Inhaling salbutamol may decrease time to exhaustion in some contexts of heavy endurance performances.

PURPOSE: To study the effect of inhaling a beta-agonist (salbutamol) compared to placebo on skiing and cycling performance in well-trained elite athletes. METHODS: Three different exercise protocols were used, all with a cross-over double blind placebo-controlled design. Participants inhaled 800 µg salbutamol or a placebo prior to the test, which was repeated on a following day with the participants inhaling the other substance. Fifteen junior elite skiers performed four free-style high intensity sprints (1100 m/work time 3.5-4.5 min). Twelve elite cyclists carried out a short cycling protocol, starting with two 5 min submaximal workloads followed by a maximal intermittent performance test to exhaustion. Another 12 elite cyclists performed the maximal intermittent performance test to exhaustion after a 150 min long submaximal cycling protocol. RESULTS: Group mean time for the ski sprints increased, with no difference between treatment groups. In the short cycling protocol time to exhaustion was 9.1% (95% CI 52-161) lower after inhaling salbutamol compared to placebo and in the long cycling protocol time to exhaustion was 9.1% (95% CI - 121-267) lower after inhaling salbutamol compared to placebo. Blood lactate, heart rate and ventilation increased during submaximal exercise with salbutamol compared to placebo in the short cycling protocol (p < .05). CONCLUSION: This study could not confirm any positive performance effects from inhaling 800 µg salbutamol compared to placebo in skiing and high-intensity intermittent cycling performance. Instead, time to exhaustion in the maximal intermittent performance test was lower in both cycling protocols.HighlightsThere was no difference in performance time between salbutamol and placebo treatment in real-life applicable repeated ski sprints.Time to exhaustion in the maximal intermittent performance test was 9.1% lower after inhaling salbutamol compared to placebo, both when performed after 10 and 150 min of submaximal cycling.

Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.

Background: Hyperoxia (HYPER) increases O2 carrying capacity resulting in a higher O2 delivery to the working muscles during exercise. Several lines of evidence indicate that lactate metabolism, power output, and endurance are improved by HYPER compared to normoxia (NORM). Since HYPER enables a higher exercise power output compared to NORM and considering the O2 delivery limitation at exercise intensities near to maximum, we hypothesized that hyperoxic-supplemented high-intensity interval training (HIIT) would upregulate muscle mitochondrial oxidative capacity and enhance endurance cycling performance compared to training in normoxia. Methods: 23 trained cyclists, age 35.3 ± 6.4 years, body mass 75.2 ± 9.6 kg, height 179.8 ± 7.9 m, and VO2max 4.5 ± 0.7 L min-1 performed 6 weeks polarized and periodized endurance training on a cycle ergometer consisting of supervised HIIT sessions 3 days/week and additional low-intensity training 2 days/week. Participants were randomly assigned to either HYPER (FIO2 0.30; n = 12) or NORM (FIO2 0.21; n = 11) breathing condition during HIIT. Mitochondrial respiration in permeabilized fibers and isolated mitochondria together with maximal and submaximal VO2, hematological parameters, and self-paced endurance cycling performance were tested pre- and posttraining intervention. Results: Hyperoxic training led to a small, non-significant change in performance compared to normoxic training (HYPER 6.0 ± 3.7%, NORM 2.4 ± 5.0%; p = 0.073, ES = 0.32). This small, beneficial effect on the self-paced endurance cycling performance was not explained by the change in VO2max (HYPER 1.1 ± 3.8%, NORM 0.0 ± 3.7%; p = 0.55, ES = 0.08), blood volume and hemoglobin mass, mitochondrial oxidative phosphorylation capacity (permeabilized fibers: HYPER 27.3 ± 46.0%, NORM 16.5 ± 49.1%; p = 0.37, ES = 3.24 and in isolated mitochondria: HYPER 26.1 ± 80.1%, NORM 15.9 ± 73.3%; p = 0.66, ES = 0.51), or markers of mitochondrial content which were similar between groups post intervention. Conclusions: This study showed that 6 weeks hyperoxic-supplemented HIIT led to marginal gain in cycle performance in already trained cyclists without change in VO2max, blood volume, hemoglobin mass, mitochondrial oxidative phosphorylation capacity, or exercise efficiency. The underlying mechanisms for the potentially meaningful performance effects of hyperoxia training remain unexplained and may raise ethical questions for elite sport.

Muscle mass and inspired oxygen influence oxygen extraction at maximal exercise: Role of mitochondrial oxygen affinity.

AIM: We examined the Fick components together with mitochondrial O2 affinity (p50mito ) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER). METHODS: Seven individuals performed 2 incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and 2 on a 1-legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP-stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibres and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery. RESULTS: The ex vivo p50mito increased from 0.06 ± 0.02 to 0.17 ± 0.04 kPa with varying substrate supply and O2 flux rates from 9.84 ± 2.91 to 16.34 ± 4.07 pmol O2 ·s-1 ·µg-1 respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time. CONCLUSION: O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise.

Hyperoxia for performance and training.

Recent technological developments have made it possible to use hyperoxia as an enhancement aid during training. Athletes wearing a mask can breathe a higher fraction of oxygen from a stationary or portable apparatus while exercising. A large body of evidence indicates that the oxygen transport capacity, lactate metabolism, power output and work tolerance (endurance) are improved when breathing hyperoxia. The physiological mechanisms underlying these performance improvements, although still not fully elucidated, are based on higher oxygen delivery and reduced central fatigue. Although much is known about the acute effects of hyperoxia, the effect of hyperoxic-supplemented endurance training on performance and the mechanisms beneath training adaptations are not very well understood, especially in well-trained endurance athletes. The few studies on the physiological effects of hyperoxia training have been conducted with conflicting results, discussed in this paper. Potential detrimental effects have not yet been shown experimentally and warrant further investigation.

Association of perceived physical health and physical fitness in two Swedish national samples from 1990 and 2015.

Perceived health and physical fitness have been shown to correlate, and low levels of either variable increase the risk for future illness and mortality. However, risk factors and their interrelationship may vary between societies and over time. In this study, the associations of physical fitness and perceived health were therefore assessed in two Swedish national samples 25 years apart. Perceived physical health, dichotomized as "good" or "bad," maximal oxygen uptake (VO2 max), counter movement jump (CMJ), balance (one-legged 60 second stance), and self-reported demographics and lifestyle were recorded in two cross-sectional samples (sample size, number of eligible participants) of Swedish adults, aged 20-65 years, in 1990-1991 (2203, 1365), and 2013-2015 (3357, 422). The odds for good perceived physical health increased by 5% per mL·kg-1 ·min-1 of VO2 max, 3% per cm CMJ height, and decreased by 4% per 1 time of overbalancing, in both samples. Mutually adjusted regression models showed that perceived physical health was best predicted by VO2 max and chronic illness in 1990 and by age, BMI, and educational level in 2015. CONCLUSION: Perceived physical health was related to physical fitness in two samples of Swedish adults from 1990 and 2015. However, multivariate and mutually adjusted models indicate that the most important covariates of perceived physical health may have changed from VO2 max and chronic illness in 1990, to age, BMI, and educational level in 2015.

The muscle biopsy technique. Historical and methodological considerations.

The muscle biopsy method is an important tool for clinical and scientific work. In this study, the two most used instruments, the Bergström needle and the Well-Blakesley conchotome, are described. The technique of using those instruments, risks, and other considerations are discussed. Finally, a few consequences and the error of the method for determining muscle fiber type, fiber area, substrates, and metabolites are presented.

Strength training improves muscle aerobic capacity and glucose tolerance in elderly.

The primary aim of this study was to investigate the effect of short-term resistance training (RET) on mitochondrial protein content and glucose tolerance in elderly. Elderly women and men (age 71 ± 1, mean ± SEM) were assigned to a group performing 8 weeks of resistance training (RET, n = 12) or no training (CON, n = 9). The RET group increased in (i) knee extensor strength (concentric +11 ± 3%, eccentric +8 ± 3% and static +12 ± 3%), (ii) initial (0-30 ms) rate of force development (+52 ± 26%) and (iii) contents of proteins related to signaling of muscle protein synthesis (Akt +69 ± 20 and mammalian target of rapamycin +69 ± 32%). Muscle fiber type composition changed to a more oxidative profile in RET with increased amount of type IIa fibers (+26.9 ± 6.8%) and a trend for decreased amount of type IIx fibers (-16.4 ± 18.2%, P = 0.068). Mitochondrial proteins (OXPHOS complex II, IV, and citrate synthase) increased in RET by +30 ± 11%, +99 ± 31% and +29 ± 8%, respectively. RET resulted in improved oral glucose tolerance measured as reduced area under curve for glucose (-21 ± 26%) and reduced plasma glucose 2 h post-glucose intake (-14 ± 5%). In CON parameters were unchanged or impaired. In conclusion, short-term resistance training in elderly not only improves muscular strength, but results in robust increases in several parameters related to muscle aerobic capacity.

A new submaximal cycle ergometer test for prediction of VO2max.

Maximal oxygen uptake (VO2max) is an important, independent predictor of cardiovascular health and mortality. Despite this, it is rarely measured in clinical practice. The aim of this study was to create and evaluate a submaximal cycle ergometry test based on change in heart rate (HR) between a lower standard work rate and an individually chosen higher work rate. In a mixed population (n = 143) with regard to sex (55% women), age (21-65 years), and activity status (inactive to highly active), a model included change in HR per unit change in power, sex, and age for the best estimate of VO2max. The association between estimated and observed VO2max for the mixed sample was r = 0.91, standard error of estimate = 0.302 L/min, and mean measured VO2max = 3.23 L/min. The corresponding coefficient of variation was 9.3%, a significantly improved precision compared with one of the most commonly used submaximal exercise tests, the Åstrand test, which in the present study was estimated to be 18.1%. Test-retest reliability analysis over 1 week revealed no mean difference in the estimated VO2max (-0.02 L/min, 95% confidence interval: -0.07-0.03). The new test is low-risk, easily administered, and valid for a wide capacity range, and is therefore suitable in situations as health evaluations in the general population.

What limits [V(·)]O(2max)? A symposium held at the BASES Conference, 6 September 2010.

Three modern views about the factors limiting oxygen uptake in healthy humans are set against the original (early 1920s) concept of A. V. Hill and colleagues. The majority view for most of the intervening time has been that cardiac output is the essential limiting function. Among recent research in support of this contention is that, in quadrupeds, pericardiectomy, which allows greater diastolic filling, elevates maximum oxygen uptake; however, the relevance to bipedal exercise can be questioned. In any case, algebraic analyses of model systems indicate that all identifiable stages on the oxygen transport pathway, from pulmonary diffusion to oxidative phosphorylation in skeletal muscle mitochondria, materially influence maximum uptake. Thus, if a high cardiac output is to be of benefit, all the other steps must function better too. Nevertheless, these two viewpoints concur that the limit to maximum oxygen uptake is somatic. In contrast, there are strong indications that at altitudes where oxygen availability is about half that at sea level, cerebral oxygenation is a limiting factor, and some recent experiments raise the possibility that it might be a substantial influence at sea level also. Clearly, consensus cannot yet be reached on the question posed in the title.

Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects.

AIM: The major aim of this study was to determine the fractional rate of protein synthesis (FSR) during the early period of recovery after intensive aerobic exercise in the absence of nutritional supplementation. METHODS: Sixteen male subjects performed one-legged cycling exercise for 1 h at approx. 65-70% of their one-legged maximal oxygen uptake. Using the stable isotope technique, the FSR in the vastus lateralis of both legs were determined during two periods, 0-90 min (n = 8) and 90-180 min (n = 8) after exercise. Biopsies were taken from both exercising and resting muscle before exercise, immediately after and following 90 or 180 min of recovery. RESULTS: During the initial 90 min of recovery, FSR in the exercising muscle tended to be higher than in the resting muscle (1.57 ± 0.12 vs. 1.44 ± 0.07% 24 h(-1); P = 0.1) and was significantly higher during the period 90-180 min after exercise (1.74 ± 0.14 vs. 1.43 ± 0.12% 24 h(-1) ; P < 0.05). Exercise induced a 60% increase (P < 0.05) in phosphorylation of mTOR and a fivefold increase (P < 0.05) in Thr(389) phosphorylation of p70S6 kinase as well as a 30% reduction (P < 0.05) in phosphorylation of eEF2. Phosphorylation of AMP-activated protein kinase was enhanced by 40% (P < 0.05) after exercise, but no significant effect on phosphorylation of Akt, or eIF2Bε was observed immediately after exercise. CONCLUSION: These findings indicate that during the first 3 h of recovery after intensive endurance exercise FSR gradually increases. Moreover, a stimulation of the mTOR-signalling pathway may be at least partially responsible for this elevated protein synthesis.

Deltoid muscle fiber characteristics in adolescent and adult wrestlers.

AIM: The aim of the present study was to examine the adaptation of myosin heavy chain (MHC) isoforms, capillary density and fiber cross sectional area (CSA) of deltoid muscle in adolescent and adult elite Greco-Roman wrestlers. METHODS: Eighteen Greco-Roman wrestlers were divided into two groups: adolescents included 10 athletes (group A) between 14-18 years of age (15.4+/-1.3 yrs) and adults included 8 athletes (group B) between 20-27 years (23.5+/-2.6 yrs). Histochemical analyses were used to determine the muscle fiber type distribution and the muscle fiber cross sectional area. MHC isoform composition was determined with protein electrophoresis, while capillary density (capillary to fiber ratio and capillaries per mm2) analysis was performed with a-amylase Periodic and Schiff staining. RESULTS: Adolescents demonstrated a significantly higher percentage of type I fibers (P<0.05) and type I fiber area (P<0.05) compared to the adults. The percentage of type IIa fiber area were significantly higher in adult wrestlers (P<0.05). MHC I isoforms was significantly higher in adolescents (P<0.05), whereas the MHC isoforms of IIa and IIx did not differ between groups. The capillary density (mm2) were significantly higher (P<0.05) in adolescents compared to adults. CONCLUSION: Our findings suggest that the observed muscle fiber profile in the deltoid muscle of wrestlers may represent an adaptation based on the mechanical and biochemical demands of the long-term training. Such adaptations are linked to the specific characteristics of the training program, the level and the previous training experience of the wrestlers.

Deltoid muscle characteristics in wrestlers.

The purpose of the present study was to investigate the deltoid muscle characteristics of wrestlers. Nine Greco-Roman competitive male wrestlers (mean age 20.1+/-2.7 yrs, height 175+/-0.6 cm, weight 83.2+/-12.5 kg, years of training 7.6+/-2.7 yrs) participated in this study. Six male healthy sedentary students (mean age 21.2+/-0.9 yrs, height 180+/-0.3 cm, weight 80.1+/-9.4 kg) served as controls. Muscle fibre distribution, cross-sectional area (CSA), as well as satellite cells, myonuclei and capillary density per muscle fibre area were determined by immunohistochemistry. Myosin heavy chain MHC isoform composition of single fibres was determined with protein electrophoresis. Immunohistochemical analysis showed that muscle fibre distribution of the MHC I and IIA were significantly higher in wrestlers than in controls (p<0.05). Electrophoretic analysis of single fibres revealed a significantly higher proportion of fibres containing MHC I and IIC in wrestlers (p<0.05). The mean CSA of type IIA fibres and the number of myonuclei per type II was significantly higher in wrestlers (p<0.05). We also found that the number of satellite cells was 2.5 fold higher in wrestlers than in the control group. This study suggests that the observed muscle fibre profile in the deltoid of wrestlers may represent an adaptation based on the specific mechanical and biochemical demands of the long-term training in Greco-Roman wrestling.

Reversed drift in heart rate but increased oxygen uptake at fixed work rate during 24 h ultra-endurance exercise.

In this paper we report a reversed drift in heart rate (HR) but increased oxygen uptake (VO(2)) during ultra-endurance exercise. Nine well-trained male athletes performed 24-h exercise in a controlled laboratory setting, with alternating blocks of kayaking, running and cycling. Each block included 110 min of exercise and 10 min of rest, with an average work intensity of approximately 55% of respective VO(2peak). Blood samples were taken and HR and VO(2) measured every 6th hour during steady-state cycling at fixed work rate. As assumed HR was increased at 6 h by 15 +/- 6 beats/min compared with initial level (0 h). Thereafter the drift did not progress continuously, but instead unexpectedly returned toward initial values, although the plasma levels of catecholamines increased continuously during exercise. VO(2) was increased by 0.22 +/- 0.15 L/min (10%) at 6 h and 0.37 +/- 0.18 L/min (17%) at 12 h compared with 0 h, and thereafter remained stable. This implies an increased oxygen pulse (VO(2)/HR) by approximately 10% at the last half of the 24-h exercise compared with 0 h. Consequently, sole use of HR would give inaccurate estimates of exercise intensity and energy expenditure during endurance exercise lasting more than 6 h, and different patterns of cardiovascular drift need to be taken into account.

Fitness and abdominal obesity are independently associated with cardiovascular risk.

OBJECTIVES: To examine the relationship between cardiovascular fitness (VO(2)max) and abdominal obesity (waist circumference) and individual cardiovascular disease (CVD) risk factors, as well as a clustered risk factor profile, and to study the impact of gender, age and smoking on these relationships. DESIGN: Cross-sectional. SETTING: Astrand Laboratory of Work Physiology, Swedish School of Sport and Health Sciences, Stockholm, Sweden. SUBJECTS: Men (n = 781) and women (n = 890) from two random population-based samples of Swedish women and men aged 20 to 65 years. MAIN OUTCOMES: Odds ratios. RESULTS: Each unit of higher fitness was associated with a decrease in all individual risk factors ranging from 2% to 4% independent of waist circumference, each unit of higher waist circumference was associated with an increased risk ranging from 2% to 5% independent of fitness. For clustering of three or more of the risk factors, each unit of fitness was associated with a 5% decrease in risk and each unit of waist circumference with a 5% increase in risk. The clustered risk was higher in unfit participants who were older or smoked daily, regardless of waist circumference. Obese participants were at higher risk if they were men or older, regardless of fitness level. However, neither a higher fitness level nor lean status reduced the risk associated with smoking. CONCLUSIONS: Higher fitness and lower waist circumference are each independently associated to a similar extent with a lower CVD risk. Simultaneous evaluation of both fitness and abdominal obesity status in clinical practice is important.

Lack of sex differences in the IGF-IGFBP response to ultra endurance exercise.

The insulin-like growth factor (IGF)-IGF binding proteins (BP) and the pituitary-gonadal axes were investigated during ultra endurance exercise in 16 endurance-trained athletes (seven women). Median duration of the race was 6.3 days. Although food and drink were ad libitum, energy balance was negative. Blood samples were drawn before (PRE), at the end of (END) and 24 h after (POST24h) the race. Serum concentrations of total IGF-I (t-IGF-I) and free IGF-I (f-IGF-I) decreased by 33 (SD 38)% and 54 (19)%, respectively. The decrease in t-IGF-I appeared to be associated to the total energy deficit during the race. At END, the IGFBP-3 fragmentation and IGFBP-1 were increased but these changes did not predict changes in f-IGF-I. An increase in POST24h IGFBP-2 levels in women was the only sex difference. Testosterone was decreased by 67 (12)% in the men and estradiol became undetectable in the women without any detectable increase in LH and/or FSH. In conclusion ultra endurance exercise results in similar IGF-IGFBP responses in men and women reflecting a catabolic state. IGFBP-2 was the only exception, with increased levels in women after exercise. A concomitant decrease in gonadal hormones was not related to endocrine changes in the IGF-IGFBP axis but may be related to local changes in IGF-I expression.

Fatigue and illness in athletes.

Adequate nutrition before, during, and after training and competition is a key element to maintaining health. During both sprint and endurance exercise, the availability of glycogen is fundamental to performance and any deficit will lead to early fatigue. In addition, strategies to offset the negative effects of the products of metabolism are presented. Although nutritional strategies can attenuate the immunosuppressive effects of exercise, there remains a period of susceptibility to infection after a hard exercise session and when this is repeated without sufficient recovery an athlete can enter a period of "overtraining" during which performance deteriorates. The aetiology and identification of this state is not clear and some current ideas are discussed. Finally, gastrointestinal problems during running can negate any training benefits and we propose some suggestions to reduce this problem.

Effects of dietary nitrate on oxygen cost during exercise.

AIM: Nitric oxide (NO), synthesized from l-arginine by NO synthases, plays a role in adaptation to physical exercise by modulating blood flow, muscular contraction and glucose uptake and in the control of cellular respiration. Recent studies show that NO can be formed in vivo also from the reduction of inorganic nitrate (NO(3) (-)) and nitrite (NO(2) (-)). The diet constitutes a major source of nitrate, and vegetables are particularly rich in this anion. The aim of this study was to investigate if dietary nitrate had any effect on metabolic and circulatory parameters during exercise. METHOD: In a randomized double-blind placebo-controlled crossover study, we tested the effect of dietary nitrate on physiological and metabolic parameters during exercise. Nine healthy young well-trained men performed submaximal and maximal work tests on a cycle ergometer after two separate 3-day periods of dietary supplementation with sodium nitrate (0.1 mmol kg(-1) day-1) or an equal amount of sodium chloride (placebo). RESULTS: The oxygen cost at submaximal exercise was reduced after nitrate supplementation compared with placebo. On an average Vo(2) decreased from 2.98 +/- 0.57 during CON to 2.82 +/- 0.58 L min(-1) during NIT (P < 0.02) over the four lowest submaximal work rates. Gross efficiency increased from 19.7 +/- 1.6 during CON to 21.1 +/- 1.3% during NIT (P < 0.01) over the four lowest work rates. There was no difference in heart rate, lactate [Hla], ventilation (VE), VE/Vo(2) or respiratory exchange ratio between nitrate and placebo during any of the submaximal work rates. CONCLUSION: We conclude that dietary nitrate supplementation, in an amount achievable through a diet rich in vegetables, results in a lower oxygen demand during submaximal work. This highly surprising effect occurred without an accompanying increase in lactate concentration, indicating that the energy production had become more efficient. The mechanism of action needs to be clarified but a likely first step is the in vivo reduction of dietary nitrate into bioactive nitrogen oxides including nitrite and NO.

Changes in signalling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise.

AIM: Exercise induced alterations in the rate of muscle protein synthesis may be related to activity changes in signalling pathways involved in protein synthesis. The aim of the present study was to investigate whether such changes in enzyme phosphorylation occur after endurance exercise. METHODS: Six male subjects performed ergometer cycling exercise for 1 h at 75% of the maximal oxygen uptake. Muscle biopsy samples from the vastus lateralis were taken before, immediately after, 30 min, 1 h, 2 h and 3 h after exercise for the determination of protein kinase B (PKB/Akt), mammalian target of rapamycin (mTOR), glycogen synthase 3 kinase (GSK-3), p70S6 kinase (p70(S6k)) and eukaryotic elongation factor 2 (eEF2) phosphorylation. RESULTS: The phosphorylation of Akt was unchanged directly after exercise, but two- to fourfold increased 1 and 2 h after the exercise, whereas GSK-3alpha and beta phosphorylation were two- to fourfold elevated throughout most of the 3-h recovery period. Phosphorylation of mTOR was elevated threefold directly after, 30 min and 2 h after exercise and eEF2 phosphorylation was decreased by 35-75% from 30 min to 3 h-recovery. Exercise led to a five- to eightfold increase in Ser(424)/Thr(421) phosphorylation of p70(S6k) up to 30 min after exercise, but no change in Thr(389) phosphorylation. CONCLUSIONS: The marked decrease in eEF2 phosphorylation suggests an activation of translation elongation and possibly protein synthesis in the recovery period after sustained endurance exercise. The lack of p70(S6k) activation suggests that translation initiation is activated via alternative pathways, possibly via the activation of eukaryotic initiating factor 2B.