Recently CFS has been included in

Recently, CFS has been included in the group “low cystine and glutamine syndromes,” which are characterized by a combination of abnormally low plasma levels of these two aminoacids, as well as reduced natural killer cell activity, and increased rates of urea production [13]. Some studies indicated that there wasn’t a consistent correlation between CFS symptoms and changes in muscle morphology (fiber-type prevalence, fiber size, degenerative features, or mitochondrial abnormalities) and physiological contractile properties [14]. Recent studies contradict this statement [12]. Oxidative c-di-AMP sale related to mitochondrial activity can cause increased production of reactive oxygen species (ROS), leading to oxidative damage that can be correlated with an increase in muscle fatigability during normal aging [15]. Both these latter conditions are also seen in the muscle specimens derived from CFS patients [16]. We therefore examined whether (i) skeletal muscle is a site of damage, which induces reductions of functional activity; and whether (ii) muscle damage is a consequence of impairment of the oxidant/antioxidant system.
Methods The study population consisted of six patients with CFS (four males and two females; mean age 35.7 ± 1.6 years) and three patients (one male and two females; mean age 48.2 ± 1.7 years) suffering from fibromyalgia (FS), used only as a positive control for lipid analysis. All patients were selected at the Center for the Study of CFS of the University of Chieti on the basis of the CDC criteria [17]. Six healthy subjects who underwent orthopedic surgery and who were sex- and age-matched were used as controls. Biopsy specimens (0.01–0.5 g) were obtained from the vastus lateralis on the basis of the principles indicated by A. G. Engel and C. Franzini-Armstrong [18] and the samples were immediately frozen in liquid nitrogen for the following determinations.
Discussion The International CFS study group noted that CFS accounts for only a small percentage of patients affected by fatigue. Other classified subgroups are prolonged fatigue (when it persists for at least one month and in most cases is transitory) and chronic idiopathic fatigue (when fatigue is reported for a period longer than six months but does not meet the Centers for Disease Control (CDC) diagnostic criteria for CFS). Muscle weakness and pain are the primary symptoms in CFS, suggesting that muscle is the major target of the pathology. A previous study showed that low acylcarnitine content in the serum of CFS patients is related to reduced energy production by muscle mitochondria [8]. Furthermore, phosphorus magnetic resonance spectroscopy in CFS patients demonstrated reduced oxidative metabolism in muscle as compared with sedentary controls [9]. A consequence of mitochondrial dysfunction is increased production of free radicals. The results obtained in the present study show that oxidative damage may contribute to the pathogenesis of CFS. We previously found age-dependent increases in oxidative damage to both lipids and DNA in healthy control subjects [15], which may reflect either increased production of free radicals or insufficient free radical scavenging or repair systems. The present results indicate that the activity of antioxidant enzyme systems is significantly increased in CFS, which may be compensatory for oxidative stress. The level of glutathione was also significantly increased, which may explain a decrease in the functional capacity of the muscles [32]. Similarly glutathione is increased in muscle samples from healthy subjects after a bout of high intensity exercise [33], which may induce oxidative stress. However, despite the similarities, there are differences in the state of antioxidant enzyme and/or oxidative damage repair systems between CFS patients and healthy subjects. Information about age-associated changes in the efficiency of repair processes to remove oxidatively damaged molecules is quite fragmentary, and a consistent pattern of age-associated changes in the activities of individual antioxidative enzymes has not been detected [34].