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The increased muscular force output required for some behaviors is achieved via amplification of motoneuron output via cholinergic C-bouton synapses. Work in neonatal mouse motoneurons suggested that modulation of currents mediated by post-synaptically clustered KV2.1 channels is crucial to C-bouton amplification. By focusing on more mature motoneurons, we show that conditional knockout of KV2.1 channels minimally affects either excitability or response to exogenously applied muscarine. Similarly, unlike in neonatal motoneurons or cortical pyramidal neurons, pharmacological blockade of KV2 currents has minimal effect on mature motoneuron firing in vitro. Furthermore, in vivo amplification of electromyography activity and high-force task performance was unchanged following KV2.1 knockout. Finally, we show that KV2.2 is also expressed by spinal motoneurons, colocalizing with KV2.1 opposite C-boutons. We suggest that the primary function of KV2 proteins in motoneurons is non-conducting and that KV2.2 can function in this role in the absence of KV2.1.
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In neurological conditions affecting the brain, early-stage neural circuit adaption is key for long-term preservation of normal behaviour. We tested if motoneurons and respective microcircuits also adapt in the initial stages of disease progression in a mouse model of progressive motoneuron degeneration. Using a combination of in vitro and in vivo electrophysiology and super-resolution microscopy, we found that, preceding muscle denervation and motoneuron death, recurrent inhibition mediated by Renshaw cells is reduced in half due to impaired quantal size associated with decreased glycine receptor density. Additionally, higher probability of release from proprioceptive Ia terminals leads to increased monosynaptic excitation to motoneurons. Surprisingly, the initial impairment in recurrent inhibition is not a widespread feature of inhibitory spinal circuits, such as group I inhibitory afferents, and is compensated at later stages of disease progression. We reveal that in disease conditions, spinal microcircuits undergo specific multiphasic homeostatic compensations to preserve force output.
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PURPOSE: The present study aimed at evaluating possible synergistic effects between two risk factors for cognitive decline and neurodegenerative disorders, i.e. iron overload and exposure to a hypercaloric/hyperlipidic diet, on cognition, insulin resistance, and hippocampal GLUT1, GLUT3, Insr mRNA expression, and AKT phosporylation. METHODS: Male Wistar rats were treated with iron (30 mg/kg carbonyl iron) or vehicle (5% sorbitol in water) from 12 to 14th post-natal days. Iron-treated rats received a standard laboratory diet or a high fat diet from weaning to adulthood (9 months of age). Recognition and emotional memory, peripheral blood glucose and insulin levels were evaluated. Glucose transporters (GLUT 1 and GLUT3) and insulin signaling were analyzed in the hippocampus of rats. RESULTS: Both iron overload and exposure to a high fat diet induced memory deficits. Remarkably, the association of iron with the high fat diet induced more severe cognitive deficits. Iron overload in the neonatal period induced higher insulin levels associated with significantly higher HOMA-IR, an index of insulin resistance. Long-term exposure to a high fat diet resulted in higher fasting glucose levels. Iron treatment induced changes in Insr and GLUT1 expression in the hippocampus. At the level of intracellular signaling, both iron treatment and the high fat diet decreased AKT phosphorylation. CONCLUSION: The combination of iron overload with exposure to a high fat diet only led to synergistic deleterious effect on emotional memory, while the effects induced by iron and by the high fat diet on AKT phosphorylation were comparable. These findings indicate that there is, at least to some extent, an additive effect of iron combined with the diet. Further studies investigating the mechanisms associated to deleterious effects on cognition and susceptibility for the development of age-associated neurodegenerative disorders are warranted.
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Animales Recién Nacidos , Dieta Alta en Grasa , Transportador de Glucosa de Tipo 1 , Hipocampo , Resistencia a la Insulina , Sobrecarga de Hierro , Trastornos de la Memoria , Ratas Wistar , Animales , Masculino , Dieta Alta en Grasa/efectos adversos , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/metabolismo , Trastornos de la Memoria/etiología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratas , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 3/metabolismo , Transportador de Glucosa de Tipo 3/genética , Receptor de Insulina/metabolismo , Receptor de Insulina/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucemia/metabolismo , Insulina/sangre , Transducción de SeñalRESUMEN
Neurophysiological methods are used widely to gain information about motor neuron excitability and axon conduction in neurodegenerative diseases. The F-wave is a common biomarker used to test motor neuron properties in the diagnosis of neurological diseases. Although the origin of the F-wave is a subject of debate, the most widely accepted mechanism posits that the F-wave is generated by the backfiring of motor neurons stimulated antidromically from the periphery. In this study, we developed an ex vivo mouse sciatic nerve-attached spinal cord preparation with sensory axons severed. In this preparation, stimulation of the whole sciatic nerve or its tibial branch evoked responses with the electrophysiological signatures of F-waves. Manipulations of synaptic transmission by either removal of extracellular calcium or block of post-synaptic glutamate receptors abolished these responses. These results suggest that F-waves are mediated by spinal microcircuits activated by recurrent motor axon collaterals via glutamatergic synapses.
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Enfermedades del Sistema Nervioso , Fenómenos Fisiológicos del Sistema Nervioso , Animales , Ratones , Neuronas Motoras/fisiología , Transmisión Sináptica , Sinapsis , Médula Espinal , Estimulación EléctricaRESUMEN
Dystonia, a neurological disorder defined by abnormal postures and disorganized movements, is considered to be a neural circuit disorder with dysfunction arising within and between multiple brain regions. Given that spinal neural circuits constitute the final pathway for motor control, we sought to determine their contribution to this movement disorder. Focusing on the most common inherited form of dystonia in humans, DYT1-TOR1A, we generated a conditional knockout of the torsin family 1 member A (Tor1a) gene in the mouse spinal cord and dorsal root ganglia (DRG). We found that these mice recapitulated the phenotype of the human condition, developing early-onset generalized torsional dystonia. Motor signs emerged early in the mouse hindlimbs before spreading caudo-rostrally to affect the pelvis, trunk, and forelimbs throughout postnatal maturation. Physiologically, these mice bore the hallmark features of dystonia, including spontaneous contractions at rest and excessive and disorganized contractions, including cocontractions of antagonist muscle groups, during voluntary movements. Spontaneous activity, disorganized motor output, and impaired monosynaptic reflexes, all signs of human dystonia, were recorded from isolated mouse spinal cords from these conditional knockout mice. All components of the monosynaptic reflex arc were affected, including motor neurons. Given that confining the Tor1a conditional knockout to DRG did not lead to early-onset dystonia, we conclude that the pathophysiological substrate of this mouse model of dystonia lies in spinal neural circuits. Together, these data provide new insights into our current understanding of dystonia pathophysiology.
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Distonía Muscular Deformante , Distonía , Humanos , Ratones , Animales , Distonía/genética , Distonía/metabolismo , Distonía Muscular Deformante/genética , Distonía Muscular Deformante/metabolismo , Ratones Noqueados , Encéfalo/metabolismo , Chaperonas Moleculares/metabolismoRESUMEN
The highly differentiated anuran larvae make them an interesting and complementary source of information to understand anuran evolution. Among neotropical foam-nesting frogs, the available information on tadpole morphology for the subfamily Leiuperinae remains largely incomplete and variably reported among genera; in the monophyletic genus Engystomops it is still incipient. Herein, we summarize available information on larval morphology for five of the nine known species of Engystomops, three of them for the first time, reporting external morphology, buccopharyngeal cavity, and skeleton. The tadpoles of the genus have an overall generalized morphology and many traits are conserved across species. Nevertheless, many characters are systematically informative and some are diagnostic for some species, as the paravertebral gland in Engystomops petersi and the dorsally directed spiracle in Engystomops puyango. Other characters provide support for some subclades within the genus. Moreover, some traits, such as the direction of the vent tube, supports the close relationship between Engystomops and Physalaemus, whereas other support the existence of these two as distinct genera, such as the overall shape of the lateral ridge papillae and the presence of a processus pseudopterygoideus.
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Anuros , Animales , Anuros/anatomía & histología , Brasil , Larva/anatomía & histología , FilogeniaRESUMEN
In vitro spinal cord preparations have been extensively used to study microcircuits involved in the control of movement. By allowing precise control of experimental conditions coupled with state-of-the-art genetics, imaging, and electrophysiological techniques, isolated spinal cords from mice have been an essential tool in detailing the identity, connectivity, and function of spinal networks. The majority of the research has arisen from in vitro spinal cords of neonatal mice, which are still undergoing important postnatal maturation. Studies from adults have been attempted in transverse slices, however, these have been quite challenging due to the poor motoneuron accessibility and viability, as well as the extensive damage to the motoneuron dendritic trees. In this work, we describe two types of coronal spinal cord preparations with either the ventral or the dorsal horn ablated, obtained from mice of different postnatal ages, spanning from preweaned to 1 mo old. These semi-intact preparations allow recordings of sensory-afferent and motor-efferent responses from lumbar motoneurons using whole cell patch-clamp electrophysiology. We provide details of the slicing procedure and discuss the feasibility of whole cell recordings. The in vitro dorsal and ventral horn-ablated spinal cord preparations described here are a useful tool to study spinal motor circuits in young mice that have reached the adult stages of locomotor development.NEW & NOTEWORTHY In the past 20 years, most of the research into the mammalian spinal circuitry has been limited to in vitro preparations from embryonic and neonatal mice. We describe two in vitro longitudinal lumbar spinal cord preparations from juvenile mice that allow the study of motoneuron properties and respective afferent or efferent spinal circuits through whole cell patch clamp. These preparations will be useful to those interested in the study of microcircuits at mature stages of motor development.
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Neuronas Motoras , Médula Espinal , Animales , Fenómenos Electrofisiológicos , Región Lumbosacra , Mamíferos , Ratones , Neuronas Motoras/fisiología , Técnicas de Placa-Clamp , Médula Espinal/fisiología , Asta Dorsal de la Médula EspinalRESUMEN
The genus Edalorhina consists of two species of small forest-floor frogs inhabiting the Amazon basin. The tadpole of Edalorhina perezi, the most widely distributed species, was previously described based on a single and early stage (Gosner 25) individual. Herein, we provide a description of the tadpole in Gosner stages 35-36 including internal morphology data (i.e., buccopharyngeal cavity and larval skeleton) based on samples from two populations from Ecuador. Edalorhina shares a generalized morphology with most members of its closely related taxa; however, it is distinguished from the other species by having an almost terminal oral disc. The presence of a dextral vent tube is considered a synapomorphy for the clade consisting of Edalorhina, Engystomops, and Physalaemus. Within this clade, the combination of two lingual papillae, a filiform median ridge, and the lack of buccal roof papillae are diagnostic of E. perezi and putative autapomorphies of Edalorhina. Chondrocranial anatomy provides characteristics, that is, presence of and uniquely shaped processus pseudopterygoideus and cartilago suprarostralis with corpora and alae joined by dorsal and ventral connections that readily differentiates the genus from other Leiuperinae.
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Anuros/anatomía & histología , Boca/anatomía & histología , Cráneo/anatomía & histología , Animales , Brasil , Larva/anatomía & histología , Larva/ultraestructura , Boca/ultraestructura , Filogenia , Cráneo/ultraestructura , Especificidad de la EspecieRESUMEN
OBJECTIVES: To assess the attitudes, knowledge, and experiences of Brazilian resident physicians regarding religiosity/spirituality (R/S), factors associated with addressing this issue, and its influence on clinical practice. METHODS: We report results of the multicenter "Spirituality in Brazilian Medical Residents" (SBRAMER) study involving 7 Brazilian university centers. The Network for Research Spirituality and Health (NERSH) scale (collecting sociodemographic data, opinions about the R/S-health interface, and respondents' R/S characteristics) and the Duke Religion Index were self-administered. Logistic regression models were constructed to determine those factors associated with residents' opinions on spirituality in clinical practice. RESULTS: The sample comprised 879 resident physicians (53.5% of total) from all years of residency with 71.6% from clinical specialties. In general, the residents considered themselves spiritual and religious, despite not regularly attending religious services. Most participants believed R/S had an important influence on patient health (75.2%) and that it was appropriate to discuss these beliefs in clinical encounters with patients (77.1%), although this was not done in routine clinical practice (14.4%). The main barriers to discussing R/S were maintaining professional neutrality (31.4%), concern about offending patients (29.1%), and insufficient time (26.2%). Factors including female gender, clinical specialty (e.g., internal medicine, family medicine, psychiatry) as opposed to surgical specialty (e.g., surgery, obstetrics/gynecology, orthopedics), having had formal training on R/S, and higher levels of R/S were associated with greater discussion of and more positive opinions about R/S. CONCLUSION: Brazilian resident physicians held that religious and spiritual beliefs can influence health, and deemed it appropriate for physicians to discuss this issue. However, lack of training was one of the main obstacles to addressing R/S issues in clinical practice. Educators should draw on these data to conduct interventions and produce content on the subject in residency programs.
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Médicos , Espiritualidad , Brasil , Estudios Transversales , Femenino , Humanos , Religión , Encuestas y CuestionariosRESUMEN
The Neotropical foam-nesting genus Leptodactylus Fitzinger is currently composed of 75 species (Frost 2019) divided into four monophyletic species groups (De Sá et al. 2014). The L. melanonotus species group includes 17 species delimited by five adult osteological character-states (De Sá et al. 2014). Leptodactylus natalensis Lutz is the only species of the L. melanonotus species group that occurs in north of the Brazilian Atlantic Rain Forest (De Sá et al. 2014; Almeida et al. 2016) and whose type locality is the municipality of Natal, state of Rio Grande do Norte, Brazil (Lutz 1930). The tadpole of this species was briefly described by Oliveira Lírio-Júnior (2000) based on a single individual from the municipality of Aracaju, state of Sergipe, Brazil. Herein, we present a complete redescription of the tadpole of this species, including morphometric data and interpopulational variation. Besides, we provide comparisons with all members of the L. melanonotus group.
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Anuros , Bosques , Animales , Brasil , Larva , Bosque LluviosoRESUMEN
Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno-electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system-specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.
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Canal de Sodio Activado por Voltaje NAV1.7/genética , Células del Asta Posterior/fisiología , Células Receptoras Sensoriales/fisiología , Animales , Fenómenos Electrofisiológicos , Potenciales Postsinápticos Excitadores , Expresión Génica , Inmunohistoquímica , Ratones , Ratones Noqueados , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Células del Asta Posterior/efectos de los fármacos , Células del Asta Posterior/ultraestructura , Células Receptoras Sensoriales/efectos de los fármacos , Células Receptoras Sensoriales/ultraestructura , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacologíaRESUMEN
Spinal motor networks are formed by diverse populations of interneurons that set the strength and rhythmicity of behaviors such as locomotion. A small cluster of cholinergic interneurons, expressing the transcription factor Pitx2, modulates the intensity of muscle activation via 'C-bouton' inputs to motoneurons. However, the synaptic mechanisms underlying this neuromodulation remain unclear. Here, we confirm in mice that Pitx2+ interneurons are active during fictive locomotion and that their chemogenetic inhibition reduces the amplitude of motor output. Furthermore, after genetic ablation of cholinergic Pitx2+ interneurons, M2 receptor-dependent regulation of the intensity of locomotor output is lost. Conversely, chemogenetic stimulation of Pitx2+ interneurons leads to activation of M2 receptors on motoneurons, regulation of Kv2.1 channels and greater motoneuron output due to an increase in the inter-spike afterhyperpolarization and a reduction in spike half-width. Our findings elucidate synaptic mechanisms by which cholinergic spinal interneurons modulate the final common pathway for motor output.
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Neuronas Colinérgicas/fisiología , Interneuronas/fisiología , Locomoción/fisiología , Neuronas Motoras/fisiología , Sinapsis/fisiología , Animales , Femenino , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/fisiología , Ratones , Ratones Endogámicos C57BL , Canales de Potasio Shab/metabolismo , Canales de Potasio Shab/fisiología , Factores de Transcripción/metabolismo , Factores de Transcripción/fisiología , Proteína del Homeodomínio PITX2RESUMEN
Neuromodulation ensures that neural circuits produce output that is flexible whilst remaining within an optimal operational range. The neuromodulator acetylcholine is released during locomotion to regulate spinal motor circuits. However, the range of receptors and downstream mechanisms by which acetylcholine acts have yet to be fully elucidated. We therefore investigated metabotropic acetylcholine receptor-mediated modulation by using isolated spinal cord preparations from neonatal mice in which locomotor-related output can be induced pharmacologically. We report that M2 receptor blockade decreases the frequency and amplitude of locomotor-related activity, whilst reducing its variability. In contrast, M3 receptor blockade destabilizes locomotor-related bursting. Motoneuron recordings from spinal cord slices revealed that activation of M2 receptors induces an outward current, decreases rheobase, reduces the medium afterhyperpolarization, shortens spike duration and decreases synaptic inputs. In contrast, M3 receptor activation elicits an inward current, increases rheobase, extends action potential duration and increases synaptic inputs. Analysis of miniature postsynaptic currents support that M2 and M3 receptors modulate synaptic transmission via different mechanisms. In summary, we demonstrate that M2 and M3 receptors have opposing modulatory actions on locomotor circuit output, likely reflecting contrasting cellular mechanisms of action. Thus, intraspinal cholinergic systems mediate balanced, multimodal control of spinal motor output.
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Acetilcolina/metabolismo , Locomoción/fisiología , Neuronas Motoras/metabolismo , Receptor Muscarínico M2/metabolismo , Receptor Muscarínico M3/metabolismo , Médula Espinal/metabolismo , Acetilcolina/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Animales Recién Nacidos , Diaminas/farmacología , Técnicas In Vitro , Ratones , Ratones Endogámicos C57BL , Neuronas Motoras/fisiología , Muscarina/farmacología , Piperidinas/farmacología , Receptor Muscarínico M2/antagonistas & inhibidores , Receptor Muscarínico M2/fisiología , Receptor Muscarínico M3/antagonistas & inhibidores , Receptor Muscarínico M3/fisiología , Médula Espinal/fisiologíaRESUMEN
BACKGROUND: The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). The generation of cortisol from this reaction may increase intra-abdominal cortisol levels and contribute to the physiopathogenesis of obesity and metabolic syndrome (MetS). The relationship of HSD11B1 rs45487298 and H6PD rs6688832 polymorphisms with obesity and MetS was studied. We also studied how HSD11B1 abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) gene expression is related to body fat distribution. METHODS: Rates of obesity and MetS features were cross-sectionally analyzed according to these polymorphisms in 1006 Brazilian white patients with type 2 diabetes (T2DM). Additionally, HSD11B1 expression was analyzed in VAT and SAT in a different cohort of 28 participants with and without obesity who underwent elective abdominal operations. RESULTS: Although polymorphisms of the two genes were not individually associated with MetS features, a synergistic effect was observed between both. Carriers of at least three minor alleles exhibited lower BMI compared to those with two or fewer minor alleles adjusting for gender and age (27.4 ± 4.9 vs. 29.3 ± 5.3 kg/m2; P = 0.005; mean ± SD). Obesity frequency was also lower in the first group (24.4% vs. 41.6%, OR = 0.43, 95% CI 0.21-0.87; P = 0.019). In the second cohort of 28 subjects, HSD11B1 gene expression in VAT was inversely correlated with BMI (r = - 0.435, P = 0.034), waist circumference (r = - 0.584, P = 0.003) and waist-to-height ratio (r = - 0.526, P = 0.010). CONCLUSIONS: These polymorphisms might interact in the protection against obesity in T2DM individuals. Obese individuals may have decreased intra-abdominal VAT HSD11B1 gene expression resulting in decreasing intra-abdominal cortisol levels as a compensatory mechanism against central and general adiposity.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron (MN) loss. Recent evidences highlight astrocytes as important players in MN death, but the mechanism-based neurotoxicity is still unknown. It is also unclear whether activation of astrocytes in ALS occurs differently in the cerebral cortex and spinal cord. We investigated glial and neuronal alterations in the cortex of SOD1G93A (mSOD1) mice in pre-symptomatic and symptomatic stages. We also characterized astrocytes isolated from the cortex of 7-day-old mSOD1 mice for their aberrancy and MN-induced degenerative effects. In the early stage, we identified a reduction of cell proliferation, NF-kB expression, and of vimentin and micro(miR)-146a expression, suggesting a restrained cortical inflammatory status. However, increased NF-kB expression, cell proliferation, and gene expression of HMGB1, connexin 43 and S100B were distinctive of the symptomatic stage, together with MN loss, downregulated unfold protein response, and decreased expression of synaptic proteins, together with that of miR-125b, miR-21, miR-146a, GFAP, and glutamate transporters. Astrocytes cultured for 13 days in vitro showed comparable NF-kB expression and cell proliferation increase, as well as similar microRNA and gene/protein expression profiles (decreased miR-21, miR-146a, GLT-1 and GFAP, and upregulated HMGB1, S100B and connexin-43), thus sustaining astrocytes as the major contributors of cortical homeostasis deregulation in the symptomatic stage. These reactive astrocytes reduced neurite length and synaptophysin expression in NSC-34/hSOD1WT MN-like cells, and induced mitochondria dysfunction, PSD-95 downregulation, metalloproteinase-9 activation, and late apoptosis in NSC-34/hSOD1G93A cells. Data indicate that astrocytes in mSOD1 mice model acquire early phenotypic aberrancies and highlight downregulated miR-146a as a biomarker and drug target in ALS.
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Esclerosis Amiotrófica Lateral/metabolismo , Astrocitos/metabolismo , Corteza Cerebral/metabolismo , Gliosis/metabolismo , MicroARNs/metabolismo , Esclerosis Amiotrófica Lateral/patología , Animales , Astrocitos/patología , Biomarcadores/metabolismo , Corteza Cerebral/patología , Modelos Animales de Enfermedad , Gliosis/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Transgénicos , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Proyección Neuronal/fisiología , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismoRESUMEN
Layering of neural circuits facilitates the separation of neurons with high spatial sensitivity from those that play integrative temporal roles. Although anatomical layers are readily identifiable in the brain, layering is not structurally obvious in the spinal cord. But computational studies of motor behaviors have led to the concept of layered processing in the spinal cord. It has been postulated that spinal V3 interneurons (INs) play multiple roles in locomotion, leading us to investigate whether they form layered microcircuits. Using patch-clamp recordings in combination with holographic glutamate uncaging, we demonstrate focal, layered modules, in which ventromedial V3 INs form synapses with one another and with ventrolateral V3 INs, which in turn form synapses with ipsilateral motoneurons. Motoneurons, in turn, provide recurrent excitatory, glutamatergic input to V3 INs. Thus, ventral V3 interneurons form layered microcircuits that could function to ensure well-timed, spatially specific movements.
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Interneuronas/fisiología , Neuronas Motoras/fisiología , Médula Espinal/fisiología , Animales , RatonesRESUMEN
Este estudo avalia a política do Ministério do Trabalho e Emprego (MTE) para reduzir a incidência de acidentes de trabalho típicos registrados na construção civil do município de São Paulo, entre 2002 e 2011. A partir dos dados contidos no Sistema Federal de Inspeção do Trabalho (SFIT), analisam-se as ações dos auditores-fiscais do trabalho em reduzir a reincidência do desrespeito à saúde e à segurança dos trabalhadores por parte dos empregadores, nos canteiros de obra, comparando-se, ao cabo, os resultados de duas práticas: a conciliadora e a penalização ao comportamento ilegal do infrator. Se tais ações contribuíram para reduzir a persistência dos empregadores nas práticas geradoras da maioria absoluta acidentes de trabalho, especialmente entre 2002 e 2009, de forma concreta, as fiscalizações com autos de infração mostraram-se mais efetivas. Por conseguinte, discute-se a alternativa de aplicá-los face à tese da pedagogia de conciliação como estímulo institucional da inspeção ao empregador, considerando-se que os resultados estatísticos obtidos para um período de dez anos sugerem a pertinência de se coibir ao tempo e à hora o comportamento impune.
This study evaluates Brazil´s Labor Ministry policy for reducing the incidence of typical building construction occupational accidents registered in São Paulo City during the years 2002-2011. Using data extracted from the Labor Inspectorate Federal System (SFIT), the labor inspectors actions aimed at reducing the reoccurrence of employer disrespect for OSH on construction sites were analyzed. The results between two inspectorate methods were compared: conciliatory and punitive. Such actions helped decrease employer persistence in allowing most of the factors generating occupational accidents, mainly between 2002-2009, with the inspectorate actions using fines being more effective. Consequently this article discusses the alternative to applying the conciliatory method as an institutional incentive, from the labor inspectorate to employers, considering that statistical results obtained from a decade of data suggest the relevance of restraining the unpunished behavior.
Este estudio evalúa la política del Ministerio de Trabajo para reducir la incidencia de accidentes en la construcción civil en el municipio de São Paulo, entre 2002 y 2011. Se trata de una investigación en la que se analizan las acciones de los auditores fiscales del trabajo para reducir el incumplimiento patronal a la salud y a la seguridad de los trabajadores. Se comparan los resultados de dos prácticas: la conciliadora y la penalización al comportamiento ilegal del infractor. Entre 2002 y 2009, concretamente, las fiscalizaciones con autos de infracción se mostraron más efectivas. Por lo tanto, se discute la alternativa de aplicarlos ante la tesis de la pedagogía de conciliación como estímulo institucional de la Auditoría Fiscal del Trabajo al empleador, considerando que los resultados estadísticos obtenidos para un período de diez años sugieren la pertinencia de cohibirse al tiempo y a la hora el comportamiento impune.
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Objetivos: revisar a prevalência, a etiologia, o diagnóstico e o tratamento da rinossinusite aguda. A rinossinusite aguda é uma doença comum de prevalência mundial, caracterizada por uma inflamação da cavidade nasal e dos seios paranasais, podendo ter origem fúngica, viral ou bacteriana. Os sintomas são principalmente obstrução e secreção nasal, porém a sintomatologia pode ser ampla. Consequentemente, a correta identificação e manejo torna essa patologia um desafio na prática clínica. Metodologia: Foi realizado uma busca nas bases de dados Medline/ Pubmed e LILACS no mês de maio de 2018, incluindo artigos publicados em inglês ou português nos últimos 5 anos. Foram utilizados os seguintes descritores: "acute rhinosinusitis", "rhinitis" e "sinusitis". Os artigos foram selecionados com busca direta, considerando relevância do tema à proposta e fator de impacto. Resultados: De 228 publicações, 10 foram selecionadas, demonstrando que a rinossinusite aguda é uma doença cuja incidência ainda não está bem definida, mas é maior em indivíduos com idade entre 12 e 17 anos em relação à população geral, com prevalência de etiologia viral. Conclusão: A rinossinusite aguda é uma doença com alta incidência. O diagnóstico é predominantemente clínico, mas em casos restritos há exames de imagem, sendo o tratamento sempre sintomático.
Objectives: To review the prevalence, etiology, diagnosis and treatment of acute rhinosinusitis. Acute rhinosinusitis is a common global disease characterized by inflammation of the nasal cavity and paranasal sinuses, which may be of fungal, viral or bacterial origin. The symptoms are mainly obstruction and nasal secretion, but the symptomatology can be ample. Methodology: The search was performed in the Medline / Pubmed and LILACS databases in May 2018, including articles published in English or Portuguese in the last 5 years. The following descriptors were used: "acute rhinosinusitis", "rhinitis" and "sinusitis". The articles were selected with direct search, considering relevance of the theme to the proposal and impact factor. Results: Of 228 publications, 10 were selected, demonstrating that acute rhinosinusitis is a disease whose incidence is still not well defined, but is higher in individuals aged 12 to 17 years in relation to the general population, with a prevalence of viral etiology. Conclusion: Acute rhinosinusitis is a disease with a high incidence. The diagnosis is predominantly clinical, but in restricted cases there are imaging tests, and the treatment is always symptomatic.
Asunto(s)
Enfermedad Aguda , Sinusitis , Infecciones Bacterianas/tratamiento farmacológico , Virosis/tratamiento farmacológico , RinitisRESUMEN
Alveolar macrophages play a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Monocytes are recruited from blood during inflammation and then mature into alveolar macrophages. The aim of this study was to investigate the effect of cigarette smoke (CS) at different times in lung macrophages and monocytes from blood and bone marrow in mice. Male mice (C57BL/6, n = 45) were divided into groups: control, CS 5 days, CS 14 days and CS 30 days. Five days' CS exposure induced a pronounced influx of neutrophils and macrophages in the lung associated with increased levels of keratinocyte chemoattractant (KC), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and matrix metalloproteinase (MMP)-12. After 14 days of CS exposure, neutrophil recruitment and cytokine production were greatly reduced. Moreover, chronic CS exposure led to increased recruitment of macrophages (with high expression of CD206), transforming growth factor-ß (TGF-ß) production as well as no detection of TNF-α, interleukin (IL)-6 and KC. CS can also change the monocyte phenotype in the blood and bone marrow, with an increase in Ly6Clow cells. These results show for the first time that CS can change not only macrophage polarization but also monocyte. These results suggest that continued recruitment of Ly6Clow monocytes may help the distinct renewing macrophage M2 population required for COPD progression.
Asunto(s)
Pulmón/metabolismo , Macrófagos/metabolismo , Monocitos/metabolismo , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/etiología , Contaminación por Humo de Tabaco/efectos adversos , Animales , Interleucina-6/genética , Interleucina-6/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Pulmón/patología , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/genética , Lectinas de Unión a Manosa/metabolismo , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Ubiquitously expressed sodium pumps are best known for maintaining the ionic gradients and resting membrane potential required for generating action potentials. However, activity- and state-dependent changes in pump activity can also influence neuronal firing and regulate rhythmic network output. Here we demonstrate that changes in sodium pump activity regulate locomotor networks in the spinal cord of neonatal mice. The sodium pump inhibitor, ouabain, increased the frequency and decreased the amplitude of drug-induced locomotor bursting, effects that were dependent on the presence of the neuromodulator dopamine. Conversely, activating the pump with the sodium ionophore monensin decreased burst frequency. When more "natural" locomotor output was evoked using dorsal-root stimulation, ouabain increased burst frequency and extended locomotor episode duration, whereas monensin slowed and shortened episodes. Decreasing the time between dorsal-root stimulation, and therefore interepisode interval, also shortened and slowed activity, suggesting that pump activity encodes information about past network output and contributes to feedforward control of subsequent locomotor bouts. Using whole-cell patch-clamp recordings from spinal motoneurons and interneurons, we describe a long-duration (â¼60 s), activity-dependent, TTX- and ouabain-sensitive, hyperpolarization (â¼5 mV), which is mediated by spike-dependent increases in pump activity. The duration of this dynamic pump potential is enhanced by dopamine. Our results therefore reveal sodium pumps as dynamic regulators of mammalian spinal motor networks that can also be affected by neuromodulatory systems. Given the involvement of sodium pumps in movement disorders, such as amyotrophic lateral sclerosis and rapid-onset dystonia parkinsonism, knowledge of their contribution to motor network regulation also has considerable clinical importance. SIGNIFICANCE STATEMENT: The sodium pump is ubiquitously expressed and responsible for at least half of total brain energy consumption. The pumps maintain ionic gradients and the resting membrane potential of neurons, but increasing evidence suggests that activity- and state-dependent changes in pump activity also influence neuronal firing. Here we demonstrate that changes in sodium pump activity regulate locomotor output in the spinal cord of neonatal mice. We describe a sodium pump-mediated afterhyperpolarization in spinal neurons, mediated by spike-dependent increases in pump activity, which is affected by dopamine. Understanding how sodium pumps contribute to network regulation and are targeted by neuromodulators, including dopamine, has clinical relevance due to the role of the sodium pump in diseases, including amyotrophic lateral sclerosis, parkinsonism, epilepsy, and hemiplegic migraine.