Search

Key points: Low‐volume high‐intensity exercise training promotes muscle mitochondrial adaptations that resemble those associated with high‐volume moderate‐intensity exercise training. These training‐induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whether metabolic stress is a key mediator of the acute molecular responses to high‐intensity exercise is still incompletely understood. Here we show that, by comparing different work‐matched low‐volume high‐intensity exercise protocols, more marked metabolic perturbations were associated with enhanced mitochondrial biogenesis‐related muscle mRNA responses. Furthermore, when compared with high‐volume moderate‐intensity exercise, only the low‐volume high‐intensity exercise eliciting severe metabolic stress compensated for reduced exercise volume in the induction of mitochondrial biogenic mRNA responses. The present results, besides improving our understanding of the mechanisms mediating exercise‐induced mitochondrial biogenesis, may have implications for applied and clinical research that adopts exercise as a means to increase muscle mitochondrial content and function in healthy or diseased individuals. Abstract: The aim of the present study was to examine the impact of exercise‐induced metabolic stress on regulation of the molecular responses promoting skeletal muscle mitochondrial biogenesis. Twelve endurance‐trained men performed three cycling exercise protocols characterized by different metabolic profiles in a randomized, counter‐balanced order. Specifically, two work‐matched low‐volume supramaximal‐intensity intermittent regimes, consisting of repeated‐sprint (RS) and speed endurance (SE) exercise, were employed and compared with a high‐volume continuous moderate‐intensity exercise (CM) protocol. Vastus lateralis muscle samples were obtained before, immediately after, and 3 h after exercise. SE produced the most marked metabolic perturbations as evidenced by the greatest changes in muscle lactate and pH, concomitantly with higher post‐exercise plasma adrenaline levels in comparison with RS and CM. Exercise‐induced phosphorylation of CaMKII and p38 MAPK was greater in SE than in RS and CM. The exercise‐induced PGC‐1α mRNA response was higher in SE and CM than in RS, with no difference between SE and CM. Muscle NRF‐2, TFAM, MFN2, DRP1 and SOD2 mRNA content was elevated to the same extent by SE and CM, while RS had no effect on these mRNAs. The exercise‐induced HSP72 mRNA response was larger in SE than in RS and CM. Thus, the present results suggest that, for a given exercise volume, the initial events associated with mitochondrial biogenesis are modulated by metabolic stress. In addition, high‐intensity exercise seems to compensate for reduced exercise volume in the induction of mitochondrial biogenic molecular responses only when the intense exercise elicits marked metabolic perturbations. [ABSTRACT FROM AUTHOR]

We compared the accuracy of 2 GPS systems with different sampling rates for the determination of distances covered at high-speed and metabolic power derived from a combination of running speed and acceleration. 8 participants performed 56 bouts of shuttle intermittent running wearing 2 portable GPS devices (SPI-Pro, GPS-5 Hz and MinimaxX, GPS-10 Hz). The GPS systems were compared with a radar system as a criterion measure. The variables investigated were: total distance (TD), high-speed distance (HSR>4.17 m•s-1), very high-speed distance (VHSR>5.56 m•s-1), mean power (Pmean), high metabolic power (HMP>20 W•kg-1) and very high metabolic power (VHMP>25 W•kg-1). GPS-5 Hz had low error for TD (2.8%) and Pmean (4.5%), while the errors for the other variables ranged from moderate to high (7.5-23.2%). GPS-10 Hz demonstrated a low error for TD (1.9%), HSR (4.7%), Pmean (2.4%) and HMP (4.5%), whereas the errors for VHSR (10.5%) and VHMP (6.2%) were moderate. In general, GPS accuracy increased with a higher sampling rate, but decreased with increasing speed of movement. Both systems could be used for calculating TD and Pmean, but they cannot be used interchangeably. Only GPS-10 Hz demonstrated a sufficient level of accuracy for quantifying distance covered at higher speeds or time spent at very high power. [ABSTRACT FROM AUTHOR]

Statins are the preferred class of drugs for treating patients with atherosclerosis and related coronary heart disease. Treatment with statins leads to significant low-density lipoprotein cholesterol (LDL-C) lowering, resulting in reductions in major coronary and vascular events. Statins are generally well tolerated and safe; however, their use is complicated by infrequent, but often serious, muscular adverse events. For many statins, both efficacy and risk of adverse muscle events can be influenced by membrane transporters, which are important determinants of statin disposition. Genetic polymorphisms and drug–drug interactions (DDIs) involving organic anion-transporting polypeptide 1B1 and breast cancer resistance protein have shown the capacity to reduce the activity of these transporters, resulting in changes in LDL-C lowering by statins, as well as changes in the frequency of adverse muscle events associated with their use. This review presents evidence for how reduced transporter activity impacts the safety and pharmacology of statins. It expands on the scope of other recent statin reviews by providing recommendations on in vitro evaluation of statin interaction potential, discussing how reduced transporter activity impacts statin management during drug development, and proposing ideas on how to evaluate the impact of DDI on statin efficacy during clinical trials. Furthermore, the potential clinical consequences of perturbing statin efficacy via DDI are discussed. [ABSTRACT FROM AUTHOR]

Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1-T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node was positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer. [ABSTRACT FROM AUTHOR]