Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.

CONTEXT: Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass. OBJECTIVE: To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients. METHODS: Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or resistance exercise training (n = 10). Type I and II muscle fiber distribution, fiber size, and myonuclear and capillary contents were determined by immunohistochemistry. RESULTS: Significant decreases in type I (from 7401 ± 1183 to 6489 ± 1293 µm2, P < .05) and type II (from 6225 ± 1503 to 5014 ± 714 µm2, P < .05) muscle fiber size were observed in the usual care group. In addition, type I and type II individual capillary-to-fiber ratio (C/Fi) declined (-12% ± 12% and -20% ± 21%, respectively, P < .05). In contrast, significant increases in type I (from 6700 ± 1464 to 7772 ± 1319 µm2, P < .05) and type II (from 5248 ± 892 to 6302 ± 1385 µm2, P < .05) muscle fiber size were observed in the training group, accompanied by an increase in type I and type II muscle fiber myonuclear contents (+24% ± 33% and +21% ± 23%, respectively, P < .05) and type I C/Fi (+18% ± 14%, P < .05). CONCLUSION: The onset of ADT is followed by a decline in both type I and type II muscle fiber size and capillarization in PCa patients. Resistance exercise training offsets the negative impact of ADT and increases type I and II muscle fiber size and type I muscle fiber capillarization in these patients.

Intradialytic Protein Ingestion and Exercise do Not Compromise Uremic Toxin Removal Throughout Hemodialysis.

OBJECTIVE: Dietary protein and physical activity interventions are increasingly implemented during hemodialysis to support muscle maintenance in patients with end-stage renal disease (ESRD). Although muscle maintenance is important, adequate removal of uremic toxins throughout hemodialysis is the primary concern for patients. It remains to be established whether intradialytic protein ingestion and/or exercise modulate uremic toxin removal during hemodialysis. METHODS: We recruited 10 patients with ESRD (age: 65 ± 16 y, BMI: 24.2 ± 4.8 kg/m2) on chronic hemodialysis treatment to participate in this randomized cross-over trial. During hemodialysis, patients were assigned to ingest 40 g protein or a nonprotein placebo both at rest (protein [PRO] and placebo [PLA], respectively) and following 30 min of exercise (PRO + exercise [EX] and PLA + EX, respectively). Blood and spent dialysate samples were collected throughout hemodialysis to assess reduction ratios and removal of urea, creatinine, phosphate, cystatin C, and indoxyl sulfate. RESULTS: The reduction ratios of urea and indoxyl sulfate were higher during PLA (76 ± 6% and 46 ± 9%, respectively) and PLA + EX interventions (77 ± 5% and 45 ± 10%, respectively) when compared to PRO (72 ± 4% and 40 ± 8%, respectively) and PRO + EX interventions (73 ± 4% and 43 ± 7%, respectively; protein effect: P = .001 and P = .023, respectively; exercise effect: P = .25 and P = .52, respectively). Nonetheless, protein ingestion resulted in greater urea removal (P = .046) during hemodialysis. Reduction ratios and removal of creatinine, phosphate, and cystatin C during hemodialysis did not differ following intradialytic protein ingestion or exercise (protein effect: P > .05; exercise effect: P>.05). Urea, creatinine, and phosphate removal were greater throughout the period with intradialytic exercise during PLA + EX and PRO + EX interventions when compared to the same period during PLA and PRO interventions (exercise effect: P = .034, P = .039, and P = .022, respectively). CONCLUSION: The removal of uremic toxins is not compromised by protein feeding and/or exercise implementation during hemodialysis in patients with ESRD.

Protein synthesis rates of muscle, tendon, ligament, cartilage, and bone tissue in vivo in humans.

Skeletal muscle plasticity is reflected by a dynamic balance between protein synthesis and breakdown, with basal muscle tissue protein synthesis rates ranging between 0.02 and 0.09%/h. Though it is evident that other musculoskeletal tissues should also express some level of plasticity, data on protein synthesis rates of most of these tissues in vivo in humans is limited. Six otherwise healthy patients (62±3 y), scheduled to undergo unilateral total knee arthroplasty, were subjected to primed continuous intravenous infusions with L-[ring-13C6]-Phenylalanine throughout the surgical procedure. Tissue samples obtained during surgery included muscle, tendon, cruciate ligaments, cartilage, bone, menisci, fat, and synovium. Tissue-specific fractional protein synthesis rates (%/h) were assessed by measuring the incorporation of L-[ring-13C6]-Phenylalanine in tissue protein and were compared with muscle tissue protein synthesis rates using a paired t test. Tendon, bone, cartilage, Hoffa's fat pad, anterior and posterior cruciate ligament, and menisci tissue protein synthesis rates averaged 0.06±0.01, 0.03±0.01, 0.04±0.01, 0.11±0.03, 0.07±0.02, 0.04±0.01, and 0.04±0.01%/h, respectively, and did not significantly differ from skeletal muscle protein synthesis rates (0.04±0.01%/h; P>0.05). Synovium derived protein (0.13±0.03%/h) and intercondylar notch bone tissue protein synthesis rates (0.03±0.01%/h) were respectively higher and lower compared to skeletal muscle protein synthesis rates (P<0.05 and P<0.01, respectively). Basal protein synthesis rates in various musculoskeletal tissues are within the same range of skeletal muscle protein synthesis rates, with fractional muscle, tendon, bone, cartilage, ligament, menisci, fat, and synovium protein synthesis rates ranging between 0.02 and 0.13% per hour in vivo in humans. Clinical trial registration: NTR5147.

One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients.

OBJECTIVES: Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women. DESIGN AND PARTICIPANTS: Twenty-six older patients (75 ± 1 years) undergoing elective total hip arthroplasty participated in this observational study. MEASUREMENTS: On hospital admission and on the day of discharge, computed tomographic (CT) scans were performed to assess muscle cross-sectional area (CSA) of both legs. During surgery and on the day of hospital discharge, a skeletal muscle biopsy was taken from the m. vastus lateralis of the operated leg to assess muscle fiber type-specific CSA. RESULTS: An average of 5.6 ± 0.3 days of hospitalization resulted in a significant decline in quadriceps (-3.4% ± 1.0%) and thigh muscle CSA (-4.2% ± 1.1%) in the nonoperated leg (P < .05). Edema resulted in a 10.3% ± 1.7% increase in leg CSA in the operated leg (P < .05). At hospital admission, muscle fiber CSA was smaller in the type II vs type I fibers (3326 ± 253 µm2 vs 4075 ± 279 µm2, respectively; P < .05). During hospitalization, type I and II muscle fiber CSA tended to increase, likely due to edema in the operated leg (P = .10). CONCLUSIONS: Six days of hospitalization following elective total hip arthroplasty leads to substantial leg muscle atrophy in older patients. Effective intervention strategies are warranted to prevent the loss of muscle mass induced by short periods of muscle disuse during hospitalization.