Yuefei Liu

New aspects of the hormone and cytokine response to training

Exercise training is associated with peripheral-cellular and central-cerebral processes, hormonal-neuronal regulation and transmission mechanisms. During the acute training response, peripheral cellular mechanisms are mainly metabolostatic to achieve energy supply and involve associated cytokine and hormonal reactions. Glycogen deficiency is associated with increased expression of local cytokines (interleukin-6, IL-6), decreased expression of glucose transporters, increased cortisol and decreased insulin secretion and β-adrenergic stimulation. A nutrient-sensing signal of adipose tissue may be represented by leptin which, as for insulin, IL-6 and insulin-like growth-factor I (IGF-I), has profound effects on the hypothalamus and is involved in the metabolic hormonal regulation of exercise and training. Muscle damage and repair processes may involve the expression of inflammatory cytokines (e.g. tumour necrosis factor-α, TNF-α) and of stress proteins (e.g. heat shock protein 72). During overreaching and overtraining, a myopathy-like state is observed in skeletal muscle with depressed turnover of contractile proteins (e.g. in fast-type glycolytic fibres with a concomitant increase in slow type myosins). These alterations are influenced by exercise-induced hypercortisolism, and by decreased somatotropic hormones (e.g. IGF-I). The hypothalamus integrates various error signals (metabolic, hormonal, sensory afferents and central stimuli) and therefore pituitary releasing hormones represent the functional status of an athlete and long-term hypothalamic hormonal and sympathoadrenal downregulation are some of the prominent hormonal signs of prolonged overtraining and performance incompetence syndrome.

Response and function of skeletal muscle heat shock protein 70

In response to stress, cells produce a series of heat shock proteins (Hsps). One of the most prominent Hsps, is the 70 kDa Hsp (Hsp70). Hsp70 is a highly conserved and essential protein against stress. The skeletal muscle responds to a diverse group of stress signals namely, muscle contraction linked energy and milieu challenges, ischemia and exercise by producing Hsp70. The extent of this Hsp70 response in skeletal muscle depends on the type and intensity of the signal, and is characterized in a muscle fiber specific manner by a special time course. Hsp70 in the skeletal muscle is regulated at transcriptional, translational and posttranslational levels. Hsp70 serves as an indicator for cellular stress as a molecular chaperone, plays pivotal role in maintaining cellular homeostasis by preventing apoptosis, influences energy metabolism, facilitates cellular processes in terms of muscular adaptation and interacts with other signalling pathways. This review summarizes our current knowledge on the skeletal muscle Hsp70 response.

Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence for autocrine and paracrine actions

Interleukin-4 (IL-4) is an immunomodulatory cytokine, which can inhibit the growth of tumour cells. Pancreatic cancer cells and tissues express high levels of IL-4 receptors. The aim of this study was to characterise the effects of IL-4 on the growth and signalling pathways of pancreatic cancer cells. Cell growth was determined by cell counting and MTT assays in association with fluorescence-activated cell sorter analysis, IL-4 expression using ELISA and real-time PCR techniques, and signal transduction using immunoprecipitation or immunoblot analysis. We now report for the first time that IL-4 significantly enhanced the growth of five out of six cultured pancreatic cancer cell lines in a dose-dependent manner in association with an increased fraction of cells in S-phase. Surprisingly, all six cell lines expressed endogenous IL-4, and IL-4 was detectable in the supernatant. Incubating cells with neutralising IL-4 antibodies resulted in a significant inhibition of basal growth in three cell lines, including IL-4-unresponsive MIA PaCa-2 cells, which however expressed the highest endogenous IL-4 levels. Interleukin-4 enhanced activity of MAPK, Akt-1, and Stat3 in IL-4-responsive, but not in IL-4-unresponsive MIA PaCa-2 cells; however, IL-4 enhanced tyrosine phosphorylation of insulin receptor substrate-1 and -2 in all cell lines. Our results demonstrate for the first time that pancreatic cancer cells produce IL-4 and that IL-4 can act as a growth factor in pancreatic cancer cells. Together with the observation that neutralising IL-4 antibodies can inhibit the growth of these cells, our results suggest that IL-4 may act as an autocrine growth factor in pancreatic cancer cells and also give rise to the possibility that cancer-derived IL-4 may suppress cancer-directed immunosurveillance in vivo in addition to its growth-promoting effects, thereby facilitating pancreatic tumour growth and metastasis.

Response of growth and myogenic factors in human skeletal muscle to strength training

Objective: To investigate the response to different strength training techniques of growth and myogenic factors in human skeletal muscle, with particular emphasis on satellite cell (SC) activation. Methods: 24 volunteers were divided into two groups and performed a 6-week strength training (group A trained with maximum contraction and group B had training combined with maximum contractions, ballistic movement and stretching–shortening cycles). Muscle biopsies were obtained from triceps brachii 3 days before and 7 days after training. For estimating gene expression of insulin-like growth factor (IGF-1), mechano growth factor (MGF), MyoD and myogenin, real-time RT-PCR was performed. Results: In group A, there was an increase in the 1 repeat maximum (1RM), but no change in Vmax (maximum movement velocity) and an increase in MHC (myosin heavy chain) IIa and a decrease in MHC IIx; in group B both 1RM and Vmax increased significantly along with an increase in MHC IIa and a decrease in MHC I. The MGF gene expression increased significantly in both groups (by 1160% and 59%, respectively), and IGF-1 increased only in group A (by 335%). MyoD and myogenin gene expression increased in group A (by 107% and 94%, respectively) but did not change in group B. Conclusions: Response of growth and myogenic factors occurs during muscular adaptation to a prolonged training, and strength training with different strategies caused different responses with respect to gene expression of these factors. These results suggest that SC activation is involved in the muscular adaptation process to training and might be attributed to MHC isoform transition.

Transcutaneous Oxygen Tension and Doppler Ankle Pressure During Upper and Lower Body Exercise in Patients with Peripheral Arterial Occlusive Disease

The effects of upper and lower body exercise on blood supply to the lower extremi ties were investigated in patients with peripheral arterial occlusive disease (PAOD) by measurements of transcutaneous oxygen tension (tcPO2) and Doppler ankle pressure (DAP). Twenty patients with PAOD (PAOD group) and 10 subjects without PAOD (control group) performed treadmill test (TT), recumbent cycle ergometry (CE), and rowing ergometry (RE) with a fixed seat. The tcPO2 was registered on the calf and DAP was measured at the end of each step of CE and RE. The walking distance in TT of the control group was not limited (> 1000 m), whereas that of the PAOD group was 161 m in median. In the control group there was no significant difference of performance between CE (125 ±33 W) and RE (111 ±24 W), whereas in the PAOD group, performance was lower in CE (72 ±31 W) than in RE (102 ±28 W) (P <0.01). DAP of controls increased during both CE (136 to 165 mmHg) and RE (170 to 213 mmHg), whereas the DAP of the PAOD group decreased during CE (from 85 to 44 mmHg) and remained relatively constant during RE (113 to 101 mmHg). In controls, tcPO2 did not distinctly change during TT (70 to 66 mmHg) and increased during CE (58 to 73 mmHg) and RE (69 to 82 mmHg), whereas in the PAOD group, tcPO2 decreased during TT (66 to 33 mmHg) and CE (50 to 22 mmHg) and remained almost unchanged in RE (64 to 60 mmHg). A hyperbolic relationship was found between tcPO 2 and DAP. In conclusion, during upper body exercise, blood supply to the lower extremities in patients with PAOD was not affected, whereas lower body exercise led to exhaustion of the functional reserve of blood supply. Because of a hyperbolic relationship between tcPO 2 and DAP, tcPO2 remained relatively constant if blood supply was sufficient, but in disturbed blood supply a small change of DAP was accompanied by a great change of tcPO2. Therefore, in critical ischemia the change of tcPO2 was more sensitive than that of DAP.

Clinical Findings and Parameters of Stress and Regeneration in Rowers Before World Championships

The evaluation of the clinical state of an athlete, e.g. of current trainability and of the diagnosis of overload and overtraining, is already one of the most complicated tasks in athletic medicine. Training is not only repetitive physical exercises, but also regular regeneration as an integral part of a successful training program. As already shown in several experimental studies, clinical, metabolic and hormonal findings, including the psychologically-related monitoring of stress and recovery, seem to reflect the clinical state of athletes.Such parameters can be used to monitor training and regeneration in athletes. However, there remains some uncertainty concerning reliability of such parameters for monitoring training and regeneration of elite athletes during periods preparatory to major events like World Championships.This review deals with some of the aspects of these important practical and scientifical questions based on the experience of several preparatory training camps in rowing. Rowing has to be seen as strenuous middle time endurance stress of 5.5 to 8.0 minutes’ duration, for which the athletes perform hughe training programs in which the monitoring of adaptation is essential to prevent long-term overtraining.

Improved training tolerance by supplementation with α-Keto acids in untrained young adults: a randomized, double blind, placebo-controlled trial.

BackgroundExercise causes a variety of physiological and metabolic changes that can in turn reduce exercise tolerance. One of the potential mechanisms responsible for fatigue is “exercise-induced hyperammonemia”. Previous studies have shown that supplementation with amino acids can increase training tolerance. The α-keto acids are biochemical analogs of amino acids and can be converted to amino acids through transamination, thus reducing the cellular ammonia level. This double blind, placebo-controlled study was designed to investigate the effects of α-keto acid supplementation (KAS) on training tolerance, training effect, and stress-recovery state.MethodsThirty-three untrained young male adults underwent four weeks of training (5 sessions/week; 30 minutes running at the individual anaerobic threshold followed by 3 x 3 minute sprints/each session). Throughout the 4 weeks of training and one week of recovery, subjects took α-ketoglutarate (AKG group, 0.2 g/kg/d, n = 9), branched-chain keto acids (BCKA group, 0.2 g/kg/d, n = 12) or isocaloric placebo (control group, n = 12) daily.ResultsThe 4th week training volume, maximum power output and muscle torque were higher in the AKG group (175 ± 42 min, 412 ± 49 Watts and 293 ± 58 Newton meters, respectively, P<0.05) and the BCKA group (158 ± 35, 390 ± 29 and 273 ± 47, P<0.05) than in the control group (92 ± 70, 381 ± 67 and 233 ± 43). The general stress and emotional exhaustion as assessed by the rest-stress-questionnaire-sport after the 3rd week of training increased significantly in the control group (P<0.05), but not in the KAS groups.ConclusionsUnder KAS, subjects could bear a higher training volume and reach a higher power output and peak muscle torque, accompanied by a better stress-recovery-state. Thus, KAS improves exercise tolerance and training effects along with a better stress-recovery state. Whether the improved training tolerance by KAS is associated with effects on ammonia homeostasis requires further observation.

Lung diffusion capacity, oxygen uptake, cardiac output and oxygen transport during exercise before and after an Himalayan expedition

Studies were made of pulmonary diffusion capacity and oxygen transport before and after an expedition to altitudes at and above 4900 m. Maximum power (Pmax) and maximal oxygen uptake (VO2max) were measured in 11 mountaineers in an incremental cycle ergometer test (25W · min−1) before and after return from basecamp (30 days at 4900 m or higher). In a second test, cardiac output (Qc) and lung diffusion capacity of carbon monoxide (DL,CO) were measured by acetylene and CO rebreathing at rest and during exercise at low, medium and submaximal intensities. After acclimatization, VO2max and Pmax decreased by 5.1% [from 61.0 (SD 6.2) to 57.9 (SD 10.2) ml·kg−1, n.s.] and 9.9% [from 5.13 (SD 0.66) to 4.62 (SD 0.42) W·kg−1, n.s.], respectively. The maximal cardiac index and DL,co decreased significantly by 15.6% [14.1 (SD 1.41) 1·min−1 · m−2 to 11.9 (SD 1.44)1·min−1 m−2, P<0.05] and 14.3% [85.9 (SD 4.36)ml·mmHg−1 min−t to 73.6 (SD 15.2) ml · mmHg−1 -min−1, P<0.05], respectively. The expedition to high altitude led to a decrease in maximal Qc, oxygen uptake and DL,CO. A decrease in muscle mass and capillarity may have been responsible for the decrease in maximal Qc which may have resulted in a decrease of DL,CO and an increase in alveolar-arterial oxygen difference. The decrease in DL,CO especially at lower exercise intensities after the expedition may have been due to a ventilation-perfusion mismatch and changes in blood capacitance. At higher exercise intensities diffusion limitation due to reduced pulmonary capillary contact time may also have occurred.

Comparison of whole-Body Thallium Imaging with Transcutaneous PO2 in Studying Regional Blood Supply in Patients with Peripheral Arterial Occlusive Disease

Quantitatively estimating functional reserve of blood supply to the legs in patients with peripheral arterial occlusive disease (PAOD) remains a clinical issue. This study was designed to investigate the regional blood supply to the legs in PAOD patients during exercise by use of thallium 201 (201Tl) whole-body imaging in comparison with transcu taneous PO2 (tcPO2) measurement. Thirty-three patients with PAOD and 10 subjects without PAOD (control) performed an incremental cycle ergometry (CE), while tcPO2 was continuously registered on the involved calf. In the last minute of exercise, 2 mCi of 201Tl was injected intravenously and the 201Tl whole-body images were taken immediately (stress) and four hours (redistrib ution) following stress with a dual-head camera system. Regional blood supply (RBS) (%) was calculated from the geometric mean counts of the region of interest divided by the total counts of the whole body. The performance of PAOD patients was reduced in doing CE, and tcPO2 fell distinctly in PAOD patients (from 51 to 19 mmHg) whereas it increased in controls (from 57 to 67 mmHg). The RBS in PAOD patients was obviously reduced in comparison with that of controls. While in controls the RBS of the calf (3.1%) at stress did not differ from that at redistribution (3.4%), in PAOD patients the redistribution RBS (2.8%) increased as compared with that of stress (1.5%). There was a hyperbolic relationship between stress RBS of the calf and the velocity of tcPO2 fall in PAOD patients during exercise test (velocity of tcPO2 fall = -0.032 + 0.39/RBS, r2 = 0.54, P < 0.05). In conclusion, the RBS determined by 201Tl whole-body imaging is comparable to the tcPO 2 measurement in differentiating patients with PAOD from subjects without PAOD during exercise. Regional 201Tl uptake reflects regional blood supply in PAOD patients. There is a hyperbolic relationship between the RBS derived from 201Tl whole-body imaging and tcPO2 in PAOD patients during exercise, implying that in a critical ischemia the lower the RBS is, the more steeply the tcPO2 decreases.

A test for determining endurance capacity in fencers.

Until now endurance in fencers has been tested by non-specific ergometer tests even though the movement patterns during fencing are considerably different. The aim of the study was to evaluate a newly developed fencing-specific endurance test (FET). 2 studies were carried out: 28 fencers were tested by FET with fencing-specific footwork and incremental tests on cycle (CE) and treadmill ergometer (TM) in a random order. Afterwards fencing bouts (BOU) were conducted to determine specific physical load. Blood lactate and heart rates were measured. In a second study another group of 18 international and 20 national level fencers conducted FET to explore differences between groups. Comparison of CE, TM, FET and BOU revealed a significant correlation between FET and BOU (r=0.80, p<0.01), heart rates during CE and TM were significantly lower than in bouts (p<0.01). Performance at CE and TM hardly correlated with FET (r=0.30, p<0.05; r=0.31, p<0.05). Elite-fencers showed significantly better performance than non-elite fencers in FET (p<0.01). FET was suitable for determining specific endurance in fencers, allows a better assessment of physical demands during bouts than conventional ergometry and can be used to distinguish between fencers of different levels.