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External fixation procedures of limb immobilization provide excellent experimental models to study mechanisms involved in muscle disuse atrophy and recovery. Female Wistar rats (7-8 months old) had their right hindlimbs immobilized by an external fixation procedure for 5, 10, 21, and 30 days. Muscle mass of the gastrocnemius and quadriceps muscles was reduced by 41-46% in comparison with contralateral nonimmobilized legs. Acid phosphatase activities were significantly increased after 21 and 30 days of hindlimb immobilization. Histochemical staining for acid phosphatase activities increased in myofibers after the external fixation and also in macrophages in the adjacent extracellular matrix. Matrix metalloproteinase (MMP-2 and MMP-9) activities assessed by gel zymography and also a tissue inhibitor of metalloproteinases (TIMP-1) assessed by Western blot were elevated in the immobilized hindlimb muscles. Our study demonstrated that metalloproteinases are expressed relatively late after limb immobilization and appear to be responsible to a large degree for degradation of the extracellular matrix in experimental disuse atrophy.

Between the ages of 20 and 80 years, humans lose about 20-30% of their skeletal muscle weight. This phenomenon has been termed sarcopenia of old age and is directly involved in the well-being of the aged. With aging, people tend to be less mobile and are frequently bedridden, which exacerbates the muscle weight loss. The molecular mechanisms responsible for the muscle protein breakdown during immobilization in aging have been studied in our laboratory in a model of 24-month-old Wistar rats, immobilized for 4 weeks. Subsequently we investigated the activation of the intracellular and extracellular proteolytic systems in the immobilized muscles. A similar group of young (6-month-old) rats was examined and compared to the older rats. The involvement of NF-kappaB transcription factor in muscle atrophy was assessed in immobilized muscles of young and old animals. There were marked differences in the kinetics and the pattern of NF-kappaB activation in young versus old muscles. It seems that in both young and old animals in the early stages of limb immobilization, an alternative pathway of NF-kappaB activation can be observed. However, in late stages of immobilization, the canonic pathway of NF-kappaB activation (p65/p50 complex with I-kappaB alpha degradation) is predominant. Interestingly, the canonic activation pathway is more prominent in muscles from old animals compared to young ones. The activation of NF-kappaB has been observed also in muscles subjected to acute and intense exercise, implying that inflammatory processes may take place under the conditions of intense exercise. This may cause muscle damage and protein breakdown. Therefore, using NF-kappaB pathway inhibitors may prove beneficial in attenuating NF-kappaB-associated muscle damage in both disuse atrophy and strenuous exercise.

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Background: Serum oxidative stress (OS) level has an important role in the inflammatory process of heart failure. Hypothesis:The study was designed to analyze serum OS levels in chronic heart failure (HF) patients and to examine the relation between OS levels and other clinical and prognostic parameters of HF. Methods: We studied 82 consecutive chronic symptomatic HF patients with systolic LV dysfunction (ejection fraction < 45%). The serum OS level was determined using thermochemiluminescence assay. We compared the serum OS levels with patients' clinical and prognostic parameters. Results: Higher serum OS levels were associated with higher New York Heart Association class (P = .01), worse renal function (serum urea, creatinine, and creatinine clearance) (P<.001) and higher serum levels of hs-C-reactive protein and N-terminal pro brain natriuretic peptide (P = .001, P<.001, respectively). Conclusions: In chronic systolic HF patients, high serum OS levels correlate with advanced disease and known markers of poor prognosis. IntroductionHeart failure (HF) is a major cardiovascular health problem, associated with high mortality and morbidity. Several studies suggested that inflammation has an important role in HF progression. Serum oxidative stress (OS) level is a crucial element of the inflammatory process, owing to the accumulation of reactive oxygen/nitrogen species that might provoke and exacerbate the myocardial damage of the already failing heart. 1 Several medications claim to have at least some beneficial effects through the antioxidant potential. 2 -6 The thermochemiluminescence (TCL) oxidiziability assay (Lumitest Ltd., Haifa, Israel), measures the OS level via photon emission counting from excited carbonyls in biological macromolecules. 7 TCL measurements were previously compared to other well accepted methods, which measure serum oxidative stress level via oxidation of lipids or proteins. 8 As we demonstrated before, TCL measurements were highly correlated with thiobarbituric acid reactive substances-(TBA assay), as well as with protein carbonyl formation (r = 0.99, r = 0.98, P<.01, respectively). 7 In this study, we investigated serum OS levels in chronic HF patients and examined the relation between OS levels and other clinical and laboratory prognostic parameters.