NIH R21NS42516 zu TGH Craig H Nielsen Foundation Grant 83860 für TGH NIDRR-RRTC. APTA Promotionsstipendium für 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>

Dieses Video-Demonstration zeigt Methoden, um Veränderungen in Reflex-Aktivität, willentliche Kraft und Gehfähigkeit nach der akuten oralen Verabreichung von SSRIs in der menschlichen SCI zu beurteilen. Diese Batterie von Assessments zeigt, dass trotz des Anstiegs der sogenannten abnormen Reflex-Aktivität nach einer akuten oralen Verabreichung eines SSRI, das Individuum mit SCI Verbesserungen in willentliche Stärke demonstriert, mit nur geringfügigen Änderungen in der Bewegungsorgane Fähigkeit. Bei diesen Personen die Auswirkungen von Augmented Spastik nicht angezeigt nachteilig auf ambulante Funktion. Darüber hinaus Verbesserungen in der Gehfähigkeit noch ausgeprägter sein bei Personen mit akuten Läsionen. Fortsetzung des Studiums mit diesen ähnliche quantitative und klinischen Beurteilung der Wirksamkeit von kombinierten SSRIs und intensive körperliche Interventionen zu bestimmen, wie es in Tiermodellen von SCI eingesetzt. Mit einer soliden theoretischen Rahmen auf langjährige und relativ neu die Grundlagenforschung basiert, können diese Methoden zu übersetzen diese Informationen an einer klinischen Bevölkerung zu helfen und kann einige der traditionellen Protokollen in der klinischen Praxis verwendet werden, um die funktionelle Erholung bei Patienten mit SCI erweitern Herausforderung.

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methods to quantify pharmacologically induced alterations in motor function in human incomplete sci

Rückenmarksverletzung (SCI) ist eine schwächende Krankheit, die tiefe Defizite produziert in willentlichen Motorsteuerung. Nach medizinischen Stabilisierung, Erholung von SCI umfasst in der Regel langfristige Rehabilitation. Während Wiederherstellung der Gehfähigkeit ist ein vorrangiges Ziel bei vielen Patienten bereits nach einer Verletzung, die mit einem Motor unvollständige SCI, was darauf hinweist teilweisen Erhaltung der willentlichen Kontrolle, kann die ausreichende Rest-absteigende Bahnen notwendig, um dieses Ziel zu erreichen. Doch trotz körperlicher Eingriffe sind motorischen Beeinträchtigungen wie Schwäche, und die Manifestation der unwillkürliche Reflex-Aktivität, genannt Spastik oder Spasmen, dachte zu reduzieren Fuß Erholung beitragen. Doktrinären Denken lässt vermuten, dass die Sanierung von dieser abnormalen motorischen Reflexe mit SCI verbunden werden funktionelle Vorteile für den Patienten zu erzeugen. Zum Beispiel werden Ärzte und Therapeuten bieten spezifische pharmakologische oder physikalische Eingriffe zur Verringerung der Spastik oder Spasmen gerichtet, obwohl es nach wie vor wenig empirische Daten darauf hindeutet, dass diese Strategien Gehfähigkeit zu verbessern. In den letzten Jahrzehnten hat anfallenden Daten vorgeschlagen, dass bestimmte neuromodulatorischen Agenten, darunter Mittel, die nachahmen oder erleichtern die Aktionen der Monoamine, wie Serotonin (5HT) und Noradrenalin (NE), kann initiieren oder zu erweitern Fuß Verhalten in Tiermodellen der SCI. Interessanterweise können viele dieser Substanzen, insbesondere 5HTergic Agonisten, deutlich erhöhen spinalen Erregbarkeit, die wiederum erhöht auch die Reflex-Aktivität bei diesen Tieren. Counterintuitive zu den traditionellen Theorien der Erholung nach menschlichen SCI, die empirische Evidenz aus der Grundlagenforschung Experimente deuten darauf hin, dass dieser Reflex hyper Erregbarkeit und Generierung von Bewegungs-Verhalten in parallel durch neuromodulatorischen Eingänge (5HT) angetrieben und kann notwendig sein, für die funktionelle Erholung nach SCI. Die Anwendung dieser neuartigen Konzept von grundlegenden wissenschaftlichen Studien abgeleitet, um Erholung nach menschlichen SCI fördern scheint nahtlos, obwohl die direkte Übersetzung der Erkenntnisse kann extrem herausfordernd. Insbesondere in den Tiermodellen, erleichtert einen implantierten Katheter Lieferung von sehr spezifischen 5HT-Agonisten Verbindungen direkt auf die Wirbelsäule Schaltung. Die Übersetzung dieser Technik für den Menschen ist durch den Mangel an bestimmten chirurgischen Techniken oder zur Verfügung pharmakologische Wirkstoffe in Richtung 5HT-Rezeptor-Subtypen, die sicher und wirksam für klinische Studien am Menschen gerichtet sind behindert. Allerdings kann die orale Verabreichung von allgemein verfügbaren 5HTergic Mittel, wie selektive Serotonin-Wiederaufnahmehemmer (SSRIs), ein gangbarer Weg, um zentrale 5HT-Konzentrationen zu erhöhen, um zu erleichtern Walking Erholung beim Menschen. Systematische Quantifizierung, wie diese SSRIs modulieren menschlichen motorischen Verhaltensweisen folgenden SCI, mit einem besonderen Schwerpunkt auf Kraft, Reflexe, und die Wiederherstellung der Gehfähigkeit, fehlen. Dieses Video-Demonstration ist eine fortschreitende Versuch, systematisch und quantitativ zu erfassen die Modulation der Reflex-Aktivität, willentliche Kraft und Gehfähigkeit nach der akuten oralen Verabreichung eines SSRI in der menschlichen SCI. Agenten sind auf einzelne Tage angewendet, um die unmittelbaren Auswirkungen auf die motorischen Funktionen bei dieser Patientengruppe mit Langzeitstudien mit wiederholter Medikamentengabe mit intensiver körperlicher Eingriffe kombiniert beurteilen.

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

Dieses Video zeigt Modulation der Reflex-Aktivität, willentliche Kraft und Gehfähigkeit durch klinische und quantitative Beurteilung bei Personen mit motorischen unvollständige SCI als Folge der akuten oralen Verabreichung eines Serotonin-Wiederaufnahmehemmer (SSRI).

Methoden zur pharmakologisch induzierten Veränderungen der motorischen Funktion in Human Unvollständige SCI Quantify

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 Aufrufe.  Rehabilitation Institute of Chicago. Dieses Video zeigt Modulation der Reflex-Aktivität, willentliche Kraft und Gehfähigkeit durch klinische und quantitative Beurteilung bei Personen mit motorischen unvollständige SCI als Folge der akuten oralen Verabreichung eines Serotonin-Wiederaufnahmehemmer (SSRI).

Serie: 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.

Technik zu pilzförmigen (Taste) Papillen aus menschlichen Zunge sammeln

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 ...

Forschung

Medizin

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.

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.

Methoden zur EKG-Auswertung der Indikatoren des Cardiac Risk, und die Anfälligkeit für Aconitin-induzierten Arrhythmien in Ratten nach Status epilepticus

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.

Dynamische Visuelle Tests zur Identifizierung und Quantifizierung von Visual Schäden und Reparaturen Nach Demyelinisierung in Optikusneuritis Patienten

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.

Anpassung Menschen Videofluoroscopic Swallow Studienmethoden nachgewiesen und charakterisiert Dysphagie in Murine Krankheitsmodelle

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.

Messungen der motorischen Funktion und anderen klinischen Outcome-Parameter bei ambulanten Kindern mit Duchenne-Muskeldystrophie

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.

Eine nicht-invasive Methode zur Erzeugung des zyklischen Belastungsinduzierten intraartikulären Knorpelläsionsmodells des Rattenknies

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.

Verbesserte renale Denervierung milderte Hypertonie durch 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 ...

Bestimmung der Atmung in menschlichen Spermien durch hochauflösende Respirometrie

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 im Rampenlicht: Förderung der Forschung zur männlichen Unfruchtbarkeit durch Entschlüsselung des Spermienstoffwechsels und der mitochondrialen Funktion 

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.

Hochauflösende Respirometrie zur Beurteilung der Mitochondrienfunktion in menschlichen Spermien

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