It is known that non-cachectic patients with chronic obstructive pulmonary disease (COPD) respond well to pulmonary rehabilitation, but whether cachectic COPD patients are capable of adaptive responses is both important and unknown.10 cachectic and 19 non-cachectic COPD patients undertook high-intensity cycling training, at the same relative intensity, for 45 min?day -1 , 3 days?week -1 for 10 weeks. Before and after rehabilitation vastus lateralis muscle biopsies were analysed morphologically and for the expression of muscle remodelling factors (insulin-like growth factor (IGF)-I, myogenic differentiation factor D (MyoD), tumour necrosis factor (TNF)-a, nuclear factor (NF)-kB and myostatin) and key components of ubiquitin-mediated proteolytic systems (muscle ring finger protein (MURF)-1 and Atrogin-1).Rehabilitation improved peak work-rate and the 6-min walk distance similarly in non-cachectic (18¡3% and 42¡13 m, respectively) and cachectic (16¡2% and 53¡16 m, respectively) patients, but quality of life only improved in non-cachectic COPD. Mean muscle fibre cross-sectional area increased in both groups, but significantly less in cachectic (7¡2%) than in non-cachectic (11¡2%) patients. Both groups equally decreased the proportion of type IIb fibres and increased muscle capillary/fibre ratio. IGF-I mRNA expression increased in both groups, but IGF-I protein levels increased more in non-cachectic COPD. MyoD was upregulated, whereas myostatin was downregulated at the mRNA and protein level only in non-cachectic patients. Whilst rehabilitation had no effect on TNF-a expression, it decreased the activation of the transcription factor NF-kB in both groups by the same amount. Atrogin-1 and MURF-1 expression were increased in cachectic COPD, but it was decreased in non-cachectic patients.Cachectic COPD patients partially retain the capacity for peripheral muscle remodelling in response to rehabilitation and are able to increase exercise capacity as much as those without cachexia, even if they exhibit both quantitative and qualitative differences in the type of muscle fibre remodelling in response to exercise training.

The purpose of the present study was to investigate the possible relationship between a change in Thr(389) phosphorylation of p70S6 kinase (p70(S6k)) after a single resistance training session and an increase in skeletal muscle mass following short-term resistance training. Eight male subjects performed an initial resistance training session in leg press, six sets of 6RM with 2 min between sets. Muscle biopsies were obtained from the vastus lateralis before (T1) and 30 min after the initial training session (T2). Six of these subjects completed a 14-week resistance-training programme, three times per week (nine exercises, six sets, 6RM). A third muscle biopsy was obtained at the end of the 14-week training period (T3). One repetition maximum (1RM) squat, bench press and leg press strength as well as fat-free mass (FFM, with dual energy X-ray absorptiometry) were determined at T1 and T3. The results show that the increase in Thr(389) phosphorylation of p70(S6k) after the initial training session was closely correlated with the percentage increase in whole body FFM (r = 0.89, P < 0.01), FFM(leg) (r = 0.81, P < 0.05), 1RM squat (r = 0.84, P < 0.05), and type IIA muscle fibre cross sectional area (r = 0.82, P < 0.05) after 14 weeks of resistance training. These results may suggest that p70(S6k) phosphorylation is involved in the signalling events leading to an increase in protein accretion in human skeletal muscle following resistance training, at least during the initial training period.

Alpha-dystroglycanopathies such as Walker Warburg syndrome represent an important subgroup of the muscular dystrophies that have been related to defective O-mannosylation of alpha-dystroglycan. In many patients, the underlying genetic etiology remains unsolved. Isolated muscular dystrophy has not been described in the congenital disorders of glycosylation (CDG) caused by N-linked protein glycosylation defects. Here, we present a genetic N-glycosylation disorder with muscular dystrophy in the group of CDG type I. Extensive biochemical investigations revealed a strongly reduced dolichol-phosphate-mannose (Dol-P-Man) synthase activity. Sequencing of the three DPM subunits and complementation of DPM3-deficient CHO2.38 cells showed a pathogenic p.L85S missense mutation in the strongly conserved coiled-coil domain of DPM3 that tethers catalytic DPM1 to the ER membrane. Cotransfection experiments in CHO cells showed a reduced binding capacity of DPM3(L85S) for DPM1. Investigation of the four Dol-P-Man-dependent glycosylation pathways in the ER revealed strongly reduced O-mannosylation of alpha-dystroglycan in a muscle biopsy, thereby explaining the clinical phenotype of muscular dystrophy. This mild Dol-P-Man biosynthesis defect due to DPM3 mutations is a cause for alpha-dystroglycanopathy, thereby bridging the congenital disorders of glycosylation with the dystroglycanopathies.

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