High cycling cadence reduces carbohydrate oxidation at given low intensity metabolic rate.

Cycling cadence (RPM)-related differences in blood lactate concentration (BLC) increase with increasing exercise intensity, whilst corresponding divergences in oxygen uptake ([Formula: see text]O2) and carbon dioxide production ([Formula: see text]CO2) decrease. Aim of the present study was to test whether a higher RPM reduces the fraction (%) of the [Formula: see text]O2 used for carbohydrate oxidation (relCHO) at a given BLC. Eight males (23.9 ± 1.6 yrs; 177 ± 3 cm; 70.3 ± 3.4 kg) performed incremental load tests at 50 and 100 RPM. BLC, [Formula: see text]O2 and [Formula: see text]CO2 were measured. At respiratory exchange ratios (RER) < 1, relCHO were calculated and the constant determining 50 % relCHO (kCHO) was approximated as a function of the BLC. At submaximal workload [Formula: see text]O2, [Formula: see text]CO2, and relCHO were lower (all p < 0.002; η(2) > 0.209) at 50 than at 100 RPM. No differences were observed in [Formula: see text]O2peak (3.96 ± 0.22 vs. 4.00 ± 0.25 l · min (-1)) and RERpeak (1.18 ± 0.02 vs. 1.15 ± 0.02). BLC was lower (p < 0.001; η(2) = 0.680) at 50 than at 100 RPM irrespective of cycling intensity. At 50 RPM, kCHO (4.2 ± 1.4 (mmol · l (-1))(3)) was lower (p = 0.043; η(2) = 0.466) than at 100 RPM (5.9 ± 1.9 (mmol · l (-1))(3)). This difference in kCHO reflects a reduced CHO oxidation at a given BLC at 100 than at 50 RPM. At a low exercise intensity, a higher cycling cadence can substantially reduce the reliance on CHO at a given metabolic rate and/or BLC.

Pilot investigation of the oxygen demands and metabolic cost of incremental shuttle walking and treadmill walking in patients with cardiovascular disease.

OBJECTIVE: To determine if the metabolic cost of the incremental shuttle-walking test protocol is the same as treadmill walking or predicted values of walking-speed equations. SETTING: Primary care (community-based cardiac rehabilitation). PARTICIPANTS: Eight Caucasian cardiac rehabilitation patients (7 males) with a mean age of 67±5.2 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Oxygen consumption, metabolic power and energy cost of walking during treadmill and shuttle walking performed in a balanced order with 1 week between trials. RESULTS: Average overall energy cost per metre was higher during treadmill walking (3.22±0.55 J kg/m) than during shuttle walking (3.00±0.41 J kg/m). There were significant post hoc effects at 0.67 m/s (p<0.004) and 0.84 m/s (p<0.001), where the energy cost of treadmill walking was significantly higher than that of shuttle walking. This pattern was reversed at walking speeds 1.52 m/s (p<0.042) and 1.69 m/s (p<0.007) where shuttle walking had a greater energy cost per metre than treadmill walking. At all walking speeds, the energy cost of shuttle walking was higher than that predicted using the American College of Sports Medicine walking equations. CONCLUSIONS: The energetic demands of shuttle walking were fundamentally different from those of treadmill walking and should not be directly compared. We warn against estimating the metabolic cost of the incremental shuttle-walking test using the current walking-speed equations.

[Cost evaluation of a model for integrated care of seriously mentally ill patients]. / Kostenevaluation eines Modells der Integrierten Versorgung für schwer psychisch Kranke.

BACKGROUND: The model for integrated care (IC) of those seriously mentally ill patients insured with the DAK-Gesundheit health insurance and various Betriebskrankenkassen (members of the VAG Mitte) from the regions Berlin, Brandenburg, Lower Saxony and Bremen allows a complex treatment in the outpatient setting which consists of psychiatrists, general practitioners and clinicians, psychiatric nursing, sociotherapy (only in Berlin), internal medicine quality circles, orientation on treatment guidelines and conceptual consensus with the relevant care clinics. The aim of the evaluation is to illustrate the health economic effects of IC. METHODS: In the period from 2006 to 2010 insured members of the DAK-Gesundheit and other involved health insurance companies with a serious mental illness, a significant impairment of social functioning and the need to be treated to avoid or substitute an in-hospital stay were included in the integrated care. The cost perspective was that of the statutory health insurance companies. For the health economic evaluation, the utilisation of continuous IC over 18 months was compared to the last 18 months prior to the inclusion in IC. The clinical findings were gathered quarterly during the IC using CGI (Clinical Global Impressions) and GAF (Global Assessment of Functioning Scale). RESULTS: A total of 1 364 patients receiving IC in 66 doctor's practices were documented (of those, 286 had diagnoses of ICD-10 F2, 724 ICD-10 F32-F39). The median age was 48.8 years, 69% were female. 24% had their own source of income, 40% were on the pension, and the rest of the patients were receiving transfer benefits in some form. In 54% of the cases IC was used to avoid an in-hospital stay, in 46% of the cases to substitute an in-hospital stay. The degree of the CGI was 5.5 on average at the time of inclusion and the GAF score was 36.5 on average. The 226 patients with continuous documentation over 18 months were included in the health economic analysis. The number of days spent in hospital was lower during the IC period as compared to the 18 months prior to IV (11.8 vs. 28.6 days, p<0.001), the inpatient costs were lower (5 929 ± 13 837 Euro vs. 2 458 ± 6 940 Euro, p<0.001), the total was not significantly changed (7 777 ± 14 263 Euro vs. 7 321 ± 7 910 Euro, p=0.65). The substantial reduction of inpatient costs was compensated by the additional costs for medication and the costs of the complex outpatient care. Results were comparable for the 2 subgroups of schizophrenic/schizoaffective (n=66, 40.9 vs. 17.9 days, p=0.03; inpatient cost 9 009 ± 15 677 Euro vs. 3 650 ± 8 486 Euro, p=0.02; total expenditures 11 789 ± 15 975 Euro vs. 9 623 ± 9 262 Euro, p=0.33) and unipolar depressive patients (n=90, 29.8 vs. 9.8 days, p=0.006; inpatient cost 5 664 ± 14 921 Euro vs. 1 967 ± 5 276 Euro, p=0.02; total expenditures 7 146 ± 15 164 Euro vs. 6 234 ± 6 292 Euro, p=0.57). CONCLUSION: The IC was able to considerably reduce the utilisation of inpatient treatment through offering a complex range of services in the outpatient setting and allowed for a weight-shift in a low-threshold comprehensive care structure without an increase in costs from the statutory health insurance companies' perspective. For a detailed description of clinical effects further studies are required.

Variability of blood lactate during and between given constant prolonged cycling power.

AIM: Blood lactate concentration (BLC) has been the basis of rational performance diagnostics for almost five decades. Aim of this study was to identify the variability of the BLC during repeated constant power tests (VC-BLC) and to quantify the corresponding variability of changes in the BLC over time (VC-BLC-Difference). METHODS: Twelve healthy male subjects (24.8±3-8 years, 182.9±7.5 cm, 75.7±7.1 kg, ·VO2peak: 4.1±0.6 l min-1) performed four series of three constant power tests at exercise intensities of 45% (A), 60% (B), 75% (C) and 90% (D) of VO2peak. Blood sampling was conducted before, at the end of every 5th min and at the end of each test terminated ahead of schedule. RESULTS: BLC was different at all exercise intensities from minute five onwards. Power output was equivalent to 142.1±18.9 W (A), 196.3±25.2 W (B), 247.9±30.3 W (C) and 302.5±38.4 W (D). VC-BLC varied between 9±2.2% and 21±10.1%. VC-BLC and VC-BLC-Difference between 10th and 30th min correlated inversely with mean BLC level and BLC-Difference respectively. CONCLUSION: By providing first data on constant power test VC-BLC and VC-BLC-Difference this study might help to improve performance diagnostics and training control in sports medicine and medical exercise therapy by assisting in selecting and monitoring exercise intensity. Performance monitoring with BLC-Differences is feasible at moderate and high exercise intensities; single BLC measurements at termination of tests might not be sufficient.

Spring mass characteristics of the fastest men on Earth.

The spring mass model has widely been used to characterize the whole body during running and sprinting. However the spring mass characteristics of the world's fastest men are still unknown. Thus the aim of this study was to model these characteristics for currently the 3 fastest men on earth (Usain Bolt, Tyson Gay and Asafa Powell). This was done by using data collected during the 2009 World championships in Berlin and the modelling method of Morin et al. 21. Even though Bolt achieved the greatest velocity (12.3 m.s - 1) over the 60-80 m split compared to his competitors, his estimated vertical stiffness (355.8 kN.m - 1) and leg stiffness (21.0 kN.m - 1) were significantly lower than his competitors. This reduction in stiffness is a consequence of Bolt's longer contact time (0.091 s) [corrected] and lower step frequency (4.49 Hz).Thus Bolt is able to run at a greater velocity but with lower stiffness compared to his competitors.

Sports behaviour among HIV-infected versus non-infected individuals in a Berlin cohort.

Physical activity has been recommended based on beneficial effects described in HIV-infected patients. However, such guidelines do not take into account actual sport behaviours and general attitudes towards physical activity. To evaluate actual sport activity and attitudes towards sport in HIV-infected versus non-infected individuals we conducted an anonymous questionnaire investigating the prevalence, as well as possible changes, in sports engagement and the overall attitude to physical activity. A total of 283 patients of a general care facility specialized in the treatment of HIV/AIDS in Berlin, Germany, participated; 124 were HIV infected and 159 were non-infected, mostly men who have sex with men (MSM) (88%), with a median age of 35 years. The HIV-infected participants had a median CD4+ count of 554 cells/µL and 48.8% of them were using antiretroviral therapy (ART) at the time of survey. The proportion of patients actually performing physical activity was significantly lower (P = 0.028) within the HIV-infected group (61.3%) than within the non-infected group (74.2%). This difference remained significant after accounting for possible confounders such as age, gender, injecting drug use and sexual preferences. Previously reported sport activity prevalence was similar in both groups on leaving school. From our data we could not identify an association between the time of HIV diagnosis and changes in sports activity. In conclusion, fewer HIV-infected individuals report physical activity than non-infected individuals. Sociodemographic studies to evaluate potential differences in sports behaviour are required in order to inform exercise guidelines for HIV-infected patients.

Teleoanticipation in all-out short-duration cycling.

OBJECTIVE: to investigate the effect of all-out cycling test duration on indices of power, anaerobic lactic energy metabolism, perceived exertion and mood. METHODS: nine physically active men undertook four all-out cycling tests of 5, 15, 30 or 45 s from seated stationary start on an ergometer fit with power cranks. The participants completed a Profile of Mood States questionnaire before each test and indicated perceived exertion immediately post-test (Borg 6-20 scale). Indices of anaerobic lactic metabolism were determined from blood lactate concentrations. RESULTS: pacing strategy was apparent in the 45-s tests with lower peak (p<0.01) and mean power in the initial 10 s compared to the 5- and 15-s tests (p<0.05). The first 15 s of the 30- and 45-s tests revealed lower fatigue indices compared to the 15-s tests (p<0.05) indicating some pacing in the 30-s tests. Perceived exertion increased with duration, with no difference between the 15- and 30-s tests (p>0.05). Extravascal lactate generation (reflecting exercising muscle lactate production) explained 59% of the variance in perceived exertion. There was no effect of knowledge of test duration on mood states or total mood disturbance (p>0.05). CONCLUSIONS: an all-out pacing strategy was apparent for at least up to 15 s, with indicators of dampened power in both 30 and 45 s sprints. Reduced power at the start of all-out long-duration sprints support a central control of at least initial pacing strategy.

Metabolic and performance effects of warm-up intensity on sprint cycling.

Warm-up is generally considered beneficial for performance, although the reduction in anaerobic glycolytic metabolism may be detrimental to sprinting. This study examined the effect of warm-up intensity on metabolism and performance in sprint cycling. The mean power was determined during a 1-min sprint on 11 trained males preceded by easy (WE), moderate (WM) or hard (WH) warm-up and a 10-min recovery. Aerobic, anaerobic glycolytic and phosphocreatine energy provision to the sprint was determined from oxygen uptake and lactate production. Blood lactate concentration before the sprint increased with the warm-up intensity (WE: 1.2±0.3; WM: 2.0±0.3; WH: 4.2±0.9 mmol/L, P<0.001), with WH reducing the increase in lactate production during exercise vs WE (WE: 11.6±1.6; WM: 10.9±1.9; WH: 9.2±1.4 mmol/L, P<0.05). Despite the lower relative anaerobic glycolytic energy provision in WH vs WE (WH: 38±5; WM: 36±6; WE: 34±3%, P<0.05), the mean power was unaffected (WE: 516±28; WM: 521±26; WH: 526±34 W, P>0.05) due to increased oxygen uptake in WH during the sprint (WE: 3.2±0.4; WM: 3.3±0.3; WH: 3.4±0.4 liters, P<0.05). This study supports a warm-up-induced reduction in glycolytic rate, although sprint performance, at least of a long duration, may be maintained due to increased oxygen utilization.

Cardiospecificity of the 3rd generation cardiac troponin T assay during and after a 216 km ultra-endurance marathon run in Death Valley.

BACKGROUND: The reasons for the appearance of cardiacspecific troponin (cTnT) after strenuous exercise are unclear. The aim of the present study was to evaluate the cardiospecificity of the 3(rd) generation cardiac cTnT assay during and after an ultra-endurance race of 216 km at extreme environmental conditions in Death Valley. STUDY DESIGN AND METHODS: We measured serially cTnT, creatine kinase (CK), activity and mass of the isoenzyme MB of CK (CK-MB(act) and CK-MB(mass)), and myoglobin in 10 well-trained athletes before, repeatedly during and after the race. RESULTS: Six of 10 participants finished the race within a preset time of 60 hours. Postrace values of biochemical markers CK, CK-MB(act), CKMB(mass), and myoglobin were significantly increased compared to baseline (p<0.05). CK-MB(act) increased from (median (25(th)/ 75(th)percentile) 12 (10/13) U/L to 72 (32/110) U/L, CK-MB(mass) from 3.9 (2.9/5.6) U/L to 65 (18/80) U/L and CK increased from median 136 (98/ 228) U/L to 3,570 (985/6,884) U/L respectively. Pre-race myoglobin was 27 (22/31) microg/l compared to 530 (178/657) microg/l after the run. One runner developed significant exercise-induced rhabdomyolysis with spontaneous recovery. cTnT values remained below the 99(th) percentile reference limit in all athletes including the runner who developed significant rhabdomyolysis (peak CK 27,951 U/L). CONCLUSIONS: Strenuous endurance exercise, even under extreme environmental conditions, does not result in structural myocardial damage in well-trained ultra-endurance athletes. We found no crossreactivity between cTnT and CK, neither in exercise-induced skeletal muscle trauma nor after rhabdomyolysis underscoring the excellent analytical performance of 3(rd) generation cTnT assay.

Mechanically versus electro-magnetically braked cycle ergometer: performance and energy cost of the Wingate Anaerobic Test.

Performance and metabolic profiles of the Wingate Anaerobic Test (WAnT) were compared between a mechanically resisted (ME) and an electro-magnetically braked (EE) cycle ergometer. Fifteen healthy subjects (24.0+/-3.5 years, 180.5+/-6.1 cm, 75.4+/-11.9 kg) performed a WAnT on ME, and EE 3 days apart. Performance was measured as peak power (PP), minimum power (MP), mean power (AP), time to PP (TTPP), fatigue rate (FR), and maximum cadence (RPM(MAX)). Lactic (W (LAC)) and alactic (W (PCR)) anaerobic energy were calculated from net lactate appearance and the fast component of post-exercise oxygen uptake. Aerobic metabolism (W (AER)) was calculated from oxygen uptake during the WAnT. Total energy cost (W (TOT)) was calculated as the sum of W (LAC), W (PCR), and W (AER). There was no difference between ME and EE in PP (873+/-159 vs. 931+/-193 W) or AP (633+/-89 vs. 630+/-89 W). In the EE condition TTPP (2.3+/-0.7 vs. 4.3+/-0.7 s) was longer (P<0.001), MP (464+/-78 vs. 388+/-57 W) was lower (P<0.001), FR (15.2+/-5.2 vs. 20.5+/-6.8%) was higher (P<0.005), and RPM(MAX) (168+/-18 vs. 128+/-15 rpm) was slower (P<0.001). There was no difference in W (TOT) (1,331+/-182 vs. 1,373+/-120 J kg(-1)), W (AER) (292+/-76 vs. 309+/-72 J kg(-1)), W (PCR) (495+/-153 vs. 515+/-111 J kg(-1)) or W (LAC) (545+/-132 vs. 549+/-141 J kg(-1)) between ME and EE devices. The EE produces distinctly different performance measures but valid metabolic WAnT results that may be used to evaluate anaerobic fitness.

Experiment and computer-aided simulation: complementary tools to understand exercise metabolism.

During the last two decades the concept of the MLSS (maximal lactate steady state) has been established. The MLSS detects the highest level of the BLC (blood lactate concentration) and the corresponding workload (MLSS workload) that can be maintained over time without continual BLC accumulation. In spite of a lack of experimental and/or theoretical foundation, it has been speculated that the level of the MLSS may decrease with increasing performance capacity. The potential inter-relationship between performance capacity and BLC response to prolonged constant workload will be analysed based on a recent study, which provided evidence that the MLSS is independent of performance whereas MLSS workload increases with performance capacity, and by a computer-aided simulation. The simulated model modifies and combines previous theories put forward to explain the response of BLC to exercise and incorporates a theory about limiting factors of oxygen transport to the muscle cell. Simulations consider the BLC response to selected prolonged constant workloads while paying special respect to changes in body structure and substrate utilization, which are generally accepted as limiting factors of performance capacity. This complex modulation of appearance and disappearance of lactate during constant prolonged exercise seems to support the experimental results, which indicated independence between MLSS and performance capacity.

Markers of coagulation, fibrinolysis and angiogenesis after strenuous short-term exercise (Wingate-test) in male subjects of varying fitness levels.

It was the aim of the study to analyse the haemostatic system during a high standardized intensive short-term (30 s) exercise (anaerobic Wingate test). Blood samples were taken from 15 male subjects before (t0 ), and within 2 (t1 ), 9 (t2 ) and 30 min (t3 ) after the test. We found that the partial thromboplastin time was markedly shortened, whereas the prothrombin time increased slightly from t0 to t1 (p < 0.002) and remained elevated (t3, p < 0.046). Factor VIII increased from t0 to t1 (p < 0.001) and remained elevated as well (t3, p < 0.001). Fibrin monomers were approximately 15 times higher immediately post-exercise (t1, p < 0.001) and continued to be elevated (t3, p < 0.004). The tissue plasminogen activator increased by 4 times after exercise (t1, p < 0.001) and remained elevated (t3, p < 0.002). The d-dimers increased from t0 to t1 (p < 0.001) as well and remained elevated (t3, p < 0.005). Thrombopoietin concentrations were unchanged, whereas the vascular endothelial growth factor increased immediately post-exercise (t0 to t1, p < 0.011 resp. at t2 p < 0.019) and returned to the control level at t3 (p < 0.878). In conclusion, it was found that prothrombotic markers and, even more pronounced, those of the fibrinolytic system were increased. The study provides evidence that due to intensive short-term exercise the balance of the haemostatic system is shifted to a higher equilibrium. Theoretically, the data show that in the case of a subject with risk factors such as impaired fibrinolysis, unfavourable conditions cannot be excluded.

How anaerobic is the Wingate Anaerobic Test for humans?

The Wingate Anaerobic Test (WAnT) is generally used to evaluate anaerobic cycling performance, but knowledge of the metabolic profile of WAnT is limited. Therefore the energetics of WAnT was analysed with respect to working efficiency and performance. A group of 11 male subjects [mean (SD), age 21.6 (3.8) years, height 178.6 (6.6) cm, body mass 82.2 (12.1) kg] performed a maximal incremental exercise test and a WAnT. Lactic and alactic anaerobic energy outputs were calculated from net lactate production and the fast component of the kinetics of post-exercise oxygen uptake. Aerobic metabolism was determined from oxygen uptake during exercise. The WAnT mean power of 683 (96.0) W resulted from a total energy output above the value at rest of 128.1 (23.2) kJ x 30 s(-1) [mean metabolic power=4.3 (0.8) kW] corresponding to a working efficiency of 16.2 (1.6)%. The WAnT working efficiency was lower (P < 0.01) than the corresponding value of 24.1 (1.7)% at 362 (41) W at the end of an incremental exercise test. During WAnT the fractions of the energy from aerobic, anaerobic alactic and lactic acid metabolism were 18.6 (2.5)%, 31.1 (4.6)%, and 50.3 (5.1)%, respectively. Energy from metabolism of anaerobic lactic acid explained 83% and 81% of the variance of WAnT peak and mean power, respectively. The results indicate firstly that WAnT requires the use of more anaerobically derived energy than previously estimated, secondly that anaerobic metabolism is dominated by glycolysis, thirdly that WAnT mechanical efficiency is lower than that found in aerobic exercise tests, and fourthly that the latter finding partly explains discrepancies between previously published and the present data about the metabolic profile of WAnT.

Exercise-induced changes in blood levels of alpha-tocopherol.

Levels of alpha-tocopherol (alphaT) in plasma and red blood cells (RBC) are assumed to be modulated by exercise. The mechanisms involved remain to be established. We examined the influence of different running bouts on the content of alphaT in RBC (alphaT(RBC)), the concentration in plasma (alphaTplasma), and their relationship with lipolysis, as indicated by changes (delta) in plasma glycerol concentration ([glycerol]). Eleven healthy runners [mean (SD) age 35 (9) years, height 177.3 (7.6) cm, body mass 69.6 (9.4) kg, and peak oxygen consumption, VO2peak, 57.8 (4.8) ml.kg(-1).min(-1)] performed an incremental treadmill test [duration 17 (2) min, peak velocity, vpeak 4.8 (0.4) m.s(-1)], a training run [173 (12) min, 57 (4)% vpeak] and a marathon [197 (24) min, 75 (5)% vpeak]. Before (pre) and after (post) each run, haematological and lipid parameters, alphaT(RBC) and alphaTplasma were determined. Haemoconcentration was observed after each run. delta[glycerol] was +0.10 (0.10) mmol.l(-1), +0.40 (0.14) mmol.l(-1) and +0.51 (0.15) mmol.l(-1) in the treadmill test, training run and marathon, respectively. When corrected for haemoconcentration, values of alphaTplasma decreased [-5.4 (7.5)%, P< 0.05] in the treadmill test, were unchanged [+0.7 (8.7)%] in the training run and increased [+7.8 (8.3)%, P<0.05] in the marathon. alphaT(RBC) decreased [pre vs post: 22.7 (3.2) nmol.g haemoglobin(-1) (nmol.g Hb(-1)) vs 18.9 (3.8) nmolg Hb(-1), P < 0.05] in the treadmill test and was not significantly changed in either the training run [20.8 (1.9) nmol.g Hb(-1) vs 19.1 (3.0) nmol.g Hb(-1)] or the marathon [21.6 (2.9) nmol.g Hb(-1) vs 23.4 (2.7) nmol.g Hb(-1)]. deltaalphaT(RBC) and deltaalphaTplasma were positively related to delta[glycerol]. The reduction in alphaTRBC and alphaTplasma after short-lasting heavy exercise indicates the consumption of alphaT, whereas the association between deltaalphaT and delta[glycerol] suggests mobilisation of alphaT, especially in long-lasting exercises. However, although alphaT appears to be influenced by exercise, the results suggest a well-balanced regulation of alphaT during exercise resulting in small, and only in part, significant deltaalphaT in blood.

Dependence of the maximal lactate steady state on the motor pattern of exercise.

BACKGROUND: Blood lactate concentration (BLC) can be used to monitor relative exercise intensity. The highest BLC representing an equilibrium between lactate production and elimination is termed maximal lactate steady state (MLSS). MLSS is used to discriminate qualitatively between continuous exercise, which is limited by stored energy, from other types of exercise terminated because of disturbance of cellular homoeostasis. AIM: To investigate the hypothesis that MLSS intraindividually depends on the mode of exercise. METHODS: Six junior male rowers (16.5 (1.4) years, 181.7 (3.1) cm, 69.8 (3.3) kg) performed incremental and constant load tests on rowing and cycle ergometers. Measurements included BLC, sampled from the hyperaemic ear flap, heart rate, and oxygen uptake. MLSS was defined as the highest BLC that increased by no more than 1.0 mmol/l during the final 20 minutes of constant workload. RESULTS: In all subjects, MLSS was lower (p < or = 0.05) during rowing (2.7 (0.6) mmol/l) than during cycling (4.5 (1.0) mmol/l). No differences between rowing and cycling were found with respect to MLSS heart rate (169.2 (9.3) v 172.3 (6.7) beats/min), MLSS workload (178.7 (29.8) v 205.0 (20.7) W), MLSS intensity expressed as a percentage (63.3 (6.6)% v 68.6 (3.8)%) of peak workload (280.8 (15.9) v 299.2 (28.4) W) or percentage (76.4 (3.4)% v 75.1 (3.0)%) of peak oxygen uptake (60.4 (3.4) v 57.2 (8.6) ml/kg/min). CONCLUSIONS: In rowing and cycling, the MLSS but not MLSS workload and MLSS intensity intraindividually depends on the motor pattern of exercise. MLSS seems to decrease with increasing mass of the primarily engaged muscle. This indicates that task specific levels of MLSS occur at distinct levels of power output per unit of primarily engaged muscle mass.

Measured fraction of carboxyhaemoglobin depends on oxygen saturation of haemoglobin.

The use of the OSM3 oximeter for measurement of the fraction of carboxyhaemoglobin (FCOHb) in blood allows for estimation of total circulating haemoglobin mass (Hb(tot)) by using the carbon monoxide rebreathing method. To ensure high accuracy of Hb(tot) estimation, potential sources of analytical errors should be identified and adjusted for. Based on observed differences in results of measured FCOHb between simultaneously sampled, arterialized and venous blood samples we investigated the influence of haemoglobin oxygen saturation (sO2) on results of measured FCOHb. Blood from nine healthy non-smokers was tonometered with gas mixtures containing 94% N2 or air and 6% CO2. The resulting oxygenated and deoxygenated specimens were mixed in different proportions to obtain varying sO2 values in the same blood. sO2, fractions of dyshaemoglobins, pO2, pCO2 and pH were measured at each step. FCOHb was significantly (p<0.001) higher in oxygenated (median, range: 0.6%, 0.4-0.9%) compared to deoxygenated (-0.2%, -0.5-0.0%) blood. Regression analysis identified the sO2 as the most important factor explaining 86% of the variance in observed changes in FCOHb. The observed sO2 effect has important implications on calibration procedure of OSM3, accuracy of measured FCOHb, and FCOHb dependent calculations such as estimation of Hb(tot) and related quantities. If the highest accuracy of FCOHb measurement is needed, an sO2 effect on results of measured FCOHb has to be considered and adjusted for.

Inhibition of poly(ADP-ribose) polymerase activity accelerates T-cell lymphomagenesis in p53 deficient mice.

Cells that lack PARP-1 activity are limited in their ability to repair DNA single strand breaks and respond to DNA damage with a strong accumulation of p53 and enhanced rates of apoptotic cell death. We have generated combinatorial mutant mice that both lack p53 and PARP-1 activity due to the expression of a dominant negative PARP-1 allele targeted to T-cells by the lck promoter. Here we report that these double mutant mice develop T-cell lymphoma at a significantly reduced latency period compared to single p53 null mice that are already cancer prone. We demonstrate that the absence of p53 does not only protect T-cells from lck-PARP-DBD transgenic mice from apoptosis but also abrogates the DNA damage induced cell cycle arrest in the G1 phase. T-cells from double mutant mice continue to proliferate after the induction of DNA strand breaks, are limited in their DNA repair capacity and cannot be eliminated by apoptosis. These results indicate that PARP-1 and p53 cooperate in the suppression of tumorigenesis by maintaining genomic integrity after DNA damage through the activation of a G1/S cell cycle checkpoint the initiation of DNA repair and the induction of cell death.

DNA excision repair and DNA damage-induced apoptosis are linked to Poly(ADP-ribosyl)ation but have different requirements for p53.

Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. The enzymatic activity of PARP is induced upon DNA damage and the PARP protein is cleaved during apoptosis, which suggested a role of PARP in DNA repair and DNA damage-induced cell death. We have generated transgenic mice that lack PARP activity in thymocytes owing to the targeted expression of a dominant negative form of PARP. In the presence of single-strand DNA breaks, the absence of PARP activity correlated with a strongly increased rate of apoptosis compared to cells with intact PARP activity. We found that blockage of PARP activity leads to a drastic increase of p53 expression and activity after DNA damage and correlates with an accelerated onset of Bax expression. DNA repair is almost completely blocked in PARP-deficient thymocytes regardless of p53 status. We found the same increased susceptibility to apoptosis in PARP null mice, a similar inhibition of DNA repair kinetics, and the same upregulation of p53 in response to DNA damage. Thus, based on two different experimental in vivo models, we identify a direct, p53-independent, functional connection between poly(ADP-ribosyl)ation and the DNA excision repair machinery. Furthermore, we propose a p53-dependent link between PARP activity and DNA damage-induced cell death.