Diagnostische Bedeutung von Muskelbiopsien bei metabolischen Myopathien

Summary In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.

Mit Unterstützung durch die DFG und die Friedrich Baur Stiftung, München     

Comparison of glutamate metabolism in low K (LK), high K and high glutathione (HK/HG) and high K and low glutathione (HK/LG) dog red blood cells

The reasons for the high accumulation of glutamate (Glu), aspartate (Asp) and glutamine (Gin) in high K and high glutathione (HK/HG) dog red blood cells (DRBCs) have been explained as due to enhanced Glu/Asp influxes. However, in our study, Glu/Asp influxes in high K and low glutathione (HK/LG) DRBCs were low, whereas their cellular Asp and Gin contents were high. In low K (LK) DRBCs, there were also other variant cells with high Asp accumulation, but extremely low Glu/Asp influxes. So, the high amino acid accumulation in DRBCs of these new variants might not be due to Glu/Asp influxes. To examine the high accumulation of these amino acids in these variant DRBCs, first, LK and HK/LG DRBCs were classified into two subgroups with their Na-dependent Glu/Asp influxes; one had clear Na-dependent Glu/Asp transport (GAT⁺), and the other failed to have any transport (GAT⁻). The influxes of both Glu and Asp in HK/HG DRBCs were the highest, and the order was HK/HG>LK/GAT⁺>HK/LG/GAT⁺>>LK/GAT⁻=HK/LG/GAT⁻. LK/GAT⁺ cells represented normal DRBCs. Glu/Asp influxes were only trace in both LK/GAT⁻ and HK/LG/GAT⁻ cells, but Glu and Asp concentration was high in HK/LG/GAT⁻ cells whereas Asp concentration was high in LK/GAT⁻ cells. In HK/HG cells, the conversion of Glu into Gin in whole cells was several fold higher than in the other cell groups due to the differing amount of the substrate of glutamine synthetase, Glu, but glutamine synthetase activity itself was not different among these cell groups. Furthermore, glutamine synthetase and glutaminase activities were not different among the cell groups. Therefore, these enzymes were not involved in the high amino acid accumulation.     

Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation

Seven male subjects performed repeated bouts of high-intensity exercise, on a cycle ergometer, before and after 6 d of creatine supplementation (20 g Cr H₂O day^-1). The exercise protocol consisted of five 6-s exercise periods performed at a fixed exercise intensity, interspersed with 30-s recovery periods (Part I), followed (40 s later) by one 10 s exercise period (Part II) where the ability to maintain power output was evaluated. Muscle biopsies were taken from m. vastus lateralis at rest, and immediately after (i) the fifth 6 s exercise period in Part I and (ii) the 10 s exercise period in Part II. In addition, a series of counter movement (CMJ) and squat (SJ) jumps were performed before and after the administration period. As a result of the creatine supplementation, total muscle creatine [creatine (Cr) + phosphocreatine (PCr)] concentration at rest increased from (mean + SEM) 128.7 (4.3) to 151.5 (5.5)mmolkg^_1 dry wt (P < 0.05). This was accompanied by a 1.1 (0.5) kg increase in body mass (P < 0.05). After the fifth exercise bout in Part I of the exercise protocol, PCr concentration was higher [69.7 (2.3) vs. 45.6 (7.5) mmol kg“‘ dry wt, P < 0.05], and muscle lactate was lower [26.2 (5.5) vs. 44.3 (9.9) mmol kg”¹ dry wt, P < 0.05] after vs. before supplementation. In Part II, after creatine supplementation, subjects were better able to maintain power output during the 10-s exercise period (P < 0.05). There was no change in jump performance as a result of the creatine supplementation (P > 0.05). These findings show that enhanced fatigue resistance during short duration high-intensity exercise following creatine supplementation is associated with a greater availability of PCr and a lower accumulation of lactate in the muscle. The finding that jump performance was not enhanced suggests that short-term creatine feeding does not influence peak power output.     

Increase of food intake induced by glucagon in the rat

The effect of intraperitoneal administration of saline, glucose (25 mg/100 g b.w.), insulin (0.025 U/100 g b.w.) and glucagon (50 micrograms/kg b.w.) on glycemia, liver glycogen concentration and food intake was studied on 104 male adult Wistar rats. When saline was injected the amount of food ingested was similar to that expected at the metabolic moment selected for the tests. Glucose administration did not reduce food intake but both insulin and glucagon provoked a threefold increase during the 60 minutes ensuing the injection. The overall ingestion of food during the 24 hours after the injection of the hormones was significantly higher (about 10%) than the control values during the preceding or the succeeding 24 hours. A hyperphagic, rather than a hypophagic effect of glucagon administration is possibly related to the small dose used in the experiments. The mechanisms involved in the increase of food intake due to glucagon are discussed in terms of acceleration of the metabolic reactions that normally prevent large drops of glycemia as glucose utilization proceeds during the inter-meal periods and that in physiological conditions build up until the need for food arises.     

Impaired Leydig Cell Function In Vitro in Testicular Tissue from Human Males with "Sertoli Cell Only" Syndrome

Testicular histopathology in patients with "Sertoli Cell Only" Syndrome is characterized by absence of germinal cells. Some of these patients have high levels of LH in their peripheral blood as well as subnormal serum testosterone levels. This indicates a possible correlation between the lack of germinal cells and an impairment of Leydig cell steroidogenic activity. It has previously been shown that in vitro conversion of tritiated steroid precursors within testicular tissue indicates the Leydig cell steroidogenic activity. In this study we have investigated whether or not testicular tubular cell disorder with lack of germinal cells is related to impairment of the intratesticular steroid metabolism in vitro. Ten patients with testicular histopathology characteristic of "Sertoli cell only" syndrome were investigated and their steroid metabolism patterns were compared with those of 22 control patients. Leydig cell dysfunction was found in the group of patients with SOS; 17 alpha-hydroxylation was significantly lower and the production of 20 alpha-dihydroprogesterone was significantly higher, as compared to the control patients. The Leydig cell impairment may be due to a disturbed influence from the damaged tubules.     

Surgical remodeling of the silhouette by aspiration lipolysis or selective lipectomy

The author, a pioneer in originating the technique of suction lipectomy, discusses in detail the pathophysiology of the fat cell and fat metabolism. In addition, he describes the surgical means by which, since 1977, he has popularized this innovative new approach to the treatment of unsightly fat deposits in many sites in the body, including the thighs, buttocks, abdomen, hips, arms, ankles, breasts, and submental regions.     

Effects of sensory deafferentation on glucose metabolism of muscles during locomotion

We measured the uptake of a radiolabeled analogue of glucose ([3H]FDG) into muscles during treadmill walking so as to determine whether sensory deafferentation of a limb affects the muscles' metabolic response to the exercise. The muscles on the deafferented side took up less tracer than those in the intact side with exercise, but not at rest. Extensor muscles were more affected than flexors by deafferentation. This agrees with the proposal that "reflex" inputs adjust the level of recruitment of motor units by central pattern generators.     

Alterations in alanine metabolism in diabetic dogs during short-term treatment with an artificial B cell

Summary The flux rates of plasma glucose and alanine were studied isotopically (6-³H-glucose and U-¹⁴C-alanine simultaneously) in resting chronically diabetic dogs during short-term treatment with an artificial B cell where the insulin was infused into a peripheral vein. Despite perfect blood glucose control and normal glucose flux rates, the concentration and rates of appearance and disappearance of alanine were significantly elevated in the diabetic animals before, during and after an exogenous glucose load. The incorporation of the carbon moiety of alanine into circulating glucose was also increased, but diminished to a near-normal extent when exogenous glucose was given. The plasma clearance rates for alanine in the diabetic dogs were normal throughout the study. It is concluded that normal blood glucose control in diabetes does not necessarily mean normalization of the entire metabolic network. On the basis of peripheral hyperinsulinaemia alanine formation from glucose and branched chain amino acids is elevated in muscle. This may explain increased flux of alanine despite normal blood glucose control.     

Are the metabolic characteristics of congenital intraspinal lipoma cells identical to,or different from normal adipocytes?

Congenital intraspinal lipomas are frequently responsible for progressive neurological deficits caused by distortion or compression of the nervous system. Since fat metabolism in these lesions has not been previously studied, the aim of this study was to determine whether intraspinal lipoma cells behave like lipomas or like normal adipocytes. In 11 patients, intraspinal lipoma cells were compared with normal adipocytes isolated from adjacent subcutaneous adipose tissue for the following parameters: lipoprotein lipase (LPL), lipogenesis from U¹⁴C glucose, ß-receptor number, adenylate cyclase activity, cyclic AMP production, and lipolysis in response to ß- and ₂-adrenergic agonists. No significant difference between these two cell populations was found, suggesting that intraspinal lipomas are not lipomatous tumors, but hamartomatous lesions capable of growth and regression along with the changes in the rest of the fatty pool. This emphasizes the danger of an abnormal weight gain, as well as the possible usefulness of an hypocaloric diet in patients who worsen in spite of previous surgery.Research supported by INSERM (CRL 824005 and CRE 854010) and the D.G.R.