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Swietenia macrophylla King is a plant commonly known as Brazilian mahogany. The wood from its stem is highly prized for its exceptional quality, while its leaves are valued for their high content of phragmalin-type limonoids, a subclass of compounds known for their significant biological activities, including antimalarial, antitumor, antiviral, and anti-inflammatory properties. In this context, twelve isolated limonoids from S. macrophylla leaves were employed as standards in mass spectrometry-based molecular networking to unveil new potential mass spectrometry signatures for phragmalin-type limonoids. Consequently, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was utilized for data acquisition. Subsequently, the obtained data were analyzed using the Global Natural Products Social Molecular Networking platform based on spectral similarity. In summary, this study identified 24 new putative phragmalin-type limonoids for the first time in S. macrophylla. These compounds may prove valuable in guiding future drug development efforts, leveraging the already established biological activities associated with limonoids.
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Limoninas , Meliaceae , Limoninas/química , Meliaceae/química , Espectrometria de Massas , Brasil , Estrutura MolecularRESUMO
This article reports the annals of a national consensus meeting on add-ons and social networks in Assisted Reproduction Techniques (ART). The panel of experts has developed a set of consensus points and this document is intended to be referenced as a national consensus to allow social networks and add-ons to be used in ART, following the standards of the Code of Medical Ethics and the Federal Council of Medicine, in a safe ethical and responsible way.
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The anti-obesity thyroid hormone, triiodothyronine (T3), and irisin, an exercise- and/or cold-induced myokine, stimulate thermogenesis and energy consumption while decreasing lipid accumulation. The involvement of ATP signaling in adipocyte cell function and obesity has attracted increasing attention, but the crosstalk between the purinergic signaling cascade and anti-obesity hormones lacks experimental evidence. In this study, we investigated the effects of T3 and irisin in the transcriptomics of membrane-bound purinoceptors, ectonucleotidase enzymes and nucleoside transporters participating in the purinergic signaling in cultured human adipocytes. The RNA-seq analysis revealed that differentiated adipocytes express high amounts of ADORA1, P2RY11, P2RY12, and P2RX6 gene transcripts, along with abundant levels of transcriptional products encoding to purine metabolizing enzymes (ENPP2, ENPP1, NT5E, ADA and ADK) and transporters (SLC29A1, SCL29A2). The transcriptomics of purinergic signaling markers changed in parallel to the upsurge of "browning" adipocyte markers, like UCP1 and P2RX5, after treatment with T3 and irisin. Upregulation of ADORA1, ADORA2A and P2RX4 gene transcription was obtained with irisin, whereas T3 preferentially upregulated NT5E, SLC29A2 and P2RY11 genes. Irisin was more powerful than T3 towards inhibition of the leptin gene transcription, the SCL29A1 gene encoding for the ENT1 transporter, the E-NPP2 (autotaxin) gene, and genes that encode for two ADP-sensitive P2Y receptors, P2RY1 and P2RY12. These findings indicate that anti-obesity irisin and T3 hormones differentially affect the purinergic signaling transcriptomics, which might point towards new directions for the treatment of obesity and related metabolic disorders that are worth to be pursued in future functional studies.
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Fibronectinas , Transcriptoma , Tri-Iodotironina , Humanos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Obesidade/genética , Obesidade/metabolismo , RNA-Seq , Tri-Iodotironina/farmacologia , Tri-Iodotironina/metabolismoRESUMO
Head-mounted displays are virtual reality devices that may be equipped with sensors and cameras to measure a patient's heart rate through facial regions. Heart rate is an essential body signal that can be used to remotely monitor users in a variety of situations. There is currently no study that predicts heart rate using only highlighted facial regions; thus, an adaptation is required for beats per minute predictions. Likewise, there are no datasets containing only the eye and lower face regions, necessitating the development of a simulation mechanism. This work aims to remotely estimate heart rate from facial regions that can be captured by the cameras of a head-mounted display using state-of-the-art EVM-CNN and Meta-rPPG techniques. We developed a region of interest extractor to simulate a dataset from a head-mounted display device using stabilizer and video magnification techniques. Then, we combined support vector machine and FaceMash to determine the regions of interest and adapted photoplethysmography and beats per minute signal predictions to work with the other techniques. We observed an improvement of 188.88% for the EVM and 55.93% for the Meta-rPPG. In addition, both models were able to predict heart rate using only facial regions as input. Moreover, the adapted technique Meta-rPPG outperformed the original work, whereas the EVM adaptation produced comparable results for the photoplethysmography signal.
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Óculos Inteligentes , Realidade Virtual , Humanos , Frequência Cardíaca , Fotopletismografia/métodos , Aprendizado de MáquinaRESUMO
Margaritaria nobilis is a shrubby species widely distributed in Brazil from the Amazon to the Atlantic Rainforest. Its bark and fruit are used in the Peruvian Amazon for disinfecting abscesses and as a tonic in pregnancy, respectively, and its leaves are used to treat cancer symptoms. From analyses via UHPLC-MS/MS, we sought to determine the chemical profile of the ethanolic extract of M. nobilis leaves by means of putative analyses supported by computational tools and spectral libraries. Thus, it was possible to annotate 44 compounds, of which 12 are phenolic acid derivatives, 16 are O-glycosylated flavonoids and 16 hydrolysable tannins. Among the flavonoids, although they are known, except for kaempferol, which has already been isolated from this species, the other flavonoids (10, 14, 15, 21, 24-26, 28-30, 33-35, 40 and 41) are being reported for the first time in the genus. Among the hydrolysable tannins, six ellagitannins present the HHDP group (6, 19, 22, 31, 38 and 43), one presents the DHHDP group (5), and four contain oxidatively modified congeners (12, 20, 37 and 39). Through the annotation of these compounds, we hope to contribute to the improved chemosystematics knowledge of the genus. Furthermore, supported by a metric review of the literature, we observed that many of the compounds reported here are congeners of authentically bioactive compounds. Thus, we believe that this work may help in understanding future pharmacological activities.
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ABSTRACT Evaluate the student's satisfaction in Physical Education (PE) classes can contribute to help teachers in developing strategies to better planning and get students more motivated. The aim of this study is to describe what students' value most and why in a PE class. It was used a qualitative and descriptive approach of the critical incidents in a PE classroom interviewing 278 Portuguese students. The results reveal in the satisfaction striking moments, playing and compete, getting individually and collective success in a satisfactory class climate. The less welcome striking moments were a mixture of playing, compete and failure. The warmup and negative class climate also were reported as not very gratifying. The fun moments reported were personal realization, pleasure and sharing. The teacher appreciation reveals pedagogical interactions, specific knowledge and personal conduct. The students like PE classes. Planning by the PE teacher should maximize opportunities of enjoyable situations by the students, in order to improve their motivation.
RESUMO Avaliar a satisfação do aluno nas aulas de Educação Física (EF) pode contribuir para ajudar os professores no desenvolvimento de estratégias para melhor planear e motivar os alunos. O objetivo deste estudo é descrever o que os alunos valorizam e porquê numa aula de EF. Utilizou-se uma abordagem qualitativa e descritiva dos incidentes críticos numa aula de EF entrevistando 278 alunos portugueses. Os resultados revelam satisfação nos momentos marcantes no jogar e na competição, obtendo sucesso individual e coletivo num clima de classe satisfatório. Os momentos menos bem-vindos foram uma mistura de jogo, competição e fracasso. O aquecimento e um clima de classe negativo também foi relatado como não muito gratificante. Os momentos divertidos relatados foram a realização pessoal, o prazer e o compartilhamento. A valorização do professor revela interações pedagógicas, conhecimentos específicos e conduta pessoal. Os alunos gostam de aulas de EF. O planeamento do professor de EF deve maximizar as oportunidades de situações agradáveis por parte dos alunos a fim de melhorar a motivação deles.
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The main challenge of plant chemical diversity exploration is how to develop tools to study exhaustively plant tissues. Their sustainable sourcing is a limitation as bioguided strategies and dereplication need quite large amounts of plant material. We examine if alternative solutions could overcome these difficulties by obtaining a secure, sustainable, and scalable source of tissues able to biosynthesize an array of metabolites. As this approach would be as independent of the botanical origin as possible, we chose eight plant species from different families. We applied a four steps culture establishment procedure, monitoring targeted compounds through mass spectrometry-based analytical methods. We also characterized the capacities of leaf explants in culture to produce diverse secondary metabolites. In vitro cultures were successfully established for six species with leaf explants still producing a diversity of compounds after the culture establishment procedure. Furthermore, explants from leaves of axenic plantlets were also analyzed. The detection of marker compounds was confirmed after six days in culture for all tested species. Our results show that the first stage of this approach aiming at easing exploration of plant chemodiversity was completed, and leaf tissues could offer an interesting alternative providing a constant source of natural compounds.
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Produtos Biológicos/metabolismo , Folhas de Planta/metabolismo , Plantas/metabolismo , Produtos Biológicos/química , Espectrometria de Massas , Folhas de Planta/química , Plantas/químicaRESUMO
Obesity is a worldwide health problem which have reached pandemic proportions, now also including low and middle-income countries. Excessive or abnormal fat deposition in the abdomen especially in the visceral compartment is tightly associated with a high metabolic risk for arterial hypertension, type II diabetes, cardiovascular diseases, musculoskeletal disorders (especially articular degeneration) and some cancers. Contrariwise, accumulation of fat in the subcutaneous compartment has been associated with a neutral metabolic impact, favoring a lower risk of insulin resistance. Obesity results more often from an avoidable imbalance between food consumption and energy expenditure. There are several recommended strategies for dealing with obesity, including pharmacological therapies, but their success remains incomplete and may not compensate the associated adverse effects. Purinergic signaling operated by ATP and its metabolite, adenosine, has attracted increasing attention in obesity. The extracellular levels of purines often reflect the energy status of a given cell population. Adenine nucleotides and nucleosides fine tuning control adipogenesis and mature adipocytes function via the activation of P2 and P1 purinoceptors, respectively. These features make the purinergic signaling cascade a putative target for therapeutic intervention in obesity and related metabolic syndromes. There are, however, gaps in our knowledge regarding the role of purines in adipocyte precursors differentiation and mature adipocytes functions, as well as their impact among distinct adipose tissue deposits (e.g. white vs. brown, visceral vs. subcutaneous), which warrants further investigations before translation to clinical trials can be made.
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Adipogenia/fisiologia , Obesidade/metabolismo , Purinas/metabolismo , Receptores Purinérgicos P1/metabolismo , Receptores Purinérgicos/metabolismo , Transdução de Sinais/fisiologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Humanos , Obesidade/patologiaRESUMO
BACKGROUND/AIMS: In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A2A and muscarinic M1 receptors in the recovery of neuromuscular tetanic depression caused by the blockage of high-affinity choline transporter (HChT) by hemicholinium-3 (HC-3), a condition that mimics a myasthenia-like condition. METHODS: Rat diaphragm preparations were indirectly stimulated via the phrenic nerve trunk with 50-Hz frequency trains, each consisting of 500-750 supramaximal intensity pulses. The tension at the beginning (A) and at the end (B) of the tetanus was recorded and the ratio (R) B/A calculated. RESULTS: Activation of A2A and M1 receptors with CGS21680 (CGS; 2 nmol/L) and McN-A-343c (McN; 3 µmol/L) increased R values. Similar facilitatory effects were obtained with forskolin (FSK; 3 µmol/L) and phorbol 12-myristate 13-acetate (PMA; 10 µmol/L), which activate adenylate cyclase and protein kinase C respectively. HC-3 (4 µmol/L) decreased transmitter exocytosis measured by real-time videomicroscopy with the FM4-64 fluorescent dye and prevented the facilitation of neuromuscular transmission caused by CGS, McN, and FSK, with a minor effect on PMA. The acetylcholinesterase inhibitor, neostigmine (NEO; 0.5 µmol/L), also decreased transmitter exocytosis. The paradoxical neuromuscular tetanic fade caused by NEO (0.5 µmol/L) was also prevented by HC-3 (4 µmol/L) and might result from the rundown of the positive feedback mechanism operated by neuronal nicotinic receptors (blocked by hexamethonium, 120 µmol/L). CONCLUSION: Data suggest that the recovery of tetanic neuromuscular facilitation by adenosine A2A and M1 receptors is highly dependent on HChT activity and may be weakened in myasthenic patients when HChT is inoperative.
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Proteínas de Membrana Transportadoras/fisiologia , Receptor A2A de Adenosina/fisiologia , Receptor Muscarínico M1/fisiologia , Período Refratário Eletrofisiológico/efeitos dos fármacos , Cloreto de (4-(m-Clorofenilcarbamoiloxi)-2-butinil)trimetilamônio/farmacologia , Adenosina/análogos & derivados , Adenosina/farmacologia , Animais , Colforsina/farmacologia , Diafragma/efeitos dos fármacos , Diafragma/fisiologia , Hemicolínio 3/farmacologia , Neostigmina/farmacologia , Fenetilaminas/farmacologia , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/fisiologia , Ratos , Ratos Wistar , Transmissão Sináptica , Tétano/tratamento farmacológico , Tétano/fisiopatologia , Acetato de Tetradecanoilforbol/farmacologiaAssuntos
Humanos , Feminino , Infertilidade , Inseminação Artificial , Inseminação Artificial/métodosRESUMO
OBJECTIVE: To evaluate the double-stimulation protocol efficacy over conventional ovarian stimulation in recovering a more adequate number of oocytes and increase the number of embryos to be transferred or to be genetically analyzed. METHODS: A retrospective and comparative study with 13 patients who underwent unsuccessful in vitro fertilization (IVF) cycles with a conventional antagonist ovarian stimulation protocol and repeat the attempt with a double stimulation protocol. The following variables were analyzed: number of oocytes collected, mature oocytes collected, fertilization rate, blastocyst rate, biopsied blastocyst rate and euploidy rate. RESULTS: The double stimulation protocol had a significant higher number of oocytes collected (p=0.007) and mature oocytes to be injected (p=0.01). There was no statistically significant difference in fertilization (p=0.78) and blastocyst (p=0.59) rates. CONCLUSION: Double stimulation favors patients who are at risk of incurring several attempts of IVF to achieve pregnancy.
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Blastocisto/fisiologia , Fertilização in vitro/estatística & dados numéricos , Ciclo Menstrual/psicologia , Indução da Ovulação/métodos , Indução da Ovulação/estatística & dados numéricos , Adulto , Feminino , Humanos , Gravidez , Estudos RetrospectivosRESUMO
It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca2+]i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats.
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Potenciação de Longa Duração/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilprednisolona/farmacologia , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Cálcio/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Memória/classificação , Memória/fisiologia , Metilprednisolona/metabolismo , Ratos , Ratos Wistar , Sinapses/fisiologiaRESUMO
BACKGROUND: Leptin and its receptor are present in spermatozoa; however, the role of leptin in sperm function is still controversial. Our present study aimed at demonstrating the effect of cryopreservation on sperm DNA fragmentation (DNAf) and investigating the possible effects of sperm capacitation techniques and leptin in vitro incubation on frozen-thawed sperm DNAf and oxidative stress. METHODS: Samples of 45 normospermic men attending for infertility investigation at Vida Centro de Fertilidade, Rio de Janeiro, Brazil, were frozen and thawed with or without capacitation and leptin incubation prior to freezing. Sperm DNA fragmentation was evaluated by Sperm Chromatin Dispersion Assay before and after cryopreservation and oxidative stress parameters were measured by spectrophotometry with and without leptin incubation. Statistical analysis was performed using paired t test to compare DNAf between groups before and after freeze-thaw cycle, to compare groups before and after capacitation and leptin incubation and oxidative measurements before and after leptin incubation. Statistical significance was considered when p≤0.05. RESULTS: Our results revealed a significant post-thaw rise in sperm DNAf compared with fresh samples (p=0.0003). Sperm DNAf was significantly reduced when sperm capacitation was performed before freezing, when compared to those frozen with no previous capacitation (p=0.01). The addition of leptin to capacitated sperm before freezing reduced DNAf (p<0.0001) and enhanced superoxide dismutase (p=0.001) and glutathione peroxidase (p=0.02) antioxidant enzymes activity. CONCLUSION: The addition of leptin to capacitated sperm can improve sperm DNA quality following cryopreservation, possibly by inducing the activity of certain antioxidant enzymes.
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Resumo O estudo teve como objetivo identificar e descrever as ações de promoção à saúde relacionadas à atividade física de idosos nas unidades básicas de saúde, assim como a percepção dos responsáveis sobre essa prática. Tratou-se de uma pesquisa transversal, de abordagem quantitativa, realizada em Diamantina, Minas Gerais, em 2012. Um instrumento com 28 assertivas, organizado na forma de escala Likert, foi utilizado durante as entrevistas com 28 responsáveis por tais ações. Constataram-se 11 ações educativas de promoção da saúde relacionadas à atividade física para idosos, cinco de responsabilidade dos professores e alunos de uma instituição pública de ensino e seis de responsabilidade dos profissionais das equipes de saúde da família. As ações observadas foram ‘grupo de caminhada e exercícios (alongamentos)’, ‘grupo de coluna’ e ‘Qigong’. Os participantes demonstraram seu entendimento sobre os benefícios das atividades físicas para os idosos, o impacto dessas ações na saúde pública e a necessidade de permanente capacitação.
Abstract The study aimed to identify and describe health promotion actions related to physical activity among elderly people at basic health units and the perception of those responsible for this practice. This was a cross-sectional survey using a quantitative approach carried out in Diamantina, Minas Gerais State, Brazil, in 20112. A 28-questions survey, organized in the form of a Likert scale, was used during the interviews carried out among 28 people in charge of such actions. Eleven educational health promotion actions related to physical activity among elderly people were found, five of which under the responsibility of teachers and students of a public school, while six under headed by professionals from the family health teams. The actions observed were ‘walk and exercise group (stretching),’ ‘back group,’ and ‘Qigong.’ Participants demonstrated their understanding of the benefits afforded by phy-sical activity for the elderly, the impact these actions have on public health, and the need for ongoing training.
Resumen El estudio tuvo como objetivo identificar y describir las acciones de promoción de la salud relacionadas con la actividad física de adultos mayores en las unidades básicas de salud, así como la percepción de los responsables sobre esta práctica. Se trató de una investigación transversal, de abordaje cuantitativo, realizado en Diamantina, estado de Minas Gerais, Brasil, en 2012. Se utilizó un instrumento con veintiocho afirmaciones, organizado en forma de escala Likert, durante las entrevistas con 28 responsables de tales acciones. Se cons-tataron 11 acciones educativas de promoción de la salud relacionadas con la actividad física para adultos mayores, cinco de responsabilidad de los profesores y alumnos de una institución pública de enseñanza y seis de responsabilidad de los profesionales de los equipos de salud de la familia. Las acciones observadas fueron "grupo de caminata y ejercicio (estiramientos)", "grupo de columna" y " Qigong". Los participantes demostraron comprensión sobre los beneficios de las actividades físicas para adultos mayores, el impacto de estas acciones en la salud pública y la necesidad de capacitación permanente.
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Humanos , Envelhecimento , Exercício Físico , Saúde da Família , Educação em Saúde , Educação Continuada , Atividade MotoraRESUMO
Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 µg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.
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Antioxidantes/farmacologia , Meliaceae/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Sobrevivência Celular , Células Cultivadas , Citoproteção , Avaliação Pré-Clínica de Medicamentos , Compostos de Metilmercúrio , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Cultura Primária de Células , Ratos WistarRESUMO
BACKGROUND: We investigated the effects of ischemia followed by different periods of reperfusion (I/R) on immunoreactive S100ß-positive glial and Hu-immunoreactive neurons co-expressing the P2X2 receptor in the myenteric plexus of the rat ileum. METHODS: The ileal artery was occluded for 35 min with an atraumatic vascular clamp. The animals were killed 24 h, 72 h, and 1 week after ischemia. Sham animals were not submitted to ileal artery occlusion. The relative density, size, and co-localization of P2X2 receptor-expressing cells in relation to S100ß-immunoreactive glial and Hu-immunoreactive neuronal cells were evaluated. Additionally, we analyzed the effects of I/R on gastrointestinal transit and ileum contractile activity. RESULTS: The cellular density of P2X2 receptor and neuronal Hu immunoreactivity/cm(2) decreased after I/R, whereas glial S100ß immunoreactivity/cm(2) increased. No significant differences between sham and I/R groups were observed regarding the perikarya area of Hu-positive neurons. The area of S100ß-immunoreactive glial cells increased by 24.1 % 1 week after I/R compared with the 24 h group. Methylene blue progression along the small intestine decreased (P < 0.05) from 24.5 ± 2.3 % in the sham group to 17.2 ± 2.0 % 1 week post-ischemia. We noted a significant (P < 0.05) decrease in the maximal contraction amplitude triggered by electrical field stimulation in the presence of ATP in preparations submitted to 24 h of I/R. CONCLUSIONS: Changes in the P2X2 receptor density parallel myenteric neuronal loss following I/R of the rat ileum. This, together with the increase in the activated (oversized) glial cells, may contribute to decreased GI motility after I/R.
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Íleo/irrigação sanguínea , Músculo Liso/fisiopatologia , Plexo Mientérico/metabolismo , Neuroglia/metabolismo , Receptores Purinérgicos P2X2/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Animais , Trânsito Gastrointestinal/fisiologia , Masculino , Contração Muscular , Plexo Mientérico/imunologia , Plexo Mientérico/patologia , Neuroglia/imunologia , Neuroglia/patologia , Neurônios/imunologia , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismoRESUMO
Neuromuscular transmission is clinically monitored using the train-of-four ratio (TOFratio), which is the quotient between twitch tension produced by the fourth (T4) and by the first (T1) stimulus within a train-of-four stimulation at 2Hz. Neostigmine causes a paradoxical depression of the TOFratio (TOFfade) that is amplified by intra-arterial atropine in cats. This led us to question the usefulness of the TOFratio as a sole testing element to control neostigmine-induced reversal of neuromuscular transmission block caused by non-depolarizing agents. We hypothesized that the inhibition of cholinesterase activity might increase acetylcholine bioavailability and consequently cholinoceptor activation, leading to concomitant adenosine release from nerve endings and skeletal muscle fibers. The involvement of presynaptic muscarinic and adenosine receptors in neostigmine-induced TOFfade in the rat phrenic nerve diaphragm was investigated. Blockade of adenosine A2A receptors with ZM241385 and of muscarinic M2 receptors with methoctramine or atropine amplified neostigmine-induced TOFfade. Notwithstanding TOFfade amplification, the blockade of M2 or A2A receptors increased both T1 and T4 twitch tensions above control during the first 3min of neostigmine application. Beyond that period, the T1 twitch tension returned to baseline, whereas T4 decreased further until the control value with neostigmine alone. Blockade of M1 receptors by pirenzepine did not change neostigmine-induced TOFfade, unless A2A receptors were concurrently blocked with ZM241385. Data indicate that the paradoxical neostigmine-induced fade involves presynaptic mechanisms that regulate transmitter release and synaptic adenosine accumulation, including the activation of adenosine A2A and muscarinic M2 receptors.
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Inibidores da Colinesterase/farmacologia , Neostigmina/farmacologia , Nervo Frênico/efeitos dos fármacos , Receptores Colinérgicos/fisiologia , Receptores Purinérgicos P1/fisiologia , Animais , Atropina/farmacologia , Diaminas/farmacologia , Diafragma/efeitos dos fármacos , Diafragma/fisiologia , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/farmacologia , Nervo Frênico/fisiologia , Pirenzepina/farmacologia , Antagonistas de Receptores Purinérgicos P1/farmacologia , Ratos , Ratos Wistar , Receptores Pré-Sinápticos/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Triazinas/farmacologia , Triazóis/farmacologiaRESUMO
1. The 2 Hz train-of-four ratio (TOF(ratio)) is used to monitor the degree of patient curarization. Using a rat phrenic nerve-hemidiaphragm preparation, we showed that antinicotinic agents, such as hexamethonium, d-tubocurarine and pancuronium, but not cisatracurium, decreased contractions produced by physiological nerve activity patterns (50 Hz) more efficiently than those caused by 2 Hz trains. Uncertainty about the usefulness of the TOF(ratio) to control safe recovery from curarization prompted us to investigate the muscarinic and adenosine neuromodulation of tetanic (50 Hz) fade induced by antinicotinic agents at concentrations that cause a 25% reduction in the TOF(ratio) (TOF(fade)). 2. Tetanic fade caused by d-tubocurarine (1.1 µmol/L), pancuronium (3 µmol/L) and hexamethonium (5.47 mmol/L) was attenuated by blocking presynaptic inhibitory muscarinic M(2) and adenosine A(1) receptors with methoctramine (1 µmol/L) and 1,3-dipropyl-8-cyclopentylxanthine (2.5 nmol/L), respectively. These compounds enhanced rather than decreased tetanic fade induced by cisatracurium (2.2 µmol/L), but they consistently attenuated cisatracurium-induced TOF(fade). The effect of the M(1) receptor antagonist pirenzepine (10 nmol/L) on fade produced by antinicotinic agents at 50 Hz was opposite to that observed with TOF stimulation. Blockade of adenosine A(2A) receptors with ZM 241385 (10 nmol/L) attenuated TOF(fade) caused by all antinicotinic drugs tested, with the exception of the 'pure' presynaptic nicotinic antagonist hexamethonium. ZM 241385 was the only compound tested in this series that facilitated recovery from tetanic fade produced by cisatracurium. 3. The data suggest that distinct antinicotinic relaxants interfere with fine-tuning neuromuscular adaptations to motor nerve stimulation patterns via activation of presynaptic muscarinic and adenosine receptors. These results support the use of A(2A) receptor antagonists together with atropine to facilitate recovery from antinicotinic neuromuscular blockade.
Assuntos
Antagonistas do Receptor A2 de Adenosina/farmacologia , Bloqueadores Neuromusculares/farmacologia , Junção Neuromuscular/efeitos dos fármacos , Antagonistas Nicotínicos/farmacologia , Animais , Diafragma/efeitos dos fármacos , Diafragma/fisiologia , Sinergismo Farmacológico , Estimulação Elétrica/métodos , Hexametônio/farmacologia , Masculino , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Junção Neuromuscular/fisiologia , Pancurônio/farmacologia , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/fisiologia , Ratos , Ratos Wistar , Receptor A2A de Adenosina/metabolismo , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M2/metabolismo , Período Refratário Eletrofisiológico/efeitos dos fármacos , Tubocurarina/farmacologiaRESUMO
A seleção e o agendamento temporal inadequados dos pacientes permanecem as causas mais importantes de insucesso da cirurgia discal lombar. OBJETIVO: Este trabalho pretende avaliar os resultados clínicos e os factores preditivos que influenciam o prognóstico dos pacientes submetidos à discectomia lombar através de um modelo analítico multifatorial. MÉTODOS: Apresentamos uma série prospectiva de 68 pacientes com hérnias discais lombares que foram submetidos à discectomia entre 2003 e 2007. O seguimento médio foi de 3,9±0,1 anos. Os resultados clínicos foram avaliados utilizando o escore JOA (Japonese Orthopaedic Association Assessment Scoring System) (JOA=29). RESULTADOS: Resultados pós-operatórios bom e excelente foram obtidos em 75 por cento dos casos. Pacientes do sexo masculino e a preponderância de sintomas subjectivos sobre sintomas clínicos estiveram associados com os melhores resultados clínicos e com o retorno mais precoce à actividade laboral. O tempo de espera pela cirurgia não teve influência no resultado final. A necessidade de cirurgia foi questionada na ausência de défices neurológicos significativos (JOA para resultados clínicos >3/6). Um valor JOA pré-operatório >15 (debilidade inicial baixa) está correlacionado com piores resultados clínicos pós-operatórios. CONCLUSÕES: O escore JOA é de fácil aplicação para clínicos e pacientes, uniformiza dados subjectivos e apresenta valor preditivo para os resultados dos pacientes submetidos à discectomia lombar.
Inappropriate patient selection and timing for lumbar disc surgery are still the the major causes of failures. OBJECTIVE: We evaluated the clinical outcome and predictive factors that influence the prognosis of patients submitted to lumbar discectomy using a multivariate analysis model. METHODS: We report a prospective series of 68 patients with herniated lumbar disc who underwent limited discectomy during 2003 to 2007. The average follow-up period was 3.9±0.1 years. Clinical findings were evaluated using Japonese Orthopaedic Association Assessment Scoring System (JOA=29). RESULTS: Excellent and good postoperative improvement rates were obtained in 75 percent of the patients. Male gender and preponderance of subjective symptoms over clinical signs were associated with better clinical outcomes and faster return to work. Waiting time for surgery had no consistent effect on the outcome. The need for immediate surgery was questionable in the absence of significant neurological disturbance (JOA for clinical signs >3/6). JOA scoring had predictive value for preoperative assessment for lumbar disc surgery, i.e. preoperative JOA >15 (low initial disability) correlated with poor surgery outcome. CONCLUSIONS: JOA scoring is easily performed for patients and clinicians, standardizes subjective data and presents high predictive value of patients' outcome after lumbar discectomy.
La selección y la agenda temporal inadecuada de los enfermos permanecen como las causas más importantes de la falta de éxito en la cirugía discal lumbar. OBJETIVO: este trabajo pretende evaluar los resultados clínicos y los factores predictivos que influyen en el pronóstico de los pacientes sometidos a la discectomía lumbar por medio de un modelo analítico multifatorial. MÉTODOS: se presenta una serie prospectiva de 68 pacientes con hernias discales lumbares, los cuales fueron sometidos a la discectomía entre 2003 y 2007. El seguimiento promedio fue de 3.9±0.1 años. Los resultados clínicos fueron evaluados utilizando el JOA (Japonese Orthopaedic Association Assessment Scoring System) score (JOA=29). RESULTADOS: los resultados postoperatorios buenos y excelentes fueron obtenidos en 75 por ciento de los pacientes. Enfermos del sexo masculino y la preponderancia de síntomas subjetivos sobre síntomas clínicos estuvieron asociados con los mejores resultados clínicos y con el regreso más precoz a la actividad laboral. El tiempo de espera para la cirugía no influyó en el resultado final. La necesidad de cirugía fue cuestionada en la ausencia de déficits neurológicos significativos (JOA para resultados clínicos >3/6). Un valor JOA preoperatorio > 15 (debilidad inicial baja) está correlacionado con los peores resultados clínicos postoperatorios. CONCLUSIONES: el JOA score se presenta de fácil aplicación para clínicos y enfermos, uniformiza datos subjetivos y presenta un valor predictivo para los resultados de los pacientes sometidos a la discectomía lumbar.
Assuntos
Humanos , Deslocamento do Disco Intervertebral/cirurgia , Hérnia , Dor Lombar , Vértebras Lombares/patologiaRESUMO
This study was undertaken to investigate the mechanism by which the toxin from the bee venom, apamin, might exert beneficial effects in patients suffering from myotonic dystrophy. The effects of apamin were compared with those produced by another potassium channel blocker, 4-aminopyridine, on rat hemidiaphragm preparations stimulated at a 100 Hz frequency via the phrenic nerve. Apamin and 4-aminopyridine increased nerve-evoked tetanic fade without changing the maximal tetanic tension. The inhibitory effect of apamin was mimicked by acetylcholine. In contrast with apamin, 4-aminopyridine increased the amplitude of muscle contractions induced by nerve stimulation at 0.2 Hz frequency. All these compounds were devoid of effect when diaphragm muscle fibres were stimulated directly in the presence of the neuromuscular blocker, D-tubocurarine. The muscarinic M(2) receptor antagonist, methoctramine, prevented the inhibitory effects of both apamin and acetylcholine. Blockade of presynaptic facilitatory muscarinic M(1) and nicotinic receptors respectively with pirenzepine and hexamethonium increased apamin-induced tetanic fade. Data suggest that apamin inhibits neuromuscular transmission by a mechanism independent of the blockade of Ca(2+)-activated K(+) channels, which might involve the activation of inhibitory muscarinic M(2) receptors on motor nerve terminals. Such a mechanism may be the origin of the beneficial effect of apamin controlling muscle excitability in patients suffering from myotonic diseases.