologia , Pré-Hipertensão/patologia , Pré-Hipertensão/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Treinamento ResistidoRESUMO
Industry 4.0 is a synonym for the confluence of technologies that allows the integration of information technology, data science, and automated equipment, to produce smart industrial systems. The process of inserting new technologies into current conventional environments involves a wide range of disciplines and approaches. This article presents the process that was followed to identify and upgrade one station in an industrial workshop to make it compatible with the more extensive system as it evolves into the Industry 4.0 environment. An information processing kit was developed to upgrade the equipment from an automated machine to an Industry 4.0 station. The kit includes a structure to support the sensor and the data processing unit; this unit consisted of a minicomputer that records the data, graded the performance of the components, and sent the data to the cloud for storage, reporting, and further analysis. The information processing kit allowed the monitoring of the inspection system and improved the quality and speed of the inspection process.
RESUMO
Cryptococcosis, caused by Cryptococcus gattii sensu lato, is an emerging disease that was initially found in (sub)tropical regions but recently expanded to temperate regions. Cryptococcus gattii s.l. infections are mostly encountered in healthy individuals, frequently affecting both lungs and the central nervous system (CNS). Usually, C. gattii s.l. is less susceptible to antifungal compounds than its counterpart, C. neoformans s.l. We studied 18 clinical C. gattii s.l. isolates with amplified fragment length polymorphism (AFLP) fingerprinting, mating-typing, multi-locus sequence typing (MLST) and antifungal susceptibility testing. All isolates were C. deuterogattii (genotype AFLP6/VGII), 14 were mating-type α and four were type a. Amphotericin B, itraconazole, voriconazole, posaconazole and isavuconazole showed high activity, with minimum inhibitory concentration (MIC) ranges of 0.063-0.25, 0.031-0.25, 0.031-0.25, 0.031-0.25 and <0.016-0.25 µg mL-1, respectively. Fluconazole and flucytosine had high geometric mean MICs of 2.07 and 3.7 µg mL-1, respectively. Most cases occurred in immunocompetent patients (n = 10; 55.6 %) and CNS involvement was the most common clinical presentation (n = 14; 77.8 %). Three patients (16.7 %) showed sequelae, hyperreflexia, dysarthria, diadochokinesia, anosmia and upper limb weakness. In conclusion, all infections were caused by C. deuterogattii (AFLP6/VGII) and the majority of patients were immunocompetent, with the CNS as the most affected site. All antifungal drugs had high in vitro activity against C. deuterogattii isolates, except fluconazole and flucytosine.
Assuntos
Antifúngicos/farmacologia , Criptococose/microbiologia , Cryptococcus gattii/classificação , Cryptococcus gattii/efeitos dos fármacos , Farmacorresistência Fúngica , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Brasil/epidemiologia , Criptococose/epidemiologia , Cryptococcus gattii/genética , Cryptococcus gattii/isolamento & purificação , Impressões Digitais de DNA , Feminino , Genes Fúngicos Tipo Acasalamento , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências MultilocusRESUMO
Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We have previously demonstrated that iron-overloaded retinas are a good in vitro model for the study of retinal degeneration during iron-induced oxidative stress. In this model we have previously characterized the role of cytosolic phospholipase A2 (cPLA2) and calcium-independent isoform (iPLA2). The aim of the present study was to analyze the implications of Group V secretory PLA2 (sPLA2), another member of PLA2 family, in cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-κB) regulation. We found that sPLA2 is localized in cytosolic fraction in an iron concentration-dependent manner. By immunoprecipitation (IP) assays we also demonstrated an increased association between Group V sPLA2 and COX-2 in retinas exposed to iron overload. However, COX-2 activity in IP assays was observed to decrease in spite of the increased protein levels observed. p65 (RelA) NF-κB levels were increased in nuclear fractions from retinas exposed to iron. In the presence of ATK (cPLA2 inhibitor) and YM 26734 (sPLA2 inhibitor), the nuclear localization of both p65 and p50 NF-κB subunits was restored to control levels in retinas exposed to iron-induced oxidative stress. Membrane repair mechanisms were also analyzed by studying the participation of acyltransferases in phospholipid remodeling during retinal oxidation stress. Acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS), were observed to show an inhibited acylation profile in retinas exposed to iron while phosphatidylethanolamine (PE) showed the opposite. The use of PLA2 inhibitors demonstrated that PS is actively deacylated during iron-induced oxidative stress. Results from the present study suggest that Group V sPLA2 has multiple intracellular targets during iron-induced retinal degeneration and that the specific role of sPLA2 could be related to inflammatory responses by its participation in NF-κB and COX-2 regulation.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Fosfolipases A2 do Grupo V/fisiologia , Degeneração Macular/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Retina/efeitos dos fármacos , Acetilação , Acetiltransferases/metabolismo , Animais , Western Blotting , Bovinos , Citosol/metabolismo , Eletroforese em Gel de Poliacrilamida , Inibidores Enzimáticos/farmacologia , Compostos Ferrosos/toxicidade , Fosfolipases A2 do Grupo V/antagonistas & inibidores , Sobrecarga de Ferro/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilinositóis/metabolismo , Fosfatidilserinas/metabolismo , Fosfolipases A/metabolismo , Fosfolipases A/fisiologia , Retina/metabolismoRESUMO
Both elevated iron concentrations and the resulting oxidative stress condition are common signs in retinas of patients with age-related macular degeneration (AMD). The role of phospholipase A(2) (PLA(2)) during iron-induced retinal toxicity was investigated. To this end, isolated retinas were exposed to increasing Fe(2+) concentrations (25, 200 or 800 µM) or to the vehicle, and lipid peroxidation levels, mitochondrial function, and the activities of cytosolic PLA(2) (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)) were studied. Incubation with Fe(2+) led to a time- and concentration-dependent increase in retinal lipid peroxidation levels whereas retinal cell viability was only affected after 60 min of oxidative injury. A differential release of arachidonic acid (AA) and palmitic acid (PAL) catalyzed by cPLA(2) and iPLA(2) activities, respectively, was also observed in microsomal and cytosolic fractions obtained from retinas incubated with iron. AA release diminished as the association of cyclooxygenase-2 increased in microsomes from retinas exposed to iron. Retinal lipid peroxidation and cell viability were also analyzed in the presence of cPLA(2) inhibitor, arachidonoyl trifluoromethyl ketone (ATK), and in the presence of iPLA(2) inhibitor, bromoenol lactone (BEL). ATK decreased lipid peroxidation levels and also ERK1/2 activation without affecting cell viability. BEL showed the opposite effect on lipid peroxidation. Our results demonstrate that iPLA(2) and cPLA(2) are differentially regulated and that they selectively participate in retinal signaling in an experimental model resembling AMD.
Assuntos
Compostos Ferrosos/toxicidade , Degeneração Macular/induzido quimicamente , Degeneração Macular/enzimologia , Fosfolipases A2/metabolismo , Retina/enzimologia , Animais , Bovinos , Isoenzimas/metabolismo , Isoenzimas/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Técnicas de Cultura de Órgãos , Fosfolipases A2/fisiologiaRESUMO
Ovary development and maturation of Nezara viridula (L.) were evaluated by examining ovariole morphology and the alterations in the biochemical (protein synthesis related to reproduction) composition of the hemolymph. Quantitative and qualitative protein analyses were performed and ovary structural alterations for the pre-reproductive and reproductive stages were recorded. Total concentration of proteins in female hemolymph gradually increased until the end of the pre-mating stage, remaining unaltered thereafter. Proteins linked to reproduction (vitellogenins) appeared in the hemolymph 10 days after adult emergence and indicated the end of the pre-mating stage. After mating, total protein concentration in the hemolymph was lower compared to virgin females; vitellogenin levels were similar during most of the observation period. Oocyte development and maturation were gradual and age dependent. Ten-day-old females had chorionated oocytes ready for fertilization. Mating did not stimulate oocyte development in N. viridula, but the lack of mating activity appeared to have stimulated oocyte resorption in 17-day-old females.
Assuntos
Hemípteros/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Fatores Etários , Animais , Feminino , Maturidade SexualRESUMO
Ovary development and maturation of Nezara viridula (L.) were evaluated by examining ovariole morphology and the alterations in the biochemical (protein synthesis related to reproduction) composition of the hemolymph. Quantitative and qualitative protein analyses were performed and ovary structural alterations for the pre-reproductive and reproductive stages were recorded. Total concentration of proteins in female hemolymph gradually increased until the end of the pre-mating stage, remaining unaltered thereafter. Proteins linked to reproduction (vitellogenins) appeared in the hemolymph 10 days after adult emergence and indicated the end of the pre-mating stage. After mating, total protein concentration in the hemolymph was lower compared to virgin females; vitellogenin levels were similar during most of the observation period. Oocyte development and maturation were gradual and age dependent. Ten-day-old females had chorionated oocytes ready for fertilization. Mating did not stimulate oocyte development in N. viridula, but the lack of mating activity appeared to have stimulated oocyte resorption in 17-day-old females.
Assuntos
Animais , Feminino , Hemípteros/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Fatores Etários , Maturidade SexualRESUMO
A estratégia de auto-instruções tem vindo a ser reconhecida como uma relevante forma de regulação cognitivo-comportamental no incremento das capacidades atencionais, nomeadamente em sujeitos com Transtorno do Deficit de Atenção com Hiperatividade (TDAH). Neste artigo foi avaliada a atenção seletiva e a atenção sustentada em 2 grupos, ambos formados por pessoas com e sem TDAH, sendo que a um deles foi solicitada a realização de auto-instrução, com o objetivo de verificar se o uso desta estratégia promove as capacidades da atenção. Os resultados demonstraram que os sujeitos que realizam a estratégia de auto-instruções, quer apresentem ou não TDAH, manifestam melhores resultados do que os sujeitos que não a realizaram.(AU)
Self-instruction strategy has been recognized as a relevant strategy in cognitive and behavioural regulation as a way of improving attention skills, namely in subjects with Attention Deficit Hyperactivity Disorder (ADHD). This paper aims at demonstrating the effectiveness of this strategy regarding this disorder in subjects with and without ADHD as a mean of promoting attention skills, particularly selective and sustained attention. The results showed that subjects who performed the verbal self-instruction strategy presented better results in both attention processes assessed, than those who did not do it.(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estratégias de Saúde , Atenção , Instruções Programadas como AssuntoRESUMO
A estratégia de auto-instruções tem vindo a ser reconhecida como uma relevante forma de regulação cognitivo-comportamental no incremento das capacidades atencionais, nomeadamente em sujeitos com Transtorno do Deficit de Atenção com Hiperatividade (TDAH). Neste artigo foi avaliada a atenção seletiva e a atenção sustentada em 2 grupos, ambos formados por pessoas com e sem TDAH, sendo que a um deles foi solicitada a realização de auto-instrução, com o objetivo de verificar se o uso desta estratégia promove as capacidades da atenção. Os resultados demonstraram que os sujeitos que realizam a estratégia de auto-instruções, quer apresentem ou não TDAH, manifestam melhores resultados do que os sujeitos que não a realizaram.
Self-instruction strategy has been recognized as a relevant strategy in cognitive and behavioural regulation as a way of improving attention skills, namely in subjects with Attention Deficit Hyperactivity Disorder (ADHD). This paper aims at demonstrating the effectiveness of this strategy regarding this disorder in subjects with and without ADHD as a mean of promoting attention skills, particularly selective and sustained attention. The results showed that subjects who performed the verbal self-instruction strategy presented better results in both attention processes assessed, than those who did not do it.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Atenção , Estratégias de Saúde , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Instruções Programadas como AssuntoRESUMO
The amyloid beta-peptide (Abeta), which is thought to be the major cause of Alzheimer's disease (AD), is known to be capable of aggregating in different states: soluble monomers and oligomers, and insoluble aggregates. The Abeta aggregation state as well as its toxicity has been related to the interaction between the peptide and transition metals such as iron and copper. However, this relationship, as well as the effects of Abeta on the synaptic endings, is not fully understood. The aggregation states of Abeta in the presence of iron and copper, as well as their effects on synaptic viability and signaling were investigated in this work. During acute incubation treatments (5 min-4 h), Abeta/metal impaired mitochondrial function to the same extent as has been observed with the metal alone. However, in the presence of Abeta/iron (10 and 50 muM), plasma membrane integrity was disrupted to a greater extent than when generated by either iron or Abeta alone, indicating that the membrane constitutes the first target of synaptic injury. Akt activation by Abeta/iron was evident after 5 min of incubation and was higher than that observed in the presence of the metal alone. This activation was barely detected after 4 h of incubation, demonstrating that there is no correlation between the extent of synaptic damage and the activation of this kinase. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation profile was different from that observed for Akt. Accordingly, the presence of Abeta/metal could differentially modulate the activity of these kinases. This work shows evidence of the initial events locally triggered at the synapse by Abeta and transition metals. As synapses have been proposed as the starting point of Abeta/metal-triggered events, the characterization of early mechanisms occurring in models that mimic AD could be important for the search of unexplored therapeutics tools.
Assuntos
Peptídeos beta-Amiloides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cobre/farmacologia , Ferro/farmacologia , Sinaptossomos/efeitos dos fármacos , Elementos de Transição/farmacologia , Peptídeos beta-Amiloides/química , Animais , Membrana Celular/efeitos dos fármacos , Cobre/química , Interações Medicamentosas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ferro/química , L-Lactato Desidrogenase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Elementos de Transição/químicaRESUMO
Detergent-resistant membranes (DRMs) are a class of specialized microdomains that compartmentalize several signal transduction processes. In this work, DRMs were isolated from cerebral cortex synaptic endings (Syn) on the basis of their relative insolubility in cold Triton X-100 (1%). The lipid composition and marker protein content were analyzed in DRMs obtained from adult and aged animals. Both DRM preparations were enriched in Caveolin, Flotillin-1 and c-Src and also presented significantly higher sphingomyelin (SM) and cholesterol content than purified Syn. Total phospholipid-fatty acid composition presented an increase in 16:0 (35%), and a decrease in 20:4n-6 (67%) and 22:6n-3 (68%) content in DRM from adults when compared to entire synaptic endings. A more dramatic decrease was observed in the 20:4n-6 and 22:6n-3 content in DRMs from aged animals (80%) with respect to the results found in adults. The coexistence of phosphatidylcholine-specific-phospholipase C (PC-PLC) and phospholipase D (PLD) in Syn was previously reported. The presence of these signaling pathways was also investigated in DRMs isolated from adult and aged rats. Both PC-PLC and PLD pathways generate the lipid messenger diacylglycerol (DAG) by catalyzing PC hydrolysis. PC-PLC and PLD1 localization were increased in the DRM fraction. The increase in DAG generation (60%) in the presence of ethanol, confirmed that PC-PLC was also activated when compartmentalized in DRMs. Conversely, PLD2 was excluded from the DRM fraction. Our results show an age-related differential fatty acid composition and a selective localization of PC-derived signaling in synaptic DRMs obtained from adult and aged rats.
Assuntos
Detergentes/farmacologia , Fosfatidilcolinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Envelhecimento/metabolismo , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Diglicerídeos/metabolismo , Ácidos Graxos/metabolismo , Membranas/efeitos dos fármacos , Membranas/enzimologia , Ratos , Ratos Wistar , Sinapses/enzimologia , Fosfolipases Tipo C/metabolismoRESUMO
Crotoxin B is a basic phospholipase A(2) found in the venom of several Crotalus durissus ssp. rattlesnakes and is one of the subunits that constitute crotoxin, the main component of the venom of these snakes. This heterodimeric toxin is related to important envenomation effects such as neurological disorders, myotoxicity and renal failure. Although crotoxin was first crystallized in 1938, the first structural data only became available in 2007 (for crotoxin B from C. durissus terrificus) and showed an ambiguous result for the biological assembly, which could be either dimeric or tetrameric. In this work, the crystallization, X-ray diffraction data collection at 2.2 A resolution and molecular-replacement solution of a dimeric complex formed by two crotoxin B isoforms from C. durissus collilineatus venom is presented.
Assuntos
Crotoxina/química , Animais , Venenos de Crotalídeos/química , Crotoxina/isolamento & purificação , Cristalização , Cristalografia por Raios X , Dimerização , Fosfolipases A2/química , Estrutura Quaternária de ProteínaRESUMO
O déficit atencional é o factor primordial da Transtorno do Deficit de Atenção com ou sem Hiperactividade (TDA/H). Neste artigo procura-se comprovar as dificuldades na atenção selectiva dos sujeitos com TDA/H em comparação com os sujeitos sem TDA/H, procurando verificar quais os mecanismos deste processo da atenção que estão mais afectados nos sujeitos com TDA/H. Para isso, avaliou-se a atenção selectiva em sujeitos com e sem TDA/H, numa população de 183 sujeitos, em que 152 não apresentam e 31 apresentam TDA/H. Os resultados gerais comprovam que os sujeitos com TDA/H apresentam piores capacidades de atenção selectiva do que os sujeitos sem TDA/H, nomeadamente ao nível dos acertos, dos erros, da capacidade de concentração e do número de elementos processados.(AU)
The attention deficit is the major factor of Attention Deficit Hyperactivity Disorder (ADHD). This paper aims to demonstrate difficulties in selective attention of subjects with ADHD as compared to subjects without ADHD, attempting to verify which mechanisms of selective attention are more affected in subjects with ADHD. For this purpose, we evaluated selective attention in subjects with and without ADHD (152 without and 31 with ADHD), in a population of 183 subjects. The general results show that the subjects with ADHD present lower selective attention skills than the subjects without ADHD, specifically as far as rightness, errors, concentration and processed elements are concerned.(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , AtençãoRESUMO
O déficit atencional é o factor primordial da Transtorno do Deficit de Atenção com ou sem Hiperactividade (TDA/H). Neste artigo procura-se comprovar as dificuldades na atenção selectiva dos sujeitos com TDA/H em comparação com os sujeitos sem TDA/H, procurando verificar quais os mecanismos deste processo da atenção que estão mais afectados nos sujeitos com TDA/H. Para isso, avaliou-se a atenção selectiva em sujeitos com e sem TDA/H, numa população de 183 sujeitos, em que 152 não apresentam e 31 apresentam TDA/H. Os resultados gerais comprovam que os sujeitos com TDA/H apresentam piores capacidades de atenção selectiva do que os sujeitos sem TDA/H, nomeadamente ao nível dos acertos, dos erros, da capacidade de concentração e do número de elementos processados.
The attention deficit is the major factor of Attention Deficit Hyperactivity Disorder (ADHD). This paper aims to demonstrate difficulties in selective attention of subjects with ADHD as compared to subjects without ADHD, attempting to verify which mechanisms of selective attention are more affected in subjects with ADHD. For this purpose, we evaluated selective attention in subjects with and without ADHD (152 without and 31 with ADHD), in a population of 183 subjects. The general results show that the subjects with ADHD present lower selective attention skills than the subjects without ADHD, specifically as far as rightness, errors, concentration and processed elements are concerned.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/psicologiaRESUMO
Crotoxin B is a basic phospholipase A2 found in the venom of Crotalus durissus terrificus and is one of the subunits that constitute crotoxin. This heterodimeric toxin, which is the main component of C. d. terrificus venom, is completed by an acidic, nontoxic and non-enzymatic component (crotoxin A) and is involved in important envenomation effects, such as neurological disorders, myotoxicity and renal failure. Although crotoxin was first crystallized in 1938, no crystal structure is currently available for crotoxin, crotoxin A or crotoxin B. In this work, the crystallization, X-ray diffraction data collection to 2.28 A resolution and molecular-replacement solution of a novel tetrameric complex formed by two dimers of crotoxin B isoforms (CB1 and CB2) is presented.
Assuntos
Crotalus/metabolismo , Crotoxina/química , Crotoxina/metabolismo , Fosfolipases A2/química , Fosfolipases A2/metabolismo , Venenos de Serpentes/química , Venenos de Serpentes/metabolismo , Animais , Crotalus/genética , Crotoxina/genética , Cristalização , Isoenzimas/química , Isoenzimas/metabolismo , Modelos Moleculares , Fosfolipases A2/genética , Ligação Proteica , Estrutura Quaternária de Proteína , Venenos de Serpentes/genética , Difração de Raios XRESUMO
Age-related changes in insulin action on diacylglycerol (DAG) degradation was studied in rat cerebral cortex synaptosomes. The generation of monoacylglycerol (MAG) and water soluble products (WSP, glycerol plus glycerol-3-phosphate) from DAG was studied in cerebral cortex (CC) synaptosomes from adult (4-month-old) and aged (28-month-old) rats. Additionally, the effect of porcine insulin and tyrosine phosphorylation was evaluated in the same group of animals. In this study we demonstrate that the age-related increase in WSP generation was accompanied by unmodified MAG levels. In the presence of diacylglycerol lipase (DAG lipase) inhibitor, RHC-80267, a lower inhibitory effect on MAG production was observed in CC synaptosomes from aged rats with respect to that in adult membranes. Under these experimental conditions, WSP formation was only diminished in aged membranes. Insulin stimulated MAG and WSP formation at long incubation times (30 min) in adult animals, while it had an inhibitory effect in aged animals. Insulin plus vanadate (as tyrosine-phosphatase inhibitor) inhibited MAG production at short incubation times whereas the same effect was observed in aged animals at long times of incubation. WSP formation was stimulated by insulin plus vanadate both in adult and aged animals at 30 min of incubation. Our results show that insulin differentially modulates MAG and WSP production from exogenous PA in CC synaptosomes from aged rats compared with adult rats.
Assuntos
Envelhecimento , Diglicerídeos/biossíntese , Hidrólise , Insulina/metabolismo , Ácidos Fosfatídicos/metabolismo , Animais , Córtex Cerebral/enzimologia , Diglicerídeos/metabolismo , Lipase Lipoproteica/antagonistas & inibidores , Masculino , Monoglicerídeos/biossíntese , Ratos , Ratos Wistar , Sinaptossomos/enzimologiaRESUMO
Aging is a process that affects different organs, of which the brain is particularly susceptible. PA and DAG are central intermediates in the phosphoglyceride as well as in the neutral lipid biosynthetic pathway, and they have also been implicated in signal transduction. Phospholipase D (PLD) and phosphatidate phosphohydrolase (PAP) are the enzymes that generate PA and DAG. The latter can be transformed into MAG by diacylglycerol lipase (DGL). In the present study, we examine how aging modulates the PLD, PAP, and DGL isoforms in cerebellar subcellular fractions from 4- (adult), 28-, and 33-mon-old (aged) rats. PI-4,5-bisphosphonate (PIP2)-dependent PLD, PAP1, and DGL1 were distributed in different percentages in all cerebellum subcellular fractions. On the other hand, PAP2 and DGL2 activities were observed in all subcellular fractions except in the cytosolic fraction. Aging modified the enzyme distribution pattern. In addition, aging decreased nuclear (45%), mitochondrial-synaptosomal (55%), and cytosolic (71%) PAP1 activity and increased (28%) microsomal PAP1 activity. DGL1 activity was decreased in nuclear (85%) and mitochondrial-synaptosomal (63%) fractions by aging. On the other hand, PIP2-dependent PLD activities were increased in the mitochondrial-synaptosomal fraction. PAP2 and DGL2 were increased in the microsomal fraction by 87 and 114%, respectively, and they were decreased in the nuclear fraction. The changes observed in cerebellum PAP1 and DGL1 activities from aged rats with respect to adult rats could be related to modifications in lipid metabolism. Differential PA metabolization during aging through PIP2-dependent PLD/PAP2/DGL2 activities could be related to alterations in the neural signal transduction mechanisms.