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Biomedical subjects

H J Appell

Publications and source records attributed to H J Appell.

At least 37 records · Page 2Linked to original sources

The possible role of intracellular Ca2+ accumulation for the development of immobilization atrophy.

Little is known about the cellular mechanisms which induce the development of skeletal muscle immobilization atrophy. Initial disturbances in cellular homeostasis seem to occur very early during immobilization. The aim of the study was to investigate whether loss of calcium homeostasis might be of etiological importance for atrophy. Therefore a calcium channel blocker (nifedipine) was administered to mice immobilized for four days, and their soleus muscle was investigated comparatively to immobilized animals without nifedipine. The immobilized muscles showed an atrophy of about 15% which was not the case in nifedipine-treated immobilized muscles. Ultrastructural alterations (lysosomes, mitochondrial damage) were found predominantly in the immobilized muscles, but rarely with nifedipine. It was concluded that nifedipine protected the muscle fibers probably against calcium overload, thereby avoiding an autophagic response and an impairment of mitochondrial respiratory function.

Animals↗

Endothelium-derived oxidative stress may contribute to exercise-induced muscle damage.

In exercise-induced muscle damage, oxidative stress derived from the liberation of reactive oxygen species (ROS) is assumed to be of etiological importance. Xanthine oxidase (XO) located in capillary endothelium is one of the possible sources for ROS, mainly investigated so far under conditions of ischemia/reperfusion. XO can be inhibited by allopurinol. To investigate the contribution of XO for the oxidative stress-induced development of muscle damage, mice were subjected to a single bout of exhaustive running exercise. Another exercised group received allopurinol. The reduced form of glutathione (GSH) was measured to estimate the amount of oxidative stress in soleus muscle, and the same muscle was examined in the light and electron microscope at different periods of time (0, 48, 96 h) after exercise. While exercise alone resulted in a marked reduction of GSH indicative for oxidative stress, which only recovered at 96 h, the administration of allopurinal to exercised animals induced a complete recovery already at 48 h after exercise. Muscle damage was more pronounced in the exercised animals which had not been treated with allopurinol. It is concluded that endothelium-derived ROS contribute reasonably to oxidative stress to exercised muscle and to fiber and capillary damage.

Allopurinol↗

Nifedipine diminishes exercise-induced muscle damage in mouse.

The purpose of this study was to evaluate the effects of a calcium channel blocker (nifedipine) on the severity of muscle damage induced by intensive exercise. Male Charles River mice were assigned to four groups (8 mice/group): normal control (C), nifedipine (N), nifedipine and exercise (N + E) and exercise (E). The animals of the C group were not submitted to any exercise nor to drug administration. The animals of the N group received 1 mg.kg-1 per day of nifedipine (Adalat 10 mg, Bayer AG), per os, during 3 days. The mice of the N + E group were submitted to a treadmill run (0 degree slope) at 1000 m.h-1 (80% of their maximal speed) for 1 hour. In this group, the administration of the drug was under the same conditions as for the N group. The administration started 24 h before the run. The E group was submitted to the same exercise protocol as the animals of N + E group. The soleus muscle was excised for light and electron microscopic evaluation using routine histological techniques. In the C and N groups no morphological alterations were detected. In the E group the number of alterations of striated pattern was twice that in the N + E group. The number of fibres with central nuclei was 35% in the E group but only 8% in the N + E group. The total number of damaged fibres was significantly higher in the E group. The results suggest that nifedipine may give protection to exercise-induced skeletal muscle damage in mouse, probably because the blocking of channels impaired Ca2+ influx; and the results of this study therefore confirm earlier contentions about the possible role of calcium ions in producing muscle damage after work.

Animals↗

Exercise, muscle damage and fatigue.

Fatigue as a functional sign and muscle damage as a structural sign can be observed after prolonged exercise like marathon running or after strenuous exercise, especially with the involvement of eccentric contractions. For fatigue due to prolonged exercise, hypoxic conditions and the formation of free oxygen radicals seem to be of aetiological importance, resulting in an elevated lysosomal activity. Eccentric exercise of high intensity rather results in a mechanical stress to the fibres. Although these different mechanisms can be discerned experimentally, both result in similar impairments of muscle function. A good training status may attenuate the clinical signs of fatigue and muscle damage. The symptoms and events occurring during delayed onset of muscle soreness (DOMS) can be explained by a cascade of events following structural damage to muscle proteins.

Animals↗

[Lack of fatigue of the musculature in patients after immobilization--a paradox?].

The isometric strength of knee extensors was measured in patients six weeks after cruciate ligament surgery over a contraction period of 30 sec. The characteristics of the graph obtained form the measurement system were compared to the graphs of uninjured knee extensor muscles. Apart from strength reductions, as expected for atrophic muscle, the pattern of the strength graph led to the impression that these muscles did not fatigue during prolonged contraction. This paradoxical phenomenon can be explained by the existence of central inhibitory mechanisms.

Anterior Cruciate Ligament↗

Potentiation of cytostatic but not cytolytic activity of murine macrophages after running stress.

The influence of physical exercise on the tumortoxicity of peritoneal murine macrophages (PMM) was investigated. The tumortoxic activity was discriminated into cytostatic and cytolytic effects. Cytostatic activity of PMM on tumor cells in vitro was studied using the proliferation assay of S-180 sarcoma cells. Cytolytic activity was monitored using the method of the slow form of antibody-dependent cellular cytotoxicity (ADCC) on SW 707 tumor cells. After a single exhaustive running session an increased cytostatic activity of PMM was observed as compared to PMM of sedentary animals. In PMM mediated ADCC no difference was detected between trained and untrained animals. It is concluded that physical exercise is a complex stimulus for macrophages that, at least in parts, triggers their cytotoxic activity against tumor cells.

Animals↗

Muscular atrophy following immobilisation. A review.

Muscular atrophy regularly occurs as a consequence of immobilisation or disuse after sports injuries. Several experimental models deal with muscle atrophy and are suitable for investigations of the underlying mechanisms of muscle atrophy. Strength loss is the most evident response to atrophy. Muscle strength decreases most dramatically during the first week of immobilisation; little further weakening occurs later on. This is reflected in changes in the EMG of disused muscles and can also be observed in muscle weight and size of muscle fibres. Slow muscles with predominantly oxidative metabolism are most susceptible to atrophy as indicated by various findings: slow muscle fibers show greater atrophy than fast fibres; their relative and probably absolute number is decreased in atrophic muscles; in addition, the oxidative enzyme content is most severely affected by disuse. Atrophic muscle is characterised by a catabolic metabolism. The rate of protein synthesis is reduced and that of protein breakdown increased. Autophagic activities probably play an important role in early stages of muscular atrophy. The oxygen supply to disused muscle may be impaired, although myoglobin content is increased in atrophic muscle. The complete loss of mitochondrial function during the first days of disuse may be of aetiological importance. The amount of connective tissue is increased in atrophic muscle and surrounding periarticular tissue which may lead into a vicious circle of musculoskeletal degeneration. An almost complete recovery from atrophy is possible, yet often the recovery phase is much longer than the total immobilisation period.

Animals↗

Fine structural changes in electrostimulated human skeletal muscle. Evidence for predominant effects on fast muscle fibres.

Physical education students were subjected to electrical stimulation of relatively high frequency and current amplitude for 19 days. A quantitative study of several morphological parameters was performed on biopsy samples from gastrocnemius, using stereological methods at both light and electron microscopic levels. The main results were: muscle fibre size was increased; nuclear volume was also increased, suggesting that a proliferation of nuclei had occurred; this was paralleled by an increased content of nuclear DNA. The size of single myonuclei was increased, and their heterochromatin fraction was decreased, these changes being most pronounced in type II fibres. The increase in the mitochondrial fraction was also greatest in type II fibres. It is concluded that this type of electrical stimulation has predominant effects on type II fibres.

Cell Nucleus↗

Satellite cell activation in human skeletal muscle after training: evidence for muscle fiber neoformation.

In subjects who had undergone monopedal bicycle ergometer work for 30 min 4 days a week for 6 weeks under aerobic conditions, biopsies from the M. vastus lateralis were studied in the light and electron microscope. In some cases very small myofibers with central nuclei were found. At the ultrastructural level, these fibers turned out to be myotubes. The satellite cells occasionally appeared to be activated and to fuse with muscle fibers. It was concluded that these observations represented evidence for the development of new muscle fibers.

Adaptation, Physiological↗

[Possibility of the transformation of muscle fibers by training and the significance of muscle biopsies for recognizing talent in sports].

Different methods for skeletal muscle fibre typing are reported. The demonstration of the ATPase, which is mostly used in the recent past, allows for the differentiation of four types, called I, IIC, IIA, and IIB. Using biochemical methods, a further division based on different myosin types is possible. The transformation of distinct fibre types by means of special training programmes may have been overestimated in the past and is assumed to be of minor importance in sports. Taking muscle biopsies for search of talents in sports does not seem to be meaningful and is unethical.

Aptitude↗

[Rhabdomyolysis in a bodybuilder using anabolic steroids].

The clinical course and the laboratory findings of a massive rhabdomyolysis in a male bodybuilder is presented. Particularly spectacular are the light- and electron-microscopical pictures of the histological findings. The acute renal failure as the most important and major life-threatening complication of the rhabdomyolysis is considered and the successful therapeutic procedure is described. The probability of a causal relation between anabolic steroids and rhabdomyolysis is discussed as well as the resulting consequences for the care of athletes in sports medicine.

Adult↗

Muscle biopsy--still a matter of methodological considerations.

A method of open muscle biopsy is described which is not so invasive for the patient and not traumatic for the muscle tissue. The biopsy is performed with the patient under local cutaneous anesthesia. The sample can be obtained from a defined part of the muscle. It allows morphological-quantitative evaluation of a sufficient amount of fibers to arrive at reliable results. The advantages of the described method compared with other open and needle biopsy procedures, especially with regard to the method of anesthesia, are discussed.

Anesthesia, Local↗

Effect of electrical stimulation of high and low frequency on maximum isometric force and some morphological characteristics in men.

The effects of two methods of electrical stimulation on maximum isometric force, calf girth, and skinfold thickness of stimulated and nonstimulated (contralateral) legs were studied. Thirty-six male volunteers, divided into three groups, participated in the experiment. Groups I and II were subjected to the procedure of electrical stimulation of m. triceps surae daily for a period of 21 days. Group I was stimulated by an alternating current of low frequency (50 Hz); group II was also stimulated by an alternating current but of higher frequency (2000 Hz). Group III served as control group. In groups I and II significant increases of the maximum isometric force (as measured on an electronic dynamometer) of the stimulated (50.3% and 58.8%) and also of the nonstimulated (contralateral) muscles (39.7% and 32.2%) were found. In group III no significant increase of the maximum isometric force was registered. After the period of stimulation, the skinfold thickness was notably reduced by 21.6% in group II, and calf girth was enlarged in both experimental groups. Relatively large changes were realized in the calf girth and the skin-fold thickness of the nonstimulated legs. The changes in group III were insignificant. It is concluded that electrical stimulation with low as well as high frequencies exerts great effects on muscle force.

Adult↗

Effects of electrical stimulation of different frequencies on the myonuclei and fiber size in human muscle.

Male physical education students were subjected to electrical stimulation for a period of 21 days. The stimulation was performed with alternating currents of rectangular wave form. Group I was stimulated with a frequency of 50 Hz, group II with a frequency of 2000 Hz. Before and after the experimental period, biopsies were taken from the m. gastrocnemius. The muscle fiber size and the number and size of nuclei was estimated at the light microscopic level using stereological methods. The fiber size was significantly increased only in group I. The nuclear number and the nuclear size increased significantly in both groups leading to a higher nuclear volume per unit tissue volume. It was assumed that the proliferation of nuclei is correlated to satellite cell proliferation resulting probably in hypertrophy or hyperplasia of electrostimulated skeletal muscle.

Adult↗

Stereological analysis of capillaries in electrostimulated human muscles.

The effects of two methods of electrical stimulation on the capillary density in skeletal muscle was studied. Twenty-two male physical education students randomly divided into two groups participated in the experiment. Groups I and II were subjected to the procedure of electrical stimulation of m. triceps surae daily for a period of 21 days. Group I was stimulated by an alternating current of relatively low frequency (50 Hz), and group II was stimulated by an alternating current of relatively high frequency (2000 Hz). Biopsy specimens were obtained from the lateral portion of m. gastrocnemius 1 week before the stimulation and 1 day after the completion of the stimulation period. The capillary network was analyzed using morphometric and stereological techniques. Significant changes were found for capillary number in cross section, capillary density, intercapillary distance, tissue cylinder corresponding to one capillary (Krogh's cylinder) in both groups, and for capillary number-to-fiber area ratio in group I. Differences between the results of groups I and II were not significant in any cases. The changes observed speak in favor of an improved capillary supply to skeletal muscle after electrical stimulation.

Adult↗

Morphology of immobilized skeletal muscle and the effects of a pre- and postimmobilization training program.

The hind limbs of mice were immobilized with plaster cast for different periods of time, and the atrophy of the anterior tibial muscle was examined by measuring fiber cross sections. In a second series of experiments, mice were trained on a treadmill before and after immobilization. The most pronounced decrease in fiber diameters was observed during the 1st week; during prolonged immobilization, only a moderate atrophy occurred. Red fibers were found to be more susceptible to immobilization atrophy than white fibers. The ultrastructural observations extended to loss and fragmentation of myofibrils, mitochondria, and the sarcotubular system. Some fibers split and appeared to undergo segmental necrosis, which was followed by invasion of leucocytes into the muscle. Still while immobilized, the muscles exhibited a regenerative capacity; satellite cells differentiated to myoblasts, which fused to myotubes, being the precursors of new muscle fibers. This was already observed during the 1st week of immobilization. The effect of training after immobilization was documented by an increase of fiber diameters. The ultrastructural alterations, however, in these muscles were severe; it was concluded that a postimmobilization training has to be undertaken very carefully. When the muscles were trained before immobilization, the atrophy was almost negligible. A preimmobilization training can probably prevent the muscle from developing severe atrophy.

Animals↗

Proliferation of motor end-plates induced by increased muscular activity.

The effects of muscular activity on the motor end-plates were studied. To simulate an overload training on the diaphragm, Japanese waltzer mice were subjected to hypobaric hypoxia (simulated altitude of 3000 m) for 7 and 14 days. After demonstration of the end-plates by AChE-staining, their size and total number in the sternal part of the diaphragm were measured at the light microscopic level. The end-plate regions were enlarged after 7 days and were increased in number after 14 days. These changes can probably be explained by the mechanisms of terminal and collateral sprouting. The electron-microscopic examination showed no ultrastructural peculiarities in either of the experimental groups. The muscle fibers of the trained animals showed a strong reaction of AChE; thus, it was suggested that end-plate proliferation was myogenically induced.

Animals↗