Efeitos do debilitamento dos músculos oblíquos na correção cirúrgica da esotropia

Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, 2016.

Theoretical investigation of intra- and inter-cellular spatiotemporal calcium patterns in microcirculation

Microcirculatory vessels are lined by endothelial cells (ECs) which are surrounded by a single or multiple layer of smooth muscle cells (SMCs). Spontaneous and agonist induced spatiotemporal calcium (Ca2+) events are generated in ECs and SMCs, and regulated by complex bi-directional signaling between the two layers which ultimately determines the vessel tone. The contractile state of microcirculatory vessels is an important factor in the determination of vascular resistance, blood flow and blood pressure. This dissertation presents theoretical insights into some of the important and currently unresolved phenomena in microvascular tone regulation. Compartmental and continuum models of isolated EC and SMC, coupled EC-SMC and a multi-cellular vessel segment with deterministic and stochastic descriptions of the cellular components were developed, and the intra- and inter-cellular spatiotemporal Ca2+ mobilization was examined.^ Coupled EC-SMC model simulations captured the experimentally observed localized subcellular EC Ca2+ events arising from the opening of EC transient receptor vanilloid 4 (TRPV4) channels and inositol triphosphate receptors (IP3Rs). These localized EC Ca2+ events result in endothelium-derived hyperpolarization (EDH) and Nitric Oxide (NO) production which transmit to the adjacent SMCs to ultimately result in vasodilation. The model examined the effect of heterogeneous distribution of cellular components and channel gating kinetics in determination of the amplitude and spread of the Ca2+ events. The simulations suggested the necessity of co-localization of certain cellular components for modulation of EDH and NO responses. Isolated EC and SMC models captured intracellular Ca2+ wave like activity and predicted the necessity of non-uniform distribution of cellular components for the generation of Ca2+ waves. The simulations also suggested the role of membrane potential dynamics in regulating Ca2+ wave velocity. The multi-cellular vessel segment model examined the underlying mechanisms for the intercellular synchronization of spontaneous oscillatory Ca2+ waves in individual SMC. ^ From local subcellular events to integrated macro-scale behavior at the vessel level, the developed multi-scale models captured basic features of vascular Ca2+ signaling and provide insights for their physiological relevance. The models provide a theoretical framework for assisting investigations on the regulation of vascular tone in health and disease.^

First molecular determination of herpesvirus from two mysticete species stranded in the Mediterranean Sea

BACKGROUND Herpesvirus can infect a wide range of animal species: mammals, birds, reptiles, fish, amphibians and bivalves. In marine mammals, several alpha- and gammaherpesvirus have been identified in some cetaceans and pinnipeds species. To date, however, this virus has not been detected in any member of the Balaenoptera genus. CASE PRESENTATION Herpesvirus was determined by molecular methods in tissue samples from a male fin whale juvenile (Balaenoptera physalus) and a female common minke whale calf (Balaenoptera acutorostrata) stranded on the Mediterranean coast of the Region of Valencia (Spain). Samples of skin and penile mucosa from the fin whale and samples of skin, muscle and central nervous system tissue from the common minke whale tested positive for herpesvirus based on sequences of the DNA polymerase gene. Sequences from fin whale were identical and belonged to the Alphaherpesvirinae subfamily. Only members of the Gammaherpesvirinae subfamily were amplified from the common minke whale, and sequences from the muscle and central nervous system were identical. Sequences in GenBank most closely related to these novel sequences were viruses isolated from other cetacean species, consistent with previous observations that herpesviruses show similar phylogenetic branching as their hosts. CONCLUSIONS To our knowledge, this is the first molecular determination of herpesvirus in the Balaenoptera genus. It shows that herpesvirus should be included in virological evaluation of these animals.

Diaphragm muscle adaptation to sustained hypoxia: lessons from animal models with relevance to high altitude and chronic respiratory diseases

The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF) and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function.

Chronic sustained hypoxia-induced redox remodeling causes contractile dysfunction in mouse sternohyoid muscle

Chronic sustained hypoxia (CH) induces structural and functional adaptations in respiratory muscles of animal models, however the underlying molecular mechanisms are unclear. This study explores the putative role of CH-induced redox remodeling in a translational mouse model, with a focus on the sternohyoid—a representative upper airway dilator muscle involved in the control of pharyngeal airway caliber. We hypothesized that exposure to CH induces redox disturbance in mouse sternohyoid muscle in a time-dependent manner affecting metabolic capacity and contractile performance. C57Bl6/J mice were exposed to normoxia or normobaric CH (FiO2 = 0.1) for 1, 3, or 6 weeks. A second cohort of animals was exposed to CH for 6 weeks with and without antioxidant supplementation (tempol or N-acetyl cysteine in the drinking water). Following CH exposure, we performed 2D redox proteomics with mass spectrometry, metabolic enzyme activity assays, and cell-signaling assays. Additionally, we assessed isotonic contractile and endurance properties ex vivo. Temporal changes in protein oxidation and glycolytic enzyme activities were observed. Redox modulation of sternohyoid muscle proteins key to contraction, metabolism and cellular homeostasis was identified. There was no change in redox-sensitive proteasome activity or HIF-1α content, but CH decreased phospho-JNK content independent of antioxidant supplementation. CH was detrimental to sternohyoid force- and power-generating capacity and this was prevented by chronic antioxidant supplementation. We conclude that CH causes upper airway dilator muscle dysfunction due to redox modulation of proteins key to function and homeostasis. Such changes could serve to further disrupt respiratory homeostasis in diseases characterized by CH such as chronic obstructive pulmonary disease. Antioxidants may have potential use as an adjunctive therapy in hypoxic respiratory disease.

Chronic intermittent hypoxia increases rat sternohyoid muscle NADPH oxidase expression with attendant modest oxidative stress

Chronic intermittent hypoxia (CIH) causes upper airway muscle dysfunction. We hypothesized that the superoxide generating NADPH oxidase (NOX) is upregulated in CIH-exposed muscle causing oxidative stress. Adult male Wistar rats were exposed to intermittent hypoxia (5% O2 at the nadir for 90 s followed by 210 s of normoxia), for 8 h per day for 14 days. The effect of CIH exposure on the expression of NOX subunits, total myosin and 4-hydroxynonenal (4-HNE) protein adducts in sternohyoid muscle was determined by western blotting and densitometry. Sternohyoid protein free thiol and carbonyl group contents were determined by 1D electrophoresis using specific fluorophore probes. Aconitase and glutathione reductase activities were measured as indices of oxidative stress. HIF-1α content and key oxidative and glycolytic enzyme activities were determined. Contractile properties of sternohyoid muscle were determined ex vivo in the absence and presence of apocynin (putative NOX inhibitor). We observed an increase in NOX 2 and p47 phox expression in CIH-exposed sternohyoid muscle with decreased aconitase and glutathione reductase activities. There was no evidence, however, of increased lipid peroxidation or protein oxidation in CIH-exposed muscle. CIH exposure did not affect sternohyoid HIF-1α content or aldolase, lactate dehydrogenase, or glyceraldehyde-3-phosphate dehydrogenase activities. Citrate synthase activity was also unaffected by CIH exposure. Apocynin significantly increased sternohyoid force and power. We conclude that CIH exposure upregulates NOX expression in rat sternohyoid muscle with concomitant modest oxidative stress but it does not result in a HIF-1α-dependent increase in glycolytic enzyme activity. Constitutive NOX activity decreases sternohyoid force and power. Our results implicate NOX-dependent reactive oxygen species in CIH-induced upper airway muscle dysfunction which likely relates to redox modulation of key regulatory proteins in excitation-contraction coupling.

Mcardle disease: Update of reported mutations and polymorphisms in the Pygm gene

McArdle disease is an autosomal recessive disorder caused by inherited deficiency of the muscle isoform of glycogen phosphorylase (or ‘myophosphorylase´), which catalyzes the first step of glycogen catabolism, releasing glucose-1-phosphate from glycogen deposits. As a result, muscle metabolism is impaired, leading to different degrees of exercise intolerance. Patients range from asymptomatic to severely affected, including in some cases limitations in activities of daily living. The PYGM gene codifies myophosphoylase and to date 147 pathogenic mutations and 39 polymorphisms have been reported. Exon 1 and 17 are mutational hot-spots in PYGM and 50% of the described mutations are missense.

Efectos del tipo de recuperación sobre la oxigenación muscular durante el ejercicio de sentadilla

El objetivo de esta investigación es comprobar los cambios en la oxigenación muscular del recto anterior durante la realización del ejercicio de sentadilla según el tipo de recuperación. Para ello, 11 sujetos varones bien entrenados fueron distribuidos aleatoriamente a tres grupos experimentales: grupo que realiza recuperación pasiva con 2 minutos de descanso (GC), grupo que realiza recuperación activa hasta la estabilización de oxígeno (GA), grupo que realiza recuperación pasiva hasta la estabilización de oxígeno (GP). Todos realizaron la sentadilla hasta los 90º al 65% del 1RM con un 80% del carácter del esfuerzo (CE) (4x10). Los resultados muestran que el tiempo de reoxigenación (TrecSmO2) fue inferior significativamente en GA (77,94 ± 11,08) que en GC (p<0.001). En las inclinaciones medias de ejecución y reoxigenación el GA obtuvo los menores y mayores valores respectivamente y de forma significativa respecto a GC (p<0.001). Estas dos variables obtuvieron una relación inversamente proporcional con una r=-0.9585 (p<0.001). Estos resultados muestran una mejor reoxigenación en el grupo que realizó descanso de forma activa. Se muestra una relación inversamente proporcional entre la inclinaciones de ejecución y recuperación por lo que cuanto más rápida y completa sea la desoxigenación más lenta resultará la reoxigenación. Además, la saturación de oxígeno puede ser un factor de la fatiga neuromuscular y su control durante el entrenamiento de fuerza podría facilitar los objetivos de entrenamiento. Estos resultados muestran, a priori, una mejor recuperación entre series a nivel oxidativo cuando los sujetos realizan una recuperación de forma activa, en comparación con la pasiva.

Patologías lumbares: determinación de los factores ocupacionales y carga prestacional en una entidad promotora de salud en Bogotá

Resumen: Introducción El dolor lumbar es un trastorno músculo esquelético que afecta la parte baja de la espalda, considerado como un problema de salud pública y catalogado como un desastre en el sitio de trabajo, se encuentra en las 10 primeras causas de enfermedad profesional reportadas por las entidades prestadoras de servicios de salud, generando ausentismo y discapacidad laboral en los países industrializados, con costos que oscilan de los 20 mil a los 98 millones de dólares en los Estados Unidos. Objetivo Determinar la prevalencia de patologías lumbares calificadas y sus factores ocupacionales asociados en una entidad promotora de salud de Bogotá Colombia durante 2013 al 2014. Metodología Se realizó un estudio de corte transversal con datos secundarios pertenecientes a 318 pacientes de una entidad promotora de salud en la ciudad de Bogotá que fueron diagnosticados con patologías lumbares (lumbalgia-lumbago, discopatía lumbar, trastorno de disco intervertebral, espondilolistesis, espondilólisis, hernia discal), y remitidos a medicina laboral o solicitaron calificación de origen en primera oportunidad, en el periodo comprendido entre el año 2013 al 2014. Las variables incluidas fueron sociodemográficas, ocupacionales y diagnósticos médicos, específicamente patologías lumbares. Se realizó distribuciones de frecuencias, medidas de tendencia central y dispersión, análisis de asociación mediante la prueba Chi cuadrado de Pearson y un análisis multivariado a través del modelo de regresión binaria logística y el análisis de concordancia usando el índice de Kappa. Para las pruebas se utilizó un nivel de significación de 0,05. Se digitó y depuró en SPSS versión 23. Resultado El total de usuarios diagnosticados con patologías lumbares fue de 318 de los cuales el 57,2% fueron de sexo masculino con edad promedio de 43 años (D.E 7,9 años). Se encontró asociación significativa entre lumbalgia y movimientos de columna lumbar y levantamiento de carga (p<0,05); discopatía lumbar y movimientos de columna lumbar y factores multicausales (p<0,05); trastorno de disco intervertebral y factores multicausales (p<0.05), hernia de disco y levantamiento de cargas (p<0,05). Respecto a espondilolistesis y espondilólisis no se encontró asociación con ningún factor de riesgo, pero si se encontró asociación significativa entre origen y movimientos de columna lumbar (p= 0.010), con postura mantenida (p= 0.014), con causas multifactoriales (p= 0.000). El grado de concordancia entre la entidad promotora de salud y la administradora de riesgos laborales arrojó un valor en el índice de kappa de 0.432 (p= 0.000) correspondiendo a un grado de acuerdo moderado; para la concordancia entre la entidad promotora de salud y la junta de calificación el índice de kappa fue de 0.680 (p= 0.000) grado de acuerdo alto. Conclusión Las patologías lumbares tienen un alta prevalencia en la población trabajadora como en la no trabajadora, encontrándose un gran número de factores condicionantes a estas enfermedades generando altos costos en días perdidos laborales y en días de incapacidad: Por lo tanto, es importante determinar si estas son catalogadas de origen común o de origen laboral, para establecer programas de vigilancia epidemiológica y programas preventivos.

Gene expression and genome-wide association studies analysis to select heavy pigs for protected designation of origin cured meats production

The high quality of protected designation of origin (PDO) dry-cured pork products depends largely on the chemical and physical parameters of the fresh meat and their variation during the production process of the final product. The discovery of the mechanisms that regulate the variability of these parameters was aided by the reference genome of swine adjuvant to genetic analysis methods. This thesis can contribute to the discovery of genetic mechanisms that regulate the variability of some quality parameters of fresh meat for PDO dry-cured pork production. The first study is of gene expression and showed that between low and high glycolytic potential (GP) samples of Semimembranosus muscle of Italian Large White (ILW) pigs in early postmortem, the differentially expressed genes were all but one over expressed in low GP. These were involved in ATP biosynthesis processes, calcium homeostasis, and lipid metabolism including the potential master regulator gene Peroxisome Proliferator-Activated Receptor Alpha (PPARA). The second is a study in commercial hybrid pigs to evaluate correlations between carcass and fresh ham traits, including carcass and fresh ham lean meat percentages, the former, a potential predictor of the latter. In addition, a genome-wide association study allowed the identification of chromosome-wide associations with phenotypic traits for 19 SNPs, and genome-wide associations for 14 SNPs for ferrochelatase activity. The latter could be a determinant for color variation in nitrite-free dry-cured ham. The third study showed gene expression differences in the Longissimus thoracis muscle of ILW pigs by feeding diets with extruded linseed (source of polyunsaturated fatty acids) and vitamin E and selenium (diet three) or natural (diet four) antioxidants. The diet three promoted a more rapid and massive immune system response possibly determined by improvement in muscle tissue function, while the diet four promoted oxidative stability and increased the anti-inflammatory potential of muscle tissue.

O papel da propriocepção no desenvolvimento da força muscular e da flexibilidade

Universidade Estadual de Campinas . Faculdade de Educação Física

Treinamento de força e suplementação de creatina : a densidade da carga como estimulo otimizador nos ajustes morfologicos e funcionais

Universidade Estadual de Campinas . Faculdade de Educação Física

Avaliação isocinetica de joelho em jogadores de futebol categoria sub-20

Universidade Estadual de Campinas . Faculdade de Educação Física

Avaliação de um programa de treinamento da flexibilidade utilizado para compensação de esforços

Universidade Estadual de Campinas . Faculdade de Educação Física

Angioleiomioma de cavidade nasal: relato de um caso e revisão de literatura

Leiomioma de cavidade nasal e seios paranasais é raro. Ele constitui menos de 1% de todos os leiomiomas do corpo humano. Isto se deve à escassez de células musculares no nariz. Estas neoplasias podem ser classificadas em três grupos: leiomioma, angiomioma e leiomioma epitelióide. Somente 15 casos de angiomioma foram encontrados na literatura. O tratamento de escolha é a excisão cirúrgica. Um novo caso e a revisão da literatura são apresentados.