Christina Karatzaferi

Combination of Exercise Training and Dopamine Agonists in Patients with RLS on Dialysis: A Randomized, Double-Blind Placebo-Controlled Study.

Both exercise training and treatment with dopamine agonists (DA) have been used with success for the amelioration of uremic restless legs syndrome (RLS) symptoms. However, no data are available combining those two approaches. The aim of the current randomized, double-blind, placebo-controlled study was to investigate the effects of a 6 month intradialytic exercise training in combination with a low dose of DA in patients suffering from uremic RLS symptoms. Fourteen stable patients with RLS on hemodialysis were randomly assigned to the exercise training plus DA group and the exercise training plus placebo group. Both combinations were found to equally reduce uremic RLS symptoms by approximately 60%. The combination of low dose of DA with aerobic exercise training could be considered an alternative approach to high DA dosage regimes in reducing RLS symptoms’ severity.

Higher insulin sensitivity in EDL muscle of rats fed a low-protein, high-carbohydrate diet inhibits the caspase-3 and ubiquitin-proteasome proteolytic systems but does not increase protein synthesis

Compared with the extensor digitorum longus (EDL) muscle of control rats (C), the EDL muscle of rats fed a low-protein, high-carbohydrate diet (LPHC) showed a 36% reduction in mass. Muscle mass is determined by the balance between protein synthesis and proteolysis; thus, the aim of this work was to evaluate the components involved in these processes. Compared with the muscle from C rats, the EDL muscle from LPHC diet-fed rats showed a reduction (34%) in the in vitro basal protein synthesis and a 22% reduction in the in vitro basal proteolysis suggesting that the reduction in the mass can be associated with a change in the rate of the two processes. Soon after euthanasia, in the EDL muscles of the rats fed the LPHC diet for 15days, the activity of caspase-3 and that of components of the ubiquitin-proteasome system (atrogin-1 content and chymotrypsin-like activity) were decreased. The phosphorylation of p70(S6K) and 4E-BP1, proteins involved in protein synthesis, was also decreased. We observed an increase in the insulin-stimulated protein content of p-Akt. Thus, the higher insulin sensitivity in the EDL muscle of LPHC rats seemed to contribute to the lower proteolysis in LPHC rats. However, even with the higher insulin sensitivity, the reduction in p-E4-BP1 and p70(S6K) indicates a reduction in protein synthesis, showing that factors other than insulin can have a greater effect on the control of protein synthesis.

How Can Physical Activity Referral Rates for Breast Cancer Patients be Increased

Exercise therapy is beneficial for cancer survivors’ biopsychosocial aspects of health (1–3); however, the rates of exercise referrals by the oncology providers (OPs) and supporting teams remain low, causing a paradox. We chose to address this issue in this opinion article. We discuss the possible barriers that make the OPs unable or reluctant to refer more patients to exercise therapy sessions and also briefly address issues of patients’ adherence. Finally, the available exercise therapy infrastructure is discussed as an additional barrier to the therapeutic benefits of exercise. Our rationale is based on the fact that physical activity (PA) can enable wide-reaching benefits for the recovery of cancer patients during and after cancer treatment (4–6). Moreover, and specifically for breast cancer survivors, the recent trials and a systematic review disproved the notion that arm exercise should be avoided (i.e., postoperative progressive arm resistance training does not precipitate or exacerbate lymphedema) (7–9). This further supports the beneficial effects of PA across a range of contexts. In the UK, 1.6 million cancer survivors out of a total of 2 million do not meet the minimum recommended PA guidelines for sustaining an independent and disability-free lifestyle (10). A single-blinded randomized control trial has shown that cancer survivors are more likely to become physically active if they are advised to do so by a health-care professional (11). This highlights the impact OPs have on patients’ life and survival, especially when the treatments involve a life-changing approach, such as increasing PA levels, commitment to exercise training, and adopting a healthier lifestyle. Based on our own knowledge on cancer care practices and on research experience in other patient populations (12), we hypothesized that the main reasons behind the exercise referral paradox for breast cancer survivors in England are (1) lack of time during a consultation to promote PA, (2) OPs and supporting team lack of current knowledge and awareness of the benefits of PA in cancer survivors’ biopsychosocial aspects of health, and (3) the lack of knowledge and confidence from the patients’ side to request an exercise referral from the OPs.

Modulators of actin-myosin dissociation: basis for muscle type functional differences during fatigue

The muscle types present with variable fatigue tolerance, in part due to the myosin isoform expressed. However, the critical steps that define “fatigability” in vivo of fast vs. slow myosin isoforms, at the molecular level, are not yet fully understood. We examined the modulation of the ATP-induced myosin subfragment 1 (S1) dissociation from pyrene-actin by inorganic phosphate (Pi), pH, and temperature using a specially modified stopped-flow system that allowed fast kinetics measurements at physiological temperature. We contrasted the properties of rabbit psoas (fast) and bovine masseter (slow) myosins (obtained from samples collected from New Zealand rabbits and from a licensed abattoir, respectively, according to institutional and national ethics permits). To identify ATP cycling biochemical intermediates, we assessed ATP binding to a preequilibrated mixture of actomyosin and variable [ADP], pH (pH 7 vs. pH 6.2), and Pi (zero, 15, or 30 added mM Pi) in a range of temperatures (5 to 45°C). Temperature and pH variations had little, if any, effect on the ADP dissociation constant (KADP) for fast S1, but for slow S1, KADP was weakened with increasing temperature or low pH. In the absence of ADP, the dissociation constant for phosphate (KPi) was weakened with increasing temperature for fast S1. In the presence of ADP, myosin type differences were revealed at the apparent phosphate affinity, depending on pH and temperature. Overall, the newly revealed kinetic differences between myosin types could help explain the in vivo observed muscle type functional differences at rest and during fatigue.