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  • 1
    Electronic Resource
    Electronic Resource
    Chronic Mitochondrial Inhibition Induces Selective Motoneuron Death In Vitro: A New Model for Amyotrophic Lateral Sclerosis (2000)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 74 (2000), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Evidence is increasing that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis, a neurodegenerative disease characterized by selective motoneuron death. To study the role of mitochondrial dysfunction in the pathways leading to motoneuron death, we developed an in vitro model of chronic motoneuron toxicity, based on malonate-induced inhibition of complex II in the mitochondrial electron transport chain. Treatment with malonate resulted in a dose-dependent decrease in cellular ATP levels. We observed that motoneurons were significantly more vulnerable to mitochondrial inhibition than control neurons in the dorsal horn. We could reproduce this dose-dependent phenomenon with the complex IV inhibitor sodium azide. The free radical scavenger α-phenyl-N-tert-butylnitrone, the AMPA/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione, and riluzole, a drug that is currently used for the treatment of amyotrophic lateral sclerosis, were protective against malonate-induced motoneuron death. Furthermore, the caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and z-Asp-Glu-Val-Asp-fluoromethyl ketone were both protective against malonate toxicity. Our model shows that chronic mitochondrial inhibition leads to selective motoneuron death, which is most likely apoptotic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2000.741158.x
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  • 2
    Electronic Resource
    Electronic Resource
    Mechanisms underlying in vivo neuroprotection by the endocannabinoid anandamide and the cannabinoid/vanilloid receptor agonist, arvanil (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The endocannabinoid anandamide (AEA) and some of its oxidative metabolites are putative ligands for the vanilloid receptor (VR1). AEA affords protection against excitotoxicity induced in vivo by ouabain, a Na+/K+-ATPase inhibitor. This effect is only partly dependent of the cannabinoid CB1 receptor. Here, we assessed whether VR1 is involved in neuroprotection by AEA and arvanil, which is a hydrolysis-stable ligand for both VR1 and CB1. Using magnetic resonance imaging we show that: (i) modulation of VR1, by the agonists arvanil and capsaicin and the antagonist capsazepine, leads to neuroprotective effects in the late but not acute phase after i.c. ouabain-injection; (ii) arvanil is a potent neuroprotectant, acting at both CB1 and VR1; and (iii) the neuroprotective effects of AEA are mediated by CB1 but not by lipoxygenase metabolites or VR1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.85.s2.6_1.x
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  • 3
    Electronic Resource
    Electronic Resource
    Neuroprotective Effects of Radical Scavengers in an Intact Dorsal Root Ganglion Hypoxia Model (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 765 (1995), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1995.tb16566.x
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  • 4
    Electronic Resource
    Electronic Resource
    Creatine kinase isoenzyme profiles after exercise in the rat: sex-linked differences in leakage of CK-MM (1988)
    Springer
    Pflügers Archiv 412 (1988), S. 417-421 
    Details
    ISSN: 1432-2013
    Keywords: Exercise ; Creatine kinase isoenzymes ; Aspartate aminotransferase ; Sex difference ; Muscle damage ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in creatine kinase (CK) activity and CK isoenzyme profiles in plasma after exercise were studied in rats in order to establish the source of the exercise-induced rise in CK activity. Male and female rats ran on a treadmill for 2 h and blood samples, taken before and after exercise, were assayed for total CK, CK isoenzymes and aminoaspartate transaminase (AST) activity. These enzymes were also assayed in homogenates of liver and several muscles. We found that the isoenzyme composition of liver, plasma and muscle did not differ between the sexes. However, the exercise-induced CK and AST responses did differ: CK and AST increased after exercise in males (101% and 15% resp.), but much less in females (47% and 1%). Although the isoenzyme profiles in rest did not differ, significant differences were observed after running: in males CK-MM inereased with 678%, but females only showed a 114% increase. In contrast, CK-BB showed a small increase that was about the same for both sexes (males 41%, females 35%). We conclude that both males and females show a small and similar increase in CK-BB activity after exercise, and that a large release of CK-MM from skeletal muscle, observed only in males, accounts for sex-linked differences reported earlier.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01907561
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  • 5
    Electronic Resource
    Electronic Resource
    Prednisone can protect against exercise-induced muscle damage (1996)
    Springer
    Journal of neurology 243 (1996), S. 410-416 
    Details
    ISSN: 1432-1459
    Keywords: Prednisone ; Exercise Muscle damage ; Dystrophin ; Creatine kinase activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an experimental animal exercise model we tested whether daily administration of prednisone prevents the development of mechanically induced muscle fibre damage. Six-week-old rats were treated with different doses of prednisone ranging from 1 to 50 mg/kg body weight per day or with placebo, for 8 days. On day 6 of treatment the rats were forced to run for 2 h on a level treadmill. Two days after exercise morphological damage in the soleus muscles was quantified using light microscopy and a semi-automatic image analysis system. Creatine kinase (CK) activity was measured before exercise (day 5) and directly after exercise (day 6). The expression of dystrophin in a placebo group and in a group that received 5 mg prednisone/kg body weight per day with and without performing exercise was studied with Western blotting. The effect of prednisone on fibre type distribution was determined with an antibody against fast myosin and the effect of prednisone on the proliferative activity of muscle satellite cells was studied using bromodeoxyuridine (BrdU) immunohistochemistry. Exercise-induced muscle fibre damage varied in a dose-dependent way. In the placebo group the mean (SEM) damaged muscle fibre area was 4% (1%). The groups that received low doses of prednisone, 1 or 2.5 mg/kg per day, showed a similar level of muscle damage. However, with 5 mg prednisone/kg per day the amount of muscle fibre damage [mean (SEM)] was significantly reduced to 1.4% (0.5%) (P ≤ 0.05, Student'st-test). High doses of prednisone had no protective effect. Directly after exercise the CK activity was increased two-fold, except in the group that received 50 mg prednisone/kg body weight per day. No changes in the amount of dystrophin were found after densitometric analysis of the Western blots. Prednisone did not affect the fibre distribution or the labelling index of satellite cells. We conclude that prednisone, given in an appropriate dose, protects muscle fibres against the development of mechanically induced damage, possibly by stabilizing the muscle fibre membranes. This action may explain the beneficial effect of prednisone observed in Duchenne muscular dystrophy patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00869001
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  • 6
    Electronic Resource
    Electronic Resource
    Status of the artificial heart program in Berlin (1985)
    Springer
    World journal of surgery 9 (1985), S. 103-115 
    Details
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le programme d'étude des organes artificiels à Berlin a débuté il y a plus de 20 ans. En ce qui concerne le coeur il s'est attaché à la mise au point d'un coeur artificiel de type électro-pneumatique cependant que la recherche concernait simultanément la mise au point d'un appareil d'assistance cardiaque temporaire et l'étude biologique des matériaux. Les thèmes de ce programme sont les suivants: (a) interactions entre les matériaux naturels et artificiels; (b) développement d'une pompe sanguine et étude de l'usure in vitro; (c) éléments conducteurs et transmission énergétique; (d) mesure des équipements que nécessitent la surveillance et le contrôle automatique du coeur artificiel; (e) études in vivo de la réaction du système circulatoire des organes; (f) entraînement de l'équipe pour l'application clinique du coeur artificiel. Les efforts conjoints des ingénieurs de différentes disciplines et des médecins travaillant ensemble dans le département de chirurgie expérimentale, supportés dans le passé par les partenaires industriels, ont résulté après des études étendues in vitro et in vivo dans l'application clinique d'appareils d'assistance temporaire et dans la réalisation d'un coeur artificiel électro-pneumatique transportable.
    Abstract: Resumen El programa de órganos artificiales se inició en Berlín hace más de 20 años. El mayor énfasis, dentro del programa de asistencia circulatoria y reemplazos mecánicos, ha sido realizado y continúa siéndolo en el desarrollo de un sistema electroneumático de corazón artificial total. Además, se han incluído en el programa de investigación general el desarrollo de un sistema de asistencia temporal junto con estudios en el campo de los biomateriales. Los principales tópicos del programa son: las interacciones entre materiales naturales y artificiales, el desarrollo de bombeo sanguíneo y las pruebas de fatiga in vitro, unidades de propulsión y transmisión energética, equipos de medición necesarios para la vigilancia y control automático del sistema de corazón artificial total, estudios in vivo de la respuesta del sistema circulatorio y de los órganos, el adiestramiento in vivo del personal técnico en cuanto a aptitud y confiabilidad. El esfuerzo coordinado de ingenieras de diferentes disciplinas y de médicos, trabajando continuamente en el departamento de cirugía experimental, apoyado en el pasado por socios industriales, ha resultado, después de extensas investigaciones in vitro e in vivo, en la aplicación clínica de sistemas de asistencia circulatoria temporal y en la realización de un sistema de corazón artificial electro-neumático percutáneo y portátil.
    Notes: Abstract The artificial organs program in Berlin started more than 20 years ago. The main emphasis in the circulatory assist and replacement devices program was and still is on the development of an electro-pneumatic total artificial heart (TAH) system. Additionally, a temporary assist system and investigations in the field of biomaterials are included in the research activities. Topics of the program are: interactions between natural and artificial materials, blood pump development and in vitro fatigue testing, driving units and energy transmission, measurement equipment needed for the surveillance and automatic control of the TAH system, in vivo studies of the response of the circulatory system and the organs, in vivo reliability, and training of the staff for clinical readiness. The joint efforts of engineers of different disciplines and medical doctors, working together in the department of experimental surgery, supported in the past by industrial partners, resulted after extensive in vitro and in vivo investigations in the clinical application of temporary assist devices and the realization of a percutaneous portable, electro-pneumatic total artificial heart system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01656261
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of hypothyroidism on satellite cells and postnatal fiber development in the soleus muscle of rat (1996)
    Springer
    Cell & tissue research 286 (1996), S. 137-144 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Muscle satellite cells ; Hypothyroid ; Proliferation ; Differentiation ; Muscle ; Triiodothyronine ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The effect of hypothyroidism, induced by 4-propyl-2-thiouracil, on muscle satellite cells in vivo and in vitro, and on postnatal muscle fiber development in the soleus muscle of rats during the first 40 days of postnatal life was analyzed. The proliferative activity of satellite cells was determined by means of bromodeoxyuridine incorporation. Creatine kinase activity was used as a marker for differentiation. In vivo, hypothyroidism resulted in smaller fibers in which the amount of sarcoplasm remained in balance with the number of myonuclei. The in vivo labeling data of satellite cells did not indicate a decreased proliferative activity, but the in vitro experiments showed that the hypothyroid rat muscles contained fewer satellite cells that were less active in proliferation and differentiation at the start of culture. Despite this, the bromodeoxyuridine signal increased in time at a similar rate as that in control cultures. From this and because the cells resembled control cells in their response to bFGF, we conclude that hypothyroid satellite cells remain responsive to proliferation stimuli. However, in hypothyroid cultures, the activity of creatine kinase is lower, even at longer culture times. We therefore conclude that hypothyroid status affects muscle precursor cells mainly by depressing their ability to differentiate and fuse with existing myofibers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050682
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  • 8
    Electronic Resource
    Electronic Resource
    Different metabolic adaptation of heart and skeletal muscles to moderate-intensity treadmill training in the rat (1999)
    Springer
    European journal of applied physiology 79 (1999), S. 391-396 
    Details
    ISSN: 1439-6327
    Keywords: Key words Cytoplasmic fatty acid-binding protein ; 3-Hydroxyacyl-coenzyme A dehydrogenase ; Citrate synthase ; 6-Phosphofructokinase ; Endurance training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect was investigated of treadmill training of moderate intensity on the fatty acid-binding protein (FABP) content in relation to parameters of oxidative and glycolytic metabolism. To this end, the cytoplasmic FABP content and the activity of β-hydroxyacyl-coenzyme A dehydrogenase (HAD), citrate synthase (CS), and 6-phosphofructokinase (PFK) were measured in heart, fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles (SOL) of male Wistar rats. To investigate the influence of the amount of training (defined as the product of exercise duration, intensity and frequency), two training groups were created that differed in training frequency (HF, high frequency 5 days · week−1, n=9; LF, low frequency 2 days · week−1, n = 9; the exercise being 20 m · min−1 for 2 h with no gradient, over 6 weeks) and compared with SC, sedentary controls (n = 7). In heart muscle, the cytoplasmic FABP content was 34% higher in HF than in SC but was the same as in LF. The CS and HAD activities were no different in the three groups, suggesting that the capacity to oxidize fatty acids (FA) was not affected by training. The PFK activity was higher (43%) in HF, suggesting a shift towards carbohydrate utilization. The FABP content and HAD activity did not change in SOL and EDL after training whereas the CS activity increased (27%) in SOL and decreased (21%) in EDL in both training groups. In addition, PFK activity in EDL was much higher (113%) in the HF than in SC group. The HF training was associated with a fine-tuning of FA availability and use in heart muscle, and with a more efficient energy production. It is suggested therefore that cytoplasmic FABP could be an early marker of muscle adaptation to training in heart but not in skeletal muscle. The training reinforced the metabolic profile of the skeletal muscles, in particular that of the fast-twitch glycolytic muscle. We concluded that a large amount of training is needed when the effect on both oxidative and glycolytic parameters is to be studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050527
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  • 9
    Electronic Resource
    Electronic Resource
    A comparative study of visual evoked potentials and of retinal nerve fiber layer photography in neuropathies of the optic nerve (1989)
    Springer
    Documenta ophthalmologica 73 (1989), S. 133-138 
    Details
    ISSN: 1573-2622
    Keywords: optic neuropathies ; papillomacular bundle ; retinal nerve fiber layer photography ; visual evoked potentials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The degree of retinal nerve fiber loss within the papillomacular bundle in optic-neuropathies was evaluated from red-free fundus photographs. Visual evoked potentials were obtained from pattern reversal with variable check sizes. A semiquantitative scale was used for the estimation of nerve fiber loss and amplitude reduction of the visual evoked potentials. A significant correlation was found between both. However, a few patients showed rather well-preserved visual evoked potentials with an atrophic nerve fiber layer. Possibly a small number of invisible remaining fibers are able to sustain nearly normal visual evoked potentials. On the other hand, some patients had abnormal visual evoked potentials in the presence of a normal nerve fiber layer. We conclude that evaluation of the nerve fiber layer of the papillomacular bundle without functional testing of the optic nerve is not sufficient to predict degree of foveal integrity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00155031
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  • 10
    Electronic Resource
    Electronic Resource
    A striking correlation between muscle damage after exercise and mitochondrial dysfunction in patients with chronic external ophthalmoplegia (1987)
    Springer
    Journal of inherited metabolic disease 10 (1987), S. 252-255 
    Details
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01811418
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