Progressive Resistance Training and Cancer Testis (PROTRACT) - Efficacy of resistance training on muscle function, morphology and inflammatory profile in testicular cancer patients undergoing chemotherapy: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Standard treatment for patients with disseminated germ cell tumors is combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This treatment is highly effective, but the majority of patients experience severe adverse effects during treatment and are at risk of developing considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, and pulmonary toxicity. One neglected side effect is the significant muscular fatigue mentioned by many patients with testicular cancer both during and after treatment. Very limited information exists concerning the patho-physiological effects of antineoplastic agents on skeletal muscle. The primary aim of this study is to investigate the effects of BEP-treatment on the skeletal musculature in testicular cancer patients, and to examine whether the expected treatment-induced muscular deterioration can be attenuated or even reversed by high intensity progressive resistance training (HIPRT).</p> <p>Design/Methods</p> <p>The PROTRACT study is a randomized controlled trial in 30 testicular cancer patients undergoing three cycles of BEP chemotherapy. Participants will be randomized to either a 9-week HIPRT program (STR) initiated at the onset of treatment, or to standard care (UNT). 15 healthy matched control subjects (CON) will complete the same HIPRT program. All participants will take part in 3 assessment rounds (baseline, 9 wks, 21 wks) including muscle biopsies, maximum muscle strength tests, whole body DXA scan and blood samples. <it>Primary outcome</it>: mean fiber area and fiber type composition measured by histochemical analyses, satellite cells and levels of protein and mRNA expression of intracellular mediators of protein turnover. Secondary outcomes: maximum muscle strength and muscle power measured by maximum voluntary contraction and leg-extensor-power tests, body composition assessed by DXA scan, and systemic inflammation analyzed by circulating inflammatory markers, lipid and glucose metabolism in blood samples. Health related Quality of Life (QoL) will be assessed by validated questionnaires (EORTC QLQ-C30, SF-36).</p> <p>Discussion</p> <p>This study investigates the muscular effects of antineoplastic agents in testicular cancer patients, and furthermore evaluates whether HIPRT has a positive influence on side effects related to chemotherapy. A more extensive knowledge of the interaction between cytotoxic-induced physiological impairment and exercise-induced improvement is imperative for the future development of optimal rehabilitation programs for cancer patients.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN32132990">ISRCTN32132990</a>.</p

Key Components of Human Myofibre Denervation and Neuromuscular Junction Stability are Modulated by Age and Exercise

The decline in muscle mass and function with age is partly caused by a loss of muscle fibres through denervation. The purpose of this study was to investigate the potential of exercise to influence molecular targets involved in neuromuscular junction (NMJ) stability in healthy elderly individuals. Participants from two studies (one group of 12 young and 12 elderly females and another group of 25 elderly males) performed a unilateral bout of resistance exercise. Muscle biopsies were collected at 4.5 h and up to 7 days post exercise for tissue analysis and cell culture. Molecular targets related to denervation and NMJ stability were analysed by immunohistochemistry and real-time reverse transcription polymerase chain reaction. In addition to a greater presence of denervated fibres, the muscle samples and cultured myotubes from the elderly individuals displayed altered gene expression levels of acetylcholine receptor (AChR) subunits. A single bout of exercise induced general changes in AChR subunit gene expression within the biopsy sampling timeframe, suggesting a sustained plasticity of the NMJ in elderly individuals. These data support the role of exercise in maintaining NMJ stability, even in elderly inactive individuals. Furthermore, the cell culture findings suggest that the transcriptional capacity of satellite cells for AChR subunit genes is negatively affected by ageing

An Estimate of Plasma Volume Changes Following Moderate-High Intensity Running and Cycling Exercise and Adrenaline Infusion

Introduction: Plasma volume (PV) changes in response to physical activity, possibly as a consequence of adrenergic activation. We estimated changes in PV in response to common exercise modalities; cycling and running as well as adrenaline infusion and control at rest.Methods: On separate days, forty circulatory healthy subjects [aged 60 years (range: 42–75)] with knee osteoarthritis underwent moderate-high intensity cycling, running, and intravenous adrenaline infusion to mimic the circulatory response to exercise. Blood samples were obtained from peripheral veins taken at several pre-defined time points before, during, and after the interventions. PV changes were estimated using venous hemoglobin and the derived hematocrit. The temporal associations between PV and selected biomarkers were explored.Results: Changes in PV were observed during all four interventions, and the response to cycling and running was similar. Compared to rest, PV decreased by -14.3% (95% CI: -10.0 to -18.7) after cycling, -13.9% (95% CI: -10.9 to -17.0) after running, and -7.8% (95% CI: -4.2 to -11.5) after adrenaline infusion.Conclusion: PV decreased in response to moderate-high intensity running and cycling. Adrenaline infusion mimicked the PV change observed during exercise, suggesting a separate influence of autonomic control on blood volume homeostasis. In perspective, a temporal association between PV and biomarker dynamics suggests that consideration of PV changes could be relevant when reporting plasma/serum constituents measured during exercise, but more research is needed to confirm this

Evaluation of serum ARGS neoepitope as an osteoarthritis biomarker using a standardized model for exercise-induced cartilage extra cellular matrix turnover

Summary: Objective: To propose a standardized model for exercise-induced cartilage turnover and investigate residual levels and dynamics of biomarker serum ARGS (sARGS) in primary osteoarthritis (OA) patients and a supportive group of young healthy subjects. Method: The trial is a randomized, cross-over, exploratory study with interventions of exercise and inactivity. 20 subjects with knee OA, as well as 20 young healthy subjects (mean age 25.7 years (range; 19–30), 50% male), underwent cycling, running and resting interventions on separate days one week apart. Blood samples were taken at baseline, immediately, 1, 2, 3 and 24 h after activity start. sARGS was measured by sandwich ELISA. Results: Intraclass correlation between visits were 0.97 and 0.77 for the OA and healthy group, respectively. An acute drop in sARGS in response to high-intensity exercise was observed in both groups. Minute acute sARGS increase was observed in OA subjects in response to moderate intensity running and cycling, which normalized within 24 h. In healthy subjects an acute drop in sARGS was seen immediately after running, but not cycling, and no other changes were observed. A negative correlation between baseline Kellgren-Lawrence (KL) grade and baseline sARGS (r = −0.69, p = 0.002) in OA was found. A negative correlation between age and sARGS was found in healthy subjects (r = −0.67, p = <0.002). Conclusion: sARGS sensitivity to physical activity is considered low and sARGS is a reproducible and stable marker. Minute acute increases in sARGS were observed in the hours following moderate intensity exercise

Mutual stimulatory signaling between human myogenic cells and rat cerebellar neurons

Abstract Insight into the bidirectional signaling between primary human myogenic cells and neurons is lacking. For this purpose, human myogenic cells were derived from the semitendinosus and gracilis muscles of five healthy individuals and co‐cultured with cerebellar granule neurons from two litters of 7‐day‐old Wistar rat pups, in muscle medium or neural medium, alongside monocultures of myogenic cells or neurons. RT‐PCR was performed to determine human mRNA levels of GAPDH, Ki67, myogenin, and MUSK, and the acetylcholine receptor subtypes CHRNA1, CHRNB1, CHRNG, CHRND, and CHRNE, and rat mRNA levels of GAPDH, Fth1, Rack1, vimentin, Cdh13, and Ppp1r1a. Immunocytochemistry was used to evaluate neurite outgrowth (GAP43) in the presence and absence of myogenic cells. Co‐culture with primary neurons lead to higher myogenic cell gene expression levels of GAPDH, myogenin, MUSK, CHRNA1, CHRNG, and CHRND, compared to myogenic cells cultured alone. It appeared that neurons preferentially attached to myotubes and that neurite outgrowth was enhanced when neurons were cultured with myogenic cells compared to monoculture. In neural medium, rat mRNA levels of GAPDH, vimentin, Cdh13, and Ppp1r1a were greater in co‐culture, versus monoculture, whereas in muscle medium co‐culture lead to lower levels of Fth1, Rack1, vimentin, and Cdh13 than monoculture. These findings demonstrate mutually beneficial stimulatory signaling between rat cerebellar granule neurons and human myogenic cells, providing support for an active role for both the neuron and the muscle cell in stimulating neurite growth and myogenesis. Bidirectional muscle nerve signaling