NIH R21NS42516 para TGH Craig H Nielsen Foundation Grant 83.860 para TGH NIDRR-RRTC. APTA Bolsa de Doutorado para CKT

<ol>
	<li>Miller, J. F., Paul, K. D., Rymer, W. Z., Heckman, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=5-HT1B/1D+agonist+CGS-12066B+attenuates+clasp+knife+reflex+in+the+cat.">5-HT1B/1D agonist CGS-12066B attenuates clasp knife reflex in the cat.</a> J Neurophysiol. 74, 453-456 (1995).</li><li>Gimenez y Ribotta, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinematic+analysis+of+recovered+locomotor+movements+of+the+hindlimbs+in+paraplegic+rats+transplanted+with+monoaminergic+embryonic+neurons.">Kinematic analysis of recovered locomotor movements of the hindlimbs in paraplegic rats transplanted with monoaminergic embryonic neurons.</a> Ann N Y Acad Sci. 860, 521-523 (1998).</li><li>Landry, E. S., Guertin, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+effects+of+5-HT1+and+5-HT2+receptor+agonists+on+hindlimb+movements+in+paraplegic+mice.">Differential effects of 5-HT1 and 5-HT2 receptor agonists on hindlimb movements in paraplegic mice.</a> Prog Neuropsychopharmacol Biol Psychiatry. 28, 1053-1060 (2004).</li><li>Liu, J., Jordan, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stimulation+of+the+parapyramidal+region+of+the+neonatal+rat+brain+stem+produces+locomotor-like+activity+involving+spinal+5-HT7+and+5-HT2A+receptors.">Stimulation of the parapyramidal region of the neonatal rat brain stem produces locomotor-like activity involving spinal 5-HT7 and 5-HT2A receptors.</a> J Neurophysiol. 94, 1392-1404 (2005).</li><li>Fong, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spinal+cord-transected+mice+learn+to+step+in+response+to+quipazine+treatment+and+robotic+training.">Spinal cord-transected mice learn to step in response to quipazine treatment and robotic training.</a> J Neurosci. 25, 11738-11747 (2005).</li><li>Murray, K., Nakae, A., Stephens, M. J., Rank, M., D Amico, J., Harvey, P., Li, X., Harris, L., Ballou, E. W., Anelli, R., Heckman, C. J., Mashimo, T., Vavrek, R., Sanelli, L., Gorassini, M. A., Bennett, D. J., Fouad, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+motoneuron+and+locomotor+function+after+chronic+spinal+cord+injury+depends+on+constitutive+activity+in+5-HT2C+receptors.">Recovery of motoneuron and locomotor function after chronic spinal cord injury depends on constitutive activity in 5-HT2C receptors.</a> Nature Medicine. , (2010).</li><li>Pariente, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluoxetine+modulates+motor+performance+and+cerebral+activation+of+patients+recovering+from+stroke.">Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke.</a> Ann Neurol. 50, 718-729 (2001).</li><li>Hornby, T. G., Lewek, M. D., Thompson, C. K., Heitz, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeated+maximal+volitional+effort+contractions+in+human+spinal+cord+injury:+initial+torque+increases+and+reduced+fatigue.">Repeated maximal volitional effort contractions in human spinal cord injury: initial torque increases and reduced fatigue.</a> Neurorehabil Neural Repair. 23, 928-938 (2009).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> ACSM's Guidelines for Exercise Testing and Prescription. , (2000).</li><li>Lewek, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Allowing+intralimb+kinematic+variability+during+locomotor+training+poststroke+improves+kinematic+consistency:+a+subgroup+analysis+from+a+randomized+clinical+trial.">Allowing intralimb kinematic variability during locomotor training poststroke improves kinematic consistency: a subgroup analysis from a randomized clinical trial.</a> Phys Ther. 89, 829-839 (2009).</li><li>Fung, J., Barbeau, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+dynamic+EMG+profile+index+to+quantify+muscular+activation+disorder+in+spastic+paretic+gait.">A dynamic EMG profile index to quantify muscular activation disorder in spastic paretic gait.</a> Electroencephalogr Clin Neurophysiol. 73, 233-244 (1989).</li><li>Bohannon, R. W., Smith, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interrater+reliability+of+a+modified+Ashworth+scale+of+muscle+spasticity.">Interrater reliability of a modified Ashworth scale of muscle spasticity.</a> Phys Ther. 67, 206-207 (1987).</li><li>Benz, E., TG, H. o. r. n. b. y., RK, B. o. d. e., Scheidt, R. A., Schmit, B. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+physiologically+based+clinical+measure+for+spastic+reflexes+in+spinal+cord+injury.">A physiologically based clinical measure for spastic reflexes in spinal cord injury.</a> Arch Phys Med Rehabil. 86, 52-59 (2005).</li></ol>

Não há conflitos de interesse declarados.

Esta demonstração vídeo destaca métodos para avaliar mudanças na atividade reflexa, força volitiva e deambulação após a administração oral aguda de ISRSs em humanos SCI. Esta bateria de avaliações demonstra que apesar dos aumentos nos chamados atividade anormal do reflexo após a administração oral aguda de um SSRI, o indivíduo com SCI demonstraram melhorias na força volitiva, com apenas pequenas alterações na capacidade de locomoção. Nesses indivíduos os efeitos da espasticidade aumentada não aparecem prejudicial à função ambulatorial. Além disso melhorias na capacidade de caminhar pode ser mais pronunciado em indivíduos com lesões agudas. Estudos do uso continuado dessas avaliações semelhantes quantitativa e clínica para determinar a eficácia da combinação SSRIs e intensivo intervenções físicas, como tem sido empregada em modelos animais de SCI. Com uma estrutura sólida teórica baseada em pesquisas científicas de longa data e relativamente novo básico, esses métodos podem ajudar a traduzir tais informações para uma população clínica e podem desafiar alguns dos protocolos tradicionais utilizados na prática clínica para aumentar a recuperação funcional em indivíduos com SCI.

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<td>Isokinetic Dynamometer</td>
<td>&nbsp;</td>
<td>Biodex</td>
<td>System 3 with Rehab Toolkit</td>
<td>&nbsp;</td>
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<td>EMG system</td>
<td>&nbsp;</td>
<td>Delysis</td>
<td>Bagnoli 2.1</td>
<td>&nbsp;</td>
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<td>EMG system</td>
<td>&nbsp;</td>
<td>Noraxon</td>
<td>Mayosystem 1400a</td>
<td>&nbsp;</td>
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<td>Metabolic</td>
<td>&nbsp;</td>
<td>ConMed</td>
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<td>Bertec</td>
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<td>&nbsp;</td>
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methods to quantify pharmacologically induced alterations in motor function in human incomplete sci

Lesão da medula espinal (SCI) é uma doença debilitante, que produz déficits profundos no controle motor da vontade. Após a estabilização médica, a recuperação da SCI tipicamente envolve a reabilitação a longo prazo. Enquanto a recuperação da capacidade de caminhar é a meta principal em muitos pacientes iniciais após a lesão, aqueles com um SCI motor incompleto, indicando preservação parcial do controle volitivo, pode ter o suficiente residual vias descendentes necessário para alcançar este objetivo. No entanto, apesar de intervenções físicas, deficiências motoras, incluindo fraqueza, ea manifestação da atividade involuntária de reflexo anormal, chamada de espasticidade ou espasmos, são pensados ​​para contribuir para a recuperação andando reduzida. Pensamento doutrinário sugere que a remediação deste reflexos motores anormais associados com SCI irá produzir benefícios funcionais para o paciente. Por exemplo, médicos e terapeutas irá fornecer as intervenções farmacológicas específicas ou físicas voltadas para a redução da espasticidade ou espasmos, embora continua a haver poucos dados empíricos que sugerem que estas estratégias melhorar a capacidade de andar. Na últimas décadas, acumulando dados sugeriu que os agentes neuromoduladores específicos, incluindo agentes que imitam ou facilitar as ações do monoaminas, incluindo a serotonina (5HT) e norepinefrina (NE), pode iniciar ou aumentar a pé comportamentos em modelos animais de SCI. Curiosamente, muitos destes agentes, particularmente agonistas 5HTergic, podem aumentar a excitabilidade espinal, que por sua vez também aumenta a atividade reflexa nestes animais. Contra-intuitivo para as teorias tradicionais de recuperação após humana SCI, a evidência empírica a partir de experimentos de ciência básica sugerem que essa hiper-excitabilidade reflexa e geração de comportamentos locomotores são conduzidos em paralelo por entradas neuromoduladores (5HT) e pode ser necessário para a recuperação funcional após uma lesão medular. A aplicação deste novo conceito derivado de estudos científicos básicos para promover a recuperação seguintes SCI humana parece ser perfeita, apesar de a tradução directa dos resultados pode ser extremamente desafiador. Especificamente, nos modelos animal, um cateter implantado facilita a entrega de muito específicos compostos agonista 5HT diretamente sobre o circuito da coluna vertebral. A tradução desta técnica para o homem é dificultada pela falta de técnicas cirúrgicas específicas ou disponíveis agentes farmacológicos direcionados para subtipos de receptores 5HT que são seguros e eficazes para ensaios clínicos humanos. No entanto, a administração oral de agentes comumente disponíveis 5HTergic, tais como inibidores seletivos da recaptação da serotonina (SSRIs), pode ser uma opção viável para aumentar a concentração de 5HT centrais para facilitar a caminhada de recuperação em seres humanos. Quantificação sistemática de como esses ISRS modular comportamentos motor humano após uma lesão medular, com um foco específico sobre a força, reflexos, ea recuperação da capacidade de andar, estão faltando. Esta demonstração de vídeo é uma tentativa sistemática e progressiva para avaliar quantitativamente a modulação da atividade reflexa, força volitiva e deambulação após a administração oral aguda de um SSRI no SCI humana. Agentes são aplicadas em dias única para avaliar os efeitos imediatos sobre a função do motor nesta população de pacientes, com estudos de longo prazo envolvendo a administração da droga combinada com repetidas intervenções físicas intensas.

Watch this Scientific Journal Video about Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI at JoVE.com

Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

Este vídeo demonstra modulação da atividade reflexa, força volitiva e deambulação através de avaliação clínica e quantitativa em indivíduos com motor SCI incompleta como resultado da administração oral aguda de um inibidor da recaptação da serotonina (ISRS).

Os métodos para quantificar alterações farmacologicamente induzida na função motora em humanos SCI incompleta

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, ...

methods-to-quantify-pharmacologically-induced-alterations-motor

Research

JoVE Journal

Medicine

13.6K visualizações.  Rehabilitation Institute of Chicago. Este vídeo demonstra modulação da atividade reflexa, força volitiva e deambulação através de avaliação clínica e quantitativa em indivíduos com motor SCI incompleta como resultado da administração oral aguda de um inibidor da recaptação da serotonina (ISRS).

Vídeo: Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

Technique to Collect Fungiform (Taste) Papillae from Human Tongue

The sense of taste is critical for human life. It informs the body about the quality of food that will be potentially ingested and stimulates metabolic processes that prepare the alimentary canal for digestion. Steady progress is being made towards understanding the early biochemical and molecular events underlying taste transduction (for a review, Breslin and Spector, 20081). However, progress to date has largely resulted from animal models. Yet, since marked differences in receptor specificity and receptor density vary among species, human taste transduction will only be understood by using human taste tissue. Here we describe a biopsy technique to collect human fungiform papillae, visible as rounded pink anterior structures, about 0.5 mm in diameter that contain taste buds. These biopsied papillae are used for several purposes including the isolation of viable taste bud cells, in situ hybridization, immunohistochemistry and, through techniques of molecular biology, the identification of taste-specific novel proteins.

Technique to Collect Fungiform Taste Papillae from Human Tongue

Knowledge of molecular mechanisms underlying gustatory transduction has recently enjoyed significant advances, largely due to using animal models. However, the wide diversity in taste sensitivity and specificity among mammals warrants studies in human tissue. We describe a biopsy technique to collect living taste cells from the papillae on human tongue.

Técnica para coletar fungiformes (Taste) papilas da língua humana

The sense of taste is critical for human life. It informs the body about the quality of food that will be potentially ingested and stimulates metabolic ...

Medicina

In Vivo Canine Muscle Function Assay

We describe a minimally-invasive and reproducible method to measure canine pelvic limb muscle strength and muscle response to repeated eccentric 
contractions. The pelvic limb of an anesthetized dog is immobilized in a stereotactic frame to align the tibia at a right angle to the femur. Adhesive wrap affixes the 
paw to a pedal mounted on the shaft of a servomotor to measure torque. Percutaneous nerve stimulation activates pelvic limb muscles of the paw to either push (extend) or 
pull (flex) against the pedal to generate isometric torque. Percutaneous tibial nerve stimulation activates tibiotarsal extensor muscles. Repeated eccentric (lengthening) 
contractions are induced in the tibiotarsal flexor muscles by percutaneous peroneal nerve stimulation. The eccentric protocol consists of an initial isometric contraction 
followed by a forced stretch imposed by the servomotor. The rotation effectively lengthens the muscle while it contracts, e.g., an eccentric contraction. During 
stimulation flexor muscles are subjected to an 800 msec isometric and 200 msec eccentric contraction. This procedure is repeated every 5 sec. To avoid fatigue, 4 min rest 
follows every 10 contractions with a total of 30 contractions performed.

In Vivo Canine Muscle Function Assay

We describe a minimally-invasive and painless method to measure canine hindlimb muscle strength and muscle response to repeated eccentric contractions.

Em função Assay Canine Muscle Vivo

We describe a minimally-invasive and reproducible method to measure canine pelvic limb muscle strength and muscle response to repeated eccentric 
...

Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily obtained electrocardiogram (ECG) are established, well-validated prognostic indicators of cardiac risk in patients suffering 
from a number of cardiomyopathies. Increased heart rate, decreased heart rate variability (HRV), and increased duration and variability of cardiac 
ventricular electrical activity (QT interval) are all indicative of enhanced cardiac risk 1-4. In animal models, it is valuable to compare 
these ECG-derived variables and susceptibility to experimentally induced arrhythmias. Intravenous infusion of the arrhythmogenic agent aconitine has
 been widely used to evaluate susceptibility to arrhythmias in a range of experimental conditions, including animal models of depression 5 and 
 hypertension 6, following exercise 7 and exposure to air pollutants 8, as well as determination of the antiarrhythmic efficacy of pharmacological 
 agents 9,10. 
It should be noted that QT dispersion in humans is a measure of QT interval variation across the full set of leads from a 
standard 12-lead ECG. Consequently, the measure of QT dispersion from the 2-lead ECG in the rat described in this protocol is different than that 
calculated from human ECG records. This represents a limitation in the translation of the data obtained from rodents to human clinical medicine.
Status epilepticus (SE) is a single seizure or series of continuously recurring seizures lasting more than 30 min 
11,12 11,12, and results in mortality in 20% of cases 13. Many individuals survive the SE, but die within 30 days 14,15.
 The mechanism(s) of this delayed mortality is not fully understood. It has been suggested that lethal ventricular arrhythmias contribute to many of these 
 deaths 14-17. In addition to SE, patients experiencing spontaneously recurring seizures, i.e. epilepsy, are at risk of premature 
 sudden and unexpected death associated with epilepsy (SUDEP) 18. As with SE, the precise mechanisms mediating SUDEP are not known. 
 It has been proposed that ventricular abnormalities and resulting arrhythmias make a significant contribution 18-22.
 To investigate the mechanisms of seizure-related cardiac death, and the efficacy of cardioprotective therapies, it is 
 necessary to obtain both ECG-derived indicators of risk and evaluate susceptibility to cardiac arrhythmias in animal models of seizure disorders 
 23-25. Here we describe methods for implanting ECG electrodes in the Sprague-Dawley laboratory rat (Rattus norvegicus), following SE,
 collection and analysis of ECG recordings, and induction of arrhythmias during iv infusion of aconitine.
 These procedures can be used to directly determine the relationships between ECG-derived measures of cardiac electrical 
 activity and susceptibility to ventricular arrhythmias in rat models of seizure disorders, or any pathology associated with increased risk of sudden 
 cardiac death.

Techniques for measurement of electrical activity of the heart by electrocardiogram (ECG), and analysis of cardiac risk factors and susceptibility to arrhythmias following status epilepticus (SE) in the rat are described.

Métodos para ECG Avaliação de Indicadores de risco cardíaco e Susceptibilidade à Aconitina arritmias induzidas em ratos após a Estado Epiléptico

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily ...

Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to assess changes in myelination at the central nervous system (CNS). However, standard measurements, including routine visual tests and MRI scans, are not sensitive enough for this purpose. We present two visual tests addressing dynamic monocular and binocular functions which may closely associate with the extent of myelination along visual pathways. These include Object From Motion (OFM) extraction and Time-constrained stereo protocols. In the OFM test, an array of dots compose an object, by moving the dots within the image rightward while moving the dots outside the image leftward or vice versa. The dot pattern generates a camouflaged object that cannot be detected when the dots are stationary or moving as a whole. Importantly, object recognition is critically dependent on motion perception. In the Time-constrained Stereo protocol, spatially disparate images are presented for a limited length of time, challenging binocular 3-dimensional integration in time. Both tests are appropriate for clinical usage and provide a simple, yet powerful, way to identify and quantify processes of demyelination and remyelination along visual pathways. These protocols may be efficient to diagnose and follow optic neuritis and multiple sclerosis patients.
In the diagnostic process, these protocols may reveal visual deficits that cannot be identified via current standard visual measurements. Moreover, these protocols sensitively identify the basis of the currently unexplained continued visual complaints of patients following recovery of visual acuity. In the longitudinal follow up course, the protocols can be used as a sensitive marker of demyelinating and remyelinating processes along time. These protocols may therefore be used to evaluate the efficacy of current and evolving therapeutic strategies, targeting myelination of the CNS.

Object From Motion (OFM) and Time-constrained stereo protocols are sensitive tools to identify monocular and binocular dynamic visual function deficits, which are uniquely affected in optic neuritis patients. Furthermore, these tests may be used as quantitative noninvasive tools to assess the extent of myelination along visual pathways.

Testes dinâmicos visuais para identificar e quantificar danos Visual e Reparação Após desmielinização na neurite óptica Pacientes

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to ...

Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research. Successful outcomes are dependent upon three critical components: test chambers that permit self-feeding while standing unrestrained in a confined space, recipes that mask the aversive taste/odor of commercially-available oral contrast agents, and a step-by-step test protocol that permits quantification of swallow physiology. Elimination of one or more of these components will have a detrimental impact on the study results. Moreover, the energy level capability of the fluoroscopy system will determine which swallow parameters can be investigated. Most research centers have high energy fluoroscopes designed for use with people and larger animals, which results in exceptionally poor image quality when testing mice and other small rodents. Despite this limitation, we have identified seven VFSS parameters that are consistently quantifiable in mice when using a high energy fluoroscope in combination with the new murine VFSS protocol. We recently obtained a low energy fluoroscopy system with exceptionally high imaging resolution and magnification capabilities that was designed for use with mice and other small rodents. Preliminary work using this new system, in combination with the new murine VFSS protocol, has identified 13 swallow parameters that are consistently quantifiable in mice, which is nearly double the number obtained using conventional (i.e., high energy) fluoroscopes. Identification of additional swallow parameters is expected as we optimize the capabilities of this new system. Results thus far demonstrate the utility of using a low energy fluoroscopy system to detect and quantify subtle changes in swallow physiology that may otherwise be overlooked when using high energy fluoroscopes to investigate murine disease models.

This study successfully adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research.

Adaptação Humanos videofluoroscópicos Andorinha Métodos de Estudo de detectar e caracterizar Disfagia em modelos de doenças Murino

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating ...

Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most reliable assessments regarding therapeutic efficacy. We present clinical and radiological outcome measures used in ambulatory patients participating in our trial &#34;Treatment with L-citrulline and metformin in Duchenne muscular dystrophy&#34;. The motor function measure is a validated test in patients with neuromuscular disorders that consists of 32 items and assesses all three dimensions of motor performance including standing and transfer (D1 subscore), axial and proximal motor function (D2 subscore), and distal motor function (D3 subscore). The test shows high intra- and inter-rater variability but only when strictly following guidelines of the materials, examination steps, and calculation of scores. The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration. Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability.

The aim of this study is to present the most reliable clinical outcome measures and their correlations with quantitative muscle MRI in ambulant patients with Duchenne muscular dystrophy.

Medições da função motora e outros parâmetros de resultados clínicos em Ambulant crianças com Distrofia Muscular de Duchenne

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most ...

A Non-Invasive Method for Generating the Cyclic Loading-Induced Intra-Articular Cartilage Lesion Model of the Rat Knee

The pathophysiology of primary osteoarthritis (OA) remains unclear. However, a specific subclassification of OA in relatively younger age groups is likely correlated with a history of articular cartilage damage and ligament avulsion. Surgical animal models of OA of the knee play an important role in understanding the onset and progression of post-traumatic OA and aid in the development of novel therapies for this disease. However, non-surgical models have been recently considered to avoid traumatic inflammation that could affect the evaluation of the intervention. 
In this study, an intra-articular cartilage lesion rat model induced by in vivo cyclic compressive loading was developed, which allowed researchers to (1) determine the optimal magnitude, speed, and duration of load that could cause focal cartilage damage; (2) assess post-traumatic spatiotemporal pathological changes in chondrocyte vitality; and (3) evaluate the histological expression of destructive or protective molecules that are involved in the adaptation and repair mechanisms against joint compressive loads. This report describes the experimental protocol for this novel cartilage lesion in a rat model.

Here, we present the cyclic loading-induced intra-articular cartilage lesion model of the rat knee, generated by 60 cyclic compressions over 20 N, resulting in damage to the femoral condylar cartilage in rats.

Um Método Não Invasivo para Gerar o Modelo de Lesão da Cartilagem Intra-Articular Induzida por Carga Cíclica do Joelho de Rato

The pathophysiology of primary osteoarthritis (OA) remains unclear. However, a specific subclassification of OA in relatively younger age groups is likely ...

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion

The benefits of renal sympathetic denervation (RDN) on blood pressure have been proved in a large number of clinical trials in recent years. However, the regulatory mechanism of RDN on hypertension remains elusive. Thus, it&#39;s essential to establish a simpler RDN model in mice. In this study, osmotic mini pumps filled with Angiotensin II were implanted in 14-week-old C57BL/6 mice. One week after the implantation of the mini-osmotic pump, a modified RDN procedure was performed on bilateral renal arteries of the mice using phenol. Age-sex-matched mice were given saline and served as sham group. Blood pressure was measured at baseline and every week subsequently for 21 days. Then, renal artery, abdominal aorta and heart were collected for histological examination using H&#38;E and Masson staining. In this study, we present a simple, practical, repeatable, and standardized RDN model, which can control hypertension and alleviate cardiac hypertrophy. The technique can denervate peripheral renal sympathetic nerves without renal artery damage. Compared to previous models, the modified RDN facilitates the study of the pathobiology and pathophysiology of hypertension.

Here, we present a protocol for renal sympathetic denervation (RDN) in mice with hypertension induced by Angiotensin II infusion. The procedure is repeatable, convenient and allows to study the regulatory mechanisms of RDN on hypertension and cardiac hypertrophy.

Denervação renal melhorada Hipertensão Mitigada Induzida por Infusão de Angiotensina II

The benefits of renal sympathetic denervation (RDN) on blood pressure have been proved in a large number of clinical trials in recent years. However, the ...

Determinando a respiração em espermatozóides humanos por respirometria de alta resolução

High-Resolution Respirometry to Assess Mitochondrial Function in Human Spermatozoa

Semen quality is often studied by routine semen analysis, which is descriptive and often inconclusive. Male infertility is associated with altered sperm mitochondrial activity, so the measurement of sperm mitochondrial function is an indicator of sperm quality. High-resolution respirometry is a method of measuring the oxygen consumption of cells or tissues in a closed-chamber system. This technique can be implemented to measure respiration in human sperm and provides information about the quality and integrity of the sperm mitochondria. High-resolution respirometry allows the cells to move freely, which is an a priori advantage in the case of sperm. This technique can be applied with intact or permeabilized spermatozoa and allows for the study of intact sperm mitochondrial function and the activity of individual respiratory chain complexes. The high-resolution oxygraph instrument uses sensors to measure the oxygen concentration coupled with sensitive software to calculate the oxygen consumption. The data are used to calculate respiratory indices based on the oxygen consumption ratios. Consequently, the indices are the proportions of two oxygen consumption rates and are internally normalized to the cell number or protein mass. The respiratory indices are an indicator of sperm mitochondrial function and dysfunction.

Autor em destaque: Avançando na pesquisa de infertilidade masculina, desvendando o metabolismo do esperma e a função mitocondrial 

The analysis of sperm mitochondrial function by high-resolution respirometry permits the measurement of the oxygen consumption of freely moving spermatozoa in a closed-chamber system. The technique can be applied to measure respiration in human spermatozoa, which provides information on sperm mitochondrial characteristics and integrity.

Respirometria de Alta Resolução para Avaliação da Função Mitocondrial em Espermatozoides Humanos

Semen quality is often studied by routine semen analysis, which is descriptive and often inconclusive. Male infertility is associated with altered sperm ...