Effects of carbohydrate availability on cycling endurance at the maximal lactate steady state.

The impacts of carbohydrate (CHO) availability on time to task failure (TTF) and physiological responses to exercise at the maximal lactate steady state (MLSS) have not been studied. Ten participants (3 females, 7 males) completed this double-blinded, placebo-controlled study that involved a ramp incremental test, MLSS determination, and four TTF trials at MLSS, all performed on a cycle ergometer. With the use of a combination of nutritional (CHO, 7 g/kg, and placebo, PLA, 0 g/kg drinks) and exercise interventions [no exercise (REST) and glycogen-reducing exercise (EX)], the four conditions were expected to differ in preexercise CHO availability (RESTCHO > RESTPLA > EXCHO > EXPLA). TTF at MLSS was not improved by CHO loading, as RESTCHO (57.1 [16.6] min) and RESTPLA (57.1 [15.6] min) were not different (P = 1.00); however, TTF was ∼50% shorter in EX conditions compared with REST conditions on average (P < 0.05), with EXCHO (39.1 [9.2] min) ∼90% longer than EXPLA (20.6 [6.9] min; P < 0.001). There were effects of condition for all perceptual and cardiometabolic variables when compared at isotime (P < 0.05) and task failure (TF; P < 0.05), except for ventilation, perceptual responses, and neuromuscular function measures, which were not different at TF (P > 0.05). Blood lactate concentration was stable in all conditions for participants who completed 30 min of exercise. These findings indicate that TTF at MLSS is not enhanced by preexercise CHO supplementation, but recent intense exercise decreases TTF at MLSS even with CHO supplementation. Extreme fluctuations in diet and strenuous exercise that reduce CHO availability should be avoided before MLSS determination.NEW & NOTEWORTHY Carbohydrate (CHO) loading did not increase participants' ability to cycle at their maximal lactate steady state (MLSS); however, performing a glycogen depletion task the evening before cycling at MLSS reduced the time to task failure, even when paired with a high dose of CHO. These diet and exercise interventions influenced blood lactate concentration ([BLa]) but not the stability of [BLa]. Activities that reduce CHO availability should be avoided before MLSS determination.

Contraction intensity affects NIRS-derived skeletal muscle oxidative capacity but not its relationships to mitochondrial protein content or aerobic fitness.

To further refine the near-infrared spectroscopy (NIRS)-derived measure of skeletal muscle oxidative capacity in humans, we sought to determine whether the exercise stimulus intensity affected the τ value and/or influenced the magnitude of correlations with in vitro measures of mitochondrial content and in vivo indices of exercise performance. Males (n = 12) and females (n = 12), matched for maximal aerobic fitness per fat-free mass, completed NIRS-derived skeletal muscle oxidative capacity tests for the vastus lateralis following repeated contractions at 40% (τ40) and 100% (τ100) of maximum voluntary contraction, underwent a skeletal muscle biopsy of the same muscle, and performed multiple intermittent isometric knee extension tests to task failure to establish critical torque (CT). The value of τ100 (34.4 ± 7.0 s) was greater than τ40 (24.2 ± 6.9 s, P < 0.001), but the values were correlated (r = 0.688; P < 0.001). The values of τ40 (r = -0.692, P < 0.001) and τ100 (r = -0.488, P = 0.016) correlated with myosin heavy chain I percentage and several markers of mitochondrial content, including COX II protein content in whole muscle (τ40: r = -0.547, P = 0.006; τ100: r = -0.466, P = 0.022), type I pooled fibers (τ40: r = -0.547, P = 0.006; τ100: r = -0.547, P = 0.006), and type II pooled fibers (τ40: r = -0.516, P = 0.009; τ100: r = -0.635, P = 0.001). The value of τ40 (r = -0.702, P < 0.001), but not τ100 (r = -0.378, P = 0.083) correlated with critical torque (CT); however, neither value correlated with W' (τ40: r = 0.071, P = 0.753; τ100: r = 0.054, P = 0.812). Overall, the NIRS method of assessing skeletal muscle oxidative capacity is sensitive to the intensity of skeletal muscle contraction but maintains relationships to whole body fitness, isolated limb critical intensity, and mitochondrial content regardless of intensity.NEW & NOTEWORTHY Skeletal muscle oxidative capacity measured using near-infrared spectroscopy (NIRS) was lower following high-intensity compared with low-intensity isometric knee extension contractions. At both intensities, skeletal muscle oxidative capacity was correlated with protein markers of mitochondrial content (in whole muscle and pooled type I and type II muscle fibers) and critical torque. These findings highlight the importance of standardizing contraction intensity while using the NIRS method with isometric contractions and further demonstrate its validity.

The influence of skeletal muscle mitochondria and sex on critical torque and performance fatiguability in humans.

Critical torque (CT) represents the highest oxidative steady state for intermittent knee extensor exercise, but the extent to which it is influenced by skeletal muscle mitochondria and sex is unclear. Vastus lateralis muscle biopsy samples were collected from 12 females and 12 males -matched for relative maximal oxygen uptake normalized to fat-free mass (FFM) (F: 57.3 (7.5) ml (kg FFM)-1  min-1 ; M: 56.8 (7.6) ml (kg FFM)-1  min-1 ; P = 0.856) - prior to CT determination and performance fatiguability trials. Males had a lower proportion of myosin heavy chain (MHC) I isoform (40.6 (18.4)%) compared to females (59.5 (18.9)%; P = 0.021), but MHC IIa and IIx isoform distributions and protein markers of mitochondrial content were not different between sexes (P > 0.05). When normalized to maximum voluntary contraction (MVC), the relative CT (F: 42.9 (8.3)%; M: 37.9 (9.0)%; P = 0.172) and curvature constant, W' (F: 26.6 (11.0) N m s (N m)-1 ; M: 26.4 (6.5) N m s (N m)-1 ; P = 0.962) were not significantly different between sexes. All protein biomarkers of skeletal muscle mitochondrial content, as well as the proportion of MHC I isoform, positively correlated with relative CT (0.48 < r < 0.70; P < 0.05), and the proportion of MHC IIx isoform correlated positively with relative W' (r = 0.57; P = 0.007). Indices of performance fatiguability were not different between males and females for MVC- and CT-controlled trials (P > 0.05). Greater mitochondrial protein abundance was associated with attenuated declines in potentiated twitch torque for exercise at 60% MVC (P < 0.05); however, the influence of mitochondrial protein abundance on performance fatiguability was reduced when exercise was prescribed relative to CT. Whether these findings translate to whole-body exercise requires additional research. KEY POINTS: The quadriceps critical torque represents the highest intensity of intermittent knee extensor exercise for which an oxidative steady state is attainable, but its relationship with skeletal muscle mitochondrial protein abundance is unknown. Matching males and females for maximal oxygen uptake relative to fat-free mass facilitates investigations of sex differences in exercise physiology, but studies that have compared critical torque and performance fatiguability during intermittent knee extensor exercise have not ensured equal aerobic fitness between sexes. Skeletal muscle mitochondrial protein abundance was correlated with critical torque and fatigue resistance for exercise prescribed relative to maximum voluntary contraction but not for exercise performed relative to the critical torque. Differences between sexes in critical torque, skeletal muscle mitochondrial protein abundance and performance fatiguability were not statistically significant. Our results suggest that skeletal muscle mitochondrial protein abundance may contribute to fatigue resistance by influencing the critical intensity of exercise.

Multiparametric cytotoxicity assessment: the effect of gold nanoparticle ligand functionalization on SKOV3 ovarian carcinoma cell death.

Gold nanoparticles (AuNP) are promising anti-cancer agents because of their modifiable properties and high biocompatibility. This study used multiple parallel analyses to investigate the cytotoxic properties of 5 nm AuNP conjugated to four different ligands with distinct surface chemistry: polyethylene glycol (PEG), trimethylammonium bromide (TMAB), 4-dimethylaminopyridine (DMAP), and carboxyl (COOH). We used a range of biochemical and high-content microscopy methods to evaluate the metabolic function, oxidative stress, cell health, cell viability, and cell morphology in SKOV3 ovarian cancer cells. Each AuNP displayed a distinct cytotoxicity profile. All AuNP species assessed exhibited signs of dose-dependent cytotoxicity when morphology, clonogenic survival, lysosomal uptake, or cell number were measured as the marker of toxicity. All particles except for AuNP-COOH increased SKOV3 apoptosis. In contrast, AuNP-TMAB was the only particle that did not alter the metabolic function or induce significant signs of oxidative stress. These results demonstrate that AuNP surface chemistry impacts the magnitude and mechanism of SKOV3 cell death. Together, these findings reinforce the important role for multiparametric cytotoxicity characterization when considering the utility of novel particles and surface chemistries.