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PubMed2004

Norandrosterone and noretiocholanolone concentration before and after submaximal standardized exercise.

19-Norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) are the two main urinary indicators used to detect illegal use of nandrolone. Recent studies showed that 19-NA and 19-NE can be endogenously produced in non-treated humans. The concentrations were close to the threshold of the International Olympic Committee (IOC), i.e. 2 ng/ml for men and seem to increase after prolonged intense effort. Androgens are involved in the biosynthesis of estrogens and estrogen has a protective effect against skeletal muscle damage following eccentric exercise. Furthermore, the testicular tissue can synthesize 19-norandrogens from androgens, we hypothetisize that the 19-norandrogen production might be influenced by muscle damage following eccentric exercise. Therefore the purpose of this study is to examine if three different exercise methods will influence the urinary concentration of 19-NA and 19-NE in healthy young subjects. Fifteen amateur hockey players undertook a 30 min submaximal standardized exercise protocol. They were randomised for three different types of exercise, namely a cycle ergometer test (cyclic muscle activity), a treadmill test (concentric muscle activity), or a bench-steptest (eccentric muscle activity) at a target heart rate corresponding to 65 % (+/- 5 %) of Karvonen heart rate. Urine samples were obtained before the test and 60 min and 120 min after the end of exercise. Subjects completed a Likert scale of muscle soreness before and 12 h after exercise. 19-NA and 19-NE were determined by gas chromatography-tandem mass spectrometry (GC-MS-MS). Baseline urinary 19-NA and 19-NE concentrations were under limit of detection of 0.05 ng/ml, except for one sample (0.13 ng/ml). No 19-NA or 19-NE could be detected post exercise. In our experimental conditions, the exercise mode (eccentric or concentric) had no impact on 19-NA or 19-NE excretion. Our findings confirm that the current International Olympic Committee threshold level for nandrolone metabolites is sufficiently high to avoid false positive cases.

Adult↗
PubMed1998

Mitochondrial permeability transition is altered in early stages of carcinogenesis of 2-acetylaminofluorene.

The tumour promoting properties of carcinogenic 2-acetylaminofluorene (AAF) in rat liver are essentially unknown. We proposed that mitochondria are a target for the cytotoxic effects of 2-nitrosofluorene (NOF), a metabolite of AAF, since NOF induces a redox-cycle at complex I and complex III of the respiratory chain, and impairs respiration and oxidative phosphorylation. We now demonstrate that NOF is a potent inducer of the mitochondrial permeability transition pore (PTP) in isolated mitochondria. In the presence of Ca2+, NOF induced rapid swelling of mitochondria in a dose-dependent manner and depolarized the mitochondrial membrane. Permeability transition as well as depolarization were abolished completely by pre-incubation with the PTP inhibitor cyclosporin A. To study whether the PTP is involved in in vivo toxicity, rats were fed a diet containing AAF (0.04%) for 2 weeks. After isolation of mitochondria, permeability transition was induced by high Ca2+ concentrations (150-400 microM) or phosphate plus Ca2+. Swelling was determined as maximal rate of absorption decrease at 540 nm (delta A/delta t). Surprisingly, delta A/delta t-values of mitochondria from AAF-fed rats were significantly lower (16.3 +/- 4.8 x 10(3)/min) than of mitochondria from control animals (32.7 +/- 4.1 x 10(3)/min; P < 0.02). In the presence of phosphate (15 mM), delta A/delta t-values of mitochondria from AAF-fed rats were even lower (10% of control). Moreover, the membrane potential which was dissipated rapidly by the PTP-inducer NOF (30 microM) at a Ca2+ concentration of 80 microM in mitochondria from control animals, remained constant in mitochondria of AAF-treated rats. We therefore propose that the regulation of the PTP is altered on chronic AAF-feeding. The increased resistance of mitochondria against permeability transition may alter the threshold for apoptosis and thus suppress apoptosis. We also discuss the role of epigenetic modifications in early stages of carcinogenesis.

2-Acetylaminofluorene↗
PubMed2000

[The effect of cardiovascular rehabilitation on the variability of the RR cycle after a first uncomplicated acute myocardial infarct].

BACKGROUND: The aim of this study was to verify the changes in the autonomic balance by means of heart rate variability assessment in patients with myocardial infarction referred for cardiac rehabilitation. METHODS: We studied 122 patients (79 males, 43 females, mean age 56 +/- 5 years), with a first uncomplicated myocardial infarction (anterior 48, thrombolysis 72), Killip class 1, preserved left ventricular function (ejection fraction 49 +/- 6%). All patients were free of inducible residual ischemia. Four weeks after myocardial infarction, patients were randomized into two groups; Group 1 (n = 58) referred for an 8 week cardiac rehabilitation program (scheduled: 24 sessions); Group 2 (n = 64): normal daily physical activity. During a 24-hour Holter ECG monitoring the following parameters were calculated in pharmacological wash-out at randomization (T0) and at the end of cardiac rehabilitation/control period (T1): mean value of RR intervals (RR), its standard deviation (SDNN), pNN50, rMSSD in the time domain; low frequency (LF) and high frequency (HF) value and the LF/HF ratio in the frequency domain. T1-T0 changes in percent values (delta %) were considered and compared between the two groups. RESULTS: Thirty-one patients were excluded from the study either for insufficient adhesion to the cardiac rehabilitation program (< 13 sessions, 22 patients) or recurrent ischemia (3 Group 1 patients and 3 Group 2 patients) and non-assessable 24-hour Holter ECG monitoring (3 patients). Thirty-one Group 1 patients and 60 Group 2 patients completed the study with a first and a second 24-hour Holter ECG monitoring performed at 30 +/- 3 days and 60 +/- 4 days respectively. At the same time an ergospirometric test was performed to evaluate cardiopulmonary function by means of exercise time, maximum oxygen consumption, anaerobic threshold, exercise time at the anaerobic threshold, and maximum oxygen consumption at the anaerobic threshold. Twenty-eight Group 1 patients and 44 Group 2 patients completed the study with a first and a second ergospirometric test. Baseline heart rate variability parameters were comparable in the two groups. During the observation period only in Group 1 patients heart rate variability parameters changed significantly: RR (Group 1 = +18.3 +/- 21.3; Group 2 = +4.2 +/- 5.2, p = 0.000), pNN50 (Group 1 = 45.0 +/- 38.9; Group 2 = +24.2 +/- 34.7, p = 0.011), HF (Group 1 = +81.6 +/- 124; Group 2 = -28.7 +/- 75.4, p = 0.014) and LF/HF ratio (Group 1 = -26.0 +/- 16.1; Group 2 = -4.9 +/- 6.1, p = 0.062). There were no significant differences in SDNN, rMSSD and LF. A linear correlation between delta LF/HF ratio and baseline LF/HF ratio values was found in Group 1 (r = 0.489, p = 0.006), whereas no correlation was found between this parameter and age, ejection fraction, creatine phosphokinase, and infarct localization. Group 1 patients had a significant improvement in exercise tolerance compared to Group 2 patients. CONCLUSIONS: A cardiac rehabilitation program positively modifies the sympatho-vagal balance in patients with uncomplicated myocardial infarction, increasing the parasympathetic tone and exercise tolerance.

Aged↗
PubMed1998

Gonadotrophin profiles and dioestrous pulsatile release patterns in mares as determined by collection of jugular blood at 4 h intervals throughout an oestrous cycle.

In mares, dioestrous FSH profiles based on once-a-day sampling are variable; however, the pulsatility of plasma FSH, which has been suggested by limited windows of intensive sampling, may contribute to this variability. Jugular blood from six mares was sampled at 4 h intervals throughout an ovulatory cycle to determine cyclic FSH and LH patterns more accurately and to measure gonadotrophin pulse frequency during dioestrus. Synchronous pulses of FSH and LH occurred regularly in all mares between day 4 and day 12 (ovulation = day 0) with a mean (+/- SEM) frequency of 1.9 +/- 0.1 (FSH) or 1.6 +/- 0.1 (LH) pulses day-1. LH pulse amplitude declined (P < 0.0001) between day 4 and day 10, but FSH pulse amplitude remained large and stable, dipping slightly but not significantly on day 6. Daily mean FSH concentrations exceeded (P < 0.0001) early oestrous values between day 4 and day 5, and between day 7 and day 10. However, significantly different patterns were obtained when once-a-day sampling was simulated by selecting samples collected at 08:00 h or noon. LH was higher during the periovulatory surge than during dioestrus (P < 0.0001) and profiles were similar whether daily means or selected samples were used. It is concluded that: (1) the marked pulsatility of plasma FSH during dioestrus makes once-a-day sampling misleading for determining FSH profiles; (2) the dioestrous pattern of large, slow FSH pulses was consistent among mares, unlike that of the daily mean FSH profiles; and (3) no discrete FSH 'surges' were observed during dioestrus, although FSH pulse amplitude tended to undergo alternate increases and decreases. A period of higher amplitude FSH pulses preceded ovulation by 10.2 +/- 0.7 days, which corresponds to the approximate time the ovulatory follicle emerges. Therefore, it is possible that the signal for follicular recruitment in mares is intermittent excursions of plasma FSH above a threshold value.

Animals↗
PubMed1989

Anaerobic performances of sedentary and trained subjects.

The objective of this report was to compare the performance of sedentary individuals, physical education students, and athletes of various disciplines in 10 s and 90 s maximal cycle ergometer tests. The 10 s power was the highest power output in one second from the 10 s test, while capacities were defined as the total work output during the best 10 s trial and the 90 s test. ANOVA and Duncan multiple range test indicated that the mean values of the 10 S power and capacity and the 90 S capacity tests were significantly higher in sprinter than in sedentary groups. Sprinters performed significantly better than marathon runners only in the 10 s capacity and power. Bodybuilders and sedentary subjects had similar results in the 90 s capacity test. Mean performance values per kilogram of body weight in sedentary females reached about 60% of sedentary males while marathon runners, physical education students and sprinter females reached about 80% of the male performances for the three indicators. When expressed per kilogram of fat-free mass, females reached a higher proportion of the male values for all performances. These results indicate that: a) there are differences for the power and capacity measured in predominantly anaerobic tests between athletes from different disciplines and sedentary individuals, and b) gender differences exist for these anaerobic performance indicators, but they appear attenuated in trained subjects.

Adipose Tissue↗
PubMed1996

Waveform reliability of the phase related external suction baroreceptor manipulation method.

The phase related external suction (PRES) method of controlled carotid baroreceptor manipulation (a neck cuff with cardiac cycle timed pressure variations) has been used to investigate not only the human baroreflex, but extrahomeostatic effects of baroreceptor activity (such as the modulation of cortical activity, peripheral reflexes, and pain) as well. The present study provides quantitative within subject test-retest reliability estimates of PRES effects on 6-s trial-length heart rate waveforms. Mean within subject test-retest reliability for each averaged heart rate response waveform was 0.77 for the baroreceptor stimulation (systolic negative/diastolic positive cuff pressure) condition, 0.56 for the control condition (diastolic negative/systolic positive cuff pressure), and 0.69 for the difference between conditions. The importance of analyzing time-intensity dynamics, rather than merely the mean or maximum effect of any treatment variable is emphasized, and recommended for investigations of a wide variety of short duration, induced physiological time series processes.

Adult↗
PubMed1991

Effect of toeclip use during cycle ergometry on ventilatory threshold and VO2 max in trained cyclists and runners.

The purpose of this study was to investigate the effects of the use of toeclips on the ventilatory threshold (VT) of cyclists and runners during cycle ergometry. Ten competitive cyclists and ten well-trained runners performed two continuous maximal cycle ergometer tests, once with toeclips and once without toeclips. Respiratory data were collected every 20 s and used to determine VT and VO2 max. For cyclists, the mean (congruent to SEM) oxygen uptake at VT (VO2, VT) was greater during the trial with toeclips (48.8 +/- 1.9 ml kg-1 min-1 and 46.9 +/- 1.9 ml kg-1 min-1 during cycle ergometry with and without toeclips, respectively; p less than 0.05). No significant difference in VO2, VT was noted between trials for runners. The cyclists also demonstrated a higher VO2 max during the trial with toeclips (58.8 +/- 3.0 ml kg-1 min-1) compared to the trial without toeclips (54.4 +/- 2.0 ml kg-1 min-1; p less than 0.05). When expressed relative to VO2 max (%VO2 max) the VT during the toeclip trial for cyclists was significantly decreased (p less than 0.05). These data suggest that the cyclists in this study developed specific adaptations related to the use of toeclips, and the use of toeclips during cycle ergometry is therefore recommended. We recommend that future studies report results with VT expressed in both absolute (VO2) and relative (%VO2 max) terms.

Bicycling↗
PubMed2004

Body temperature regulation during hemodialysis in long-term patients: is it time to change dialysate temperature prescription?

During hemodialysis procedures, changes in the dialysate temperature can raise or lower body temperature because the blood is returned to the patient in thermal equilibrium with the dialysate. Even a dialysate temperature equal to the patient's body temperature as measured from the tympanic membrane, oral cavity, or axilla can result in an increase in the patient's body temperature, leading to cutaneous vasodilation and the potential for cardiovascular instability and hypotension. This deleterious cycle of events can be prevented by suitably adjusting the dialysate temperature. Lowering the dialysate temperature from 37 degrees C to 34-35.5 degrees C has improved the cardiovascular stability of many hemodialysis patients. Continuous monitoring of blood temperature allows the practitioner to make preemptive changes in dialysate temperature because a small change in body temperature can have enormous cardiovascular implications. For example, only 0.3 degrees C to 0.8 degrees C separates the thresholds for skin vasodilation from that for shivering. A suggested improvement in the hemodialysis procedure is to use devices that allow continuous monitoring of arterial and venous blood temperatures and adjust the dialysate temperature automatically, keeping the patient, not the dialysate, isothermic. Less optimal solutions appear to be (1) to monitor arterial and venous temperatures while manually adjusting the dialysate temperature to maintain arterial (and hence body) temperature stability; (2) to monitor peripheral temperatures (oral, tympanic) at regular intervals and adjust dialysate temperature to maintain the body temperature constant; (3) routinely use a dialysate temperature <37.0 degrees C in all patients unless contraindicated.

Adult↗
PubMed2001

Cytocidal effect and DNA damage of nedaplatin in vitro by simulating pharmacokinetic parameters.

PURPOSE: The pharmacodynamic effects of cis-diammine(glycolato)platinum (nedaplatin, 254-S) in vitro have been reported, but the dosage and exposure time in vitro have not always been based on clinical observations of the drug's actions in vivo. Regardless of the actual exposure conditions used, the effect of cell-cycle nonspecific anticancer agents such as nedaplatin is believed to depend on the area under the drug concentration-time curve (AUC). In this study, we evaluated the pharmacodynamics of nedaplatin in vitro, especially in relation to its AUC dependency, in terms of cell survival and DNA crosslinking. METHODS: BG-1 human ovarian cancer cells were treated with various concentrations of nedaplatin to simulate the pharmacokinetics of administration in a clinical setting. The BG-1 cells were exposed to nedaplatin dissolved in medium containing serum using constant concentration conditions, either high (maximum 7.69 mg/l) or low (average 1.33 mg/l). These concentrations were based on doses used in clinical studies. We then adjusted the exposure conditions in vitro to simulate the elimination of the drug from serum in vivo as follows: T1/2 alpha 1.20 h and T1/2 beta 2.70 h. The AUC values were set at 4, 8, 16, 25 and 40 mg.h/l for all exposure conditions. A colony-formation assay for the surviving fraction and an alkaline-elution assay for DNA crosslink measurement were done for the pharmacodynamic evaluation with comparison on the basis of the AUC value. RESULTS: Exposure to a low concentration for a long time was the most effective of the exposure conditions at the same AUC value. The greater the AUC value, the higher the crosslink index under all exposure conditions. This index tended to increase particularly after exposure to the low concentration. The natural logarithm of the surviving fraction (Y') was a linear function of the crosslink index regardless of the drug-exposure condition: ln(Y') = -87.2x + ln(5.79), R2 = 0.89. The threshold cytocidal effect was associated with a crosslink index of 0.02. CONCLUSION: There was a strong correlation between the cytocidal effect of nedaplatin and DNA crosslink formation. The cytocidal effect and DNA crosslinking in vitro depended on the exposure conditions used to define the AUC. Therefore, a new pharmacokinetic-pharmacodynamic model for nedaplatin must be constructed to investigate the most effective administration procedure in vivo.

Antineoplastic Agents↗
PubMed2002

Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest.

Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR), may be responsible for elevated intestinal temperature (T(in)) during exercise after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head-down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C). Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs. 96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs. 37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C-1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed. The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a centrally mediated elevation in the thermoregulatory set point during bed rest exposure.

Adult↗
PubMed2001

Effect of prior metabolic rate on the kinetics of oxygen uptake during moderate-intensity exercise.

Pulmonary oxygen uptake (VO2) dynamics during moderate-intensity exercise are often assumed to be dynamically linear (i.e. neither the gain nor the time constant (tau) of the response varies as a function of work rate). However, faster, slower and unchanged VO2 kinetics have been reported during work-to-work transitions compared to rest-to-work transitions, all within the moderate-intensity domain. In an attempt to resolve these discrepancies and to improve the confidence of the parameter estimation, we determined the VO2 response dynamics using the averaged response to repeated exercise bouts in seven healthy male volunteers. Each subject initially performed a ramp-incremental exercise test for the estimation of the lactate threshold (thetaL). They then performed an average of four repetitions of each of three constant-work-rate (WR) tests: (1) between 20 W and a work rate of 50% (WR50) between 20 W and 90% thetaL (step 1-->2), (2) between WR50 and 90% thetaL (step 2-->3), and (3) between 20 W and 90% thetaL (step 1-->3); 6 min was spent at each work rate increment and decrement. Parameters of the kinetic response of phase II VO2 were established by non-linear least-squares fitting techniques. The kinetics of VO2 were significantly slower at the upper reaches of the moderate-intensity domain (step 2-->3) compared to steps 1-->2 and 1-->3 [group mean (SD) phase II tau: step 1-->2 25.3 (4.9) s, step 2-->3 40.0 (7.4) s and step 1-->3 32.2 (6.9) s]. The off-transient values of tau were not significantly different from each other: 36.8 (16.3) s, 38.9 (11.6) s and 30.8 (5.7) s for steps 1-->2, 2-->3 and 1-->3, respectively. Surprisingly, the on-transient gain (G, deltaVO2/deltaWR) was also found to vary among the three steps [G = 10.56 (0.42) ml x min(-1) W(-1) 11.85 (0.64) ml x min(-1) W(-1) and 11.23 (0.52) ml x min(-1) W(-1) for steps 1-->2, 2-->3 and 1-->3, respectively]; the off-transient G did not vary significantly and was close to that for the on-transient step 1-->3 in all cases. Our results do not support a dynamically linear system model of VO2 during cycle ergometer exercise even in the moderate-intensity domain. The greater oxygen deficit per unit power increment in the higher reaches of the moderate-intensity domain necessitates a greater transient lactate contribution to the energy transfer, or a greater phosphocreatine breakdown, or possibly both.

Adult↗
PubMed2000

Real-time quantitative polymerase chain reaction. A new method that detects both the peripheral myelin protein 22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary neuropathy with liability to pressure palsies.

In Charcot-Marie-Tooth type 1A disease (CMTIA), heterozygosity for the peripheral myelin protein 22 (PMP22) duplication increases the gene dose from two to three, whereas, in hereditary neuropathy with liability to pressure palsies (HNPP), heterozygosity for the PMP22 deletion reduces the gene dose from two to one. Thirty-eight Norwegian patients with CMT1, 4 patients with HNPP, 15 asymptomatic family members, and 45 normal controls were studied using the ABI 7700 sequence detection system and the TaqMan method of real-time quantitative polymerase chain reaction (PCR). Using a comparative threshold cycle (Ct) method and albumin as reference gene, the gene copy number by PMP22 gene duplication or deletion on chromosome 17p11.2-12 was quantified. The PMP22 duplication ratio ranged from 1.50 to 2.21, the PMP22 deletion ratio ranged from 0.44 to 0.55, and the PMP22 ratio in normals ranged from 0.82 to 1.27. All samples were run in triplicate, with a mean standard deviation of 0.07 (range 0.01-0.17). Thirty-four of thirty-eight CMT1 patients (89.6%) had the PMP22 duplication and the four HNPP patients had the PMP22 deletion. This was not found in any of the asymptomatic family members or the controls. Real-time quantitative PCR is a sensitive, specific, and reproducible method for diagnosing PMP22 duplication and deletion. The method is fast, allowing 13 patients to be diagnosed in 2 h. It involves no radioisotopes and requires no post-PCR handling. In our opinion, real-time quantitative PCR is the first method of choice in diagnosing PMP22 duplication and deletion.

Charcot-Marie-Tooth Disease↗
PubMed1996

A new approach to the assessment of anaerobic metabolism: measurement of lactate in saliva.

OBJECTIVE: To test the hypothesis that saliva lactate concentrations may reflect those present in blood and that saliva lactate can be used as a very convenient and useful variable in the study of anaerobic metabolism. METHODS: Parallel determinations were made of lactate in saliva and in capillary blood samples, obtained at 3 min intervals from nine individuals during the performance of a maximum graded exercise test on a cycle ergometer against increasing workloads (from 25 up to a maximum of 300 W). Lactate determinations were done by means of an electroenzymatic method using 25 microliters samples in both types of fluids. RESULTS: For each situation, the concentration of lactate in saliva was shown to be about 15% of that in plasma but it followed the same pattern of evolution during the exercise test. A good correlation (r = 0.81) between blood and saliva lactate concentrations was found. The precision of the method was very good, with a coefficient of variation ranging (n = 10) between 2.2% for samples with very low lactate concentrations and 0.7% for sample with moderate lactate concentrations. Lactate appeared to be very stable in saliva over a period of 40 days after collection, when kept at 4 degrees C. The values obtained after this period were virtually identical to those shown in fresh samples. CONCLUSIONS: Determination of lactate in saliva can be used as an alternative to determination in blood, overcoming most of the drawbacks of the procedures being used at present, since the collection of the samples required no special expertise.

Adult↗
PubMed1984

Coupling of external to internal respiration.

Oxygen is required to generate chemical energy (ATP) to allow muscle contraction. The amount of chemical energy required is directly proportional to the work rate performed. Early in exercise, the muscle creatine phosphate and oxygen stores, primarily in the form of oxymyoglobin and oxyhemoglobin (oxygen content of venous blood decreases), are used for energy. This allows time for cardiac output and ventilation to increase to satisfy the total O2 requirement. Steady-state time depends on the level of work relative to the anaerobic threshold (AT). For work rates below the AT, steady-state for VO2 is achieved by 3 min and by 4 min for VCO2 and VE. For work rates above the AT, steady-states are considerably delayed or not achieved. For purposes of description of the pattern of external respiration (gas exchange at the lungs), three phases are defined. Phase I is the initial increase in VO2 and VCO2 at the start of exercise, lasting approximately 15 s. Because the gas exchange ratio (R) typically doesn't change during Phase I, the initial increase in VO2 and VCO2 must be due primarily to an increase in pulmonary blood flow and proportional increase in ventilation (cardiodynamic phase). Phase II is the exponential-like increase in VO2 and VCO2, which follow Phase I and terminates in a steady-state or asymptotic value (Phase III). At moderate work, VO2 increases more rapidly than VCO2 during Phase II (CO2 stores increase). Therefore, R decreases before it increases to the steady-state. Below the AT, the rate of external respiration equals the rate of internal respiration during Phase III.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗
PubMed1995

A note on the cellular effects of nystatin in single myoballs.

Volume changes in single L6 myoblasts (myoballs) exposed to nystatin solutions were followed on single cell level by means of quantitative video image analysis. The myoblasts swelled in nystatin solutions. The volume change was dependent on the nystatin concentration, the threshold concentration being 12.5 mumol/l of nystatin freshly dissolved in Krebs solution. The threshold effect was triphasic: a slight initial volume decrease (shrinkage) for about 2 min followed by a volume increase and, after about 10 min by a significant volume decrease. At twice as high nystatin concentration (25 mumol/l) the final shrinkage phase was lacking. At 50 mumol/l concentration the volume increased continually after a delay of about 1-2 min. and reached a plateau of about 350% of the original volume. At 100 mumol/l concentration of nystatin the myoblasts increased their volume in about five min to more than 500% of the original value. The effects of nystatin diminished upon prolonged storage of nystatin Krebs solution. Nystatin solutions (50 mumol/l) prepared 3 hours before use were stil active to about 80%. Volume changes in 100 mumol/l nystatin solutions were, however, substantially diminished (to about 20%) 5 hours after the preparation of the nystatin solution. By replacing external Na+ by TEA+ in the presence of external Cl- a regulatory volume decrease was observed to subnormal values; the myoblast volume shrank to about half of the control value. The volume changes were reversible after reintroduction of Krebs solution. The regulatory volume decrease to subnormal values was also observed after replacing external Cl- by glutamate anion in the presence of external Na. The volume changes were, however, not reversible after reintroduction of Krebs solution. The swelling of myoblasts in 50 mumol/l nystatin Krebs solution continued after a definite enlargement of the whole myoblast was reached with the formation of several blebs, which eventually coalesced to form a continuous layer around the myoballs. The enlarged vesicles in nystatin solutions were able to start and fulfill the mitotic cycle. Cell volume measurements represent a handy means for checking the activity of nystatin solutions for the perforated patch experiments.

Animals↗
PubMed1999

Attenuation of conduction delay by ischemic preconditioning reduces ischemia-induced ventricular arrhythmias.

Ischemic preconditioning has been acknowledged as a powerful method of decreasing ischemic injury. However, the antiarrhythmic mechanism of ischemic preconditioning during ischemia is unclear. We studied the effects of ischemic preconditioning on arrhythmias and cardiac electrophysiology during ischemia in Langendorff rat hearts (n = 44). In the non-preconditioned group (PC(-); n = 24), the hearts underwent 5-min zero-flow global ischemia without any prior ischemic preconditioning. In the preconditioned group (PC(+); n = 20), the hearts were preconditioned by three cycles of 3-min zero-flow global ischemia and 5-min reperfusion before undergoing 5-min global ischemia. Ischemic preconditioning reduced the incidence of ischemia-induced arrhythmias (PC(-); 38.9%, PC(+): 8.3%, p < 0.05), shortened monophasic action potential duration (MAPD, P < 0.05), attenuated conduction delay (conduction time; PC(-): 234.2%, PC(+): 173.4%, P < 0.05) and increased the ventricular fibrillation threshold. Although the shortening of MAPD in PC(-) hearts was not influenced by the presence or absence of arrhythmias, conduction time prolongation at 3-min was more obvious in PC(-) hearts with arrhythmia than in PC(-) hearts without arrhythmia (PC(-) with arrhythmia: 220.2%, PC(-) without arrhythmia: 190.7%, P < 0.05). We concluded that ischemic preconditioning could protect the rat hearts from ischemia-induced arrhythmias and postulated that attenuation of conduction delay during ischemia might be an important factor in the antiarrhythmic action of ischemic preconditioning.

Action Potentials↗
PubMed2006

Modeling and cost-effectiveness analysis of etanercept in adults with rheumatoid arthritis in Japan: a preliminary analysis.

The tumor necrosis factor (TNF) antagonist etanercept is an antirheumatic agent which was approved by Japanese regulatory authorities in January 2005. In Japan, the cost-effectiveness of this therapy for patients with rheumatoid arthritis (RA) has not previously been evaluated. This study models the cost-utility of etanercept in comparison with standard therapy with disease-modifying antirheumatic drugs (DMARDs) among adult Japanese RA patients who have failed a previous course of the DMARD bucillamine. A Markov model with 6-month cycles was constructed to compare two therapeutic strategies: etanercept versus standard therapy. For each cycle, one of three options was possible: a patient could (i) remain on current therapy if American College of Rheumatology criteria for 20% clinical improvement (ACR20) were achieved, (ii) switch to another drug in the therapeutic pathway if ACR20 was not achieved or if side effects severe enough to cause treatment discontinuation occurred, or (iii) they could die. The therapeutic pathway for the etanercept strategy was etanercept, methotrexate (MTX), sulfasalazine (SSZ), combination therapy (MTX + SSZ) and, finally, no DMARD. The pathway for standard therapy was identical except the initial therapy was MTX (etanercept was excluded). Results from clinical trials in U.S. and European patient populations were used to derive model probabilities for disease progression, response to drug therapy, and relationships between ACR20 response and functional improvement as measured by the Health Assessment Questionnaire (HAQ) disability index. An equation was developed to predict utility from HAQ scores of Japanese patients. Costs for drugs and medical services in Japan were obtained for April 2003. Analysis was conducted from a societal perspective, including lost productivity costs due to RA disability and premature mortality. Costs were discounted at 6% annually, and quality-adjusted life years (QALYs) at 1.5% annually. Model parameters were varied by 20% above and below base-case values in sensitivity analyses. Compared to standard therapy, the etanercept strategy was yen6.39 million more costly per patient but yielded an additional 2.56 QALYs. The incremental cost-utility ratio was yen 2.50 million/QALY. Sensitivity analyses revealed that cost-utility was most strongly influenced by the acquisition cost of etanercept and the percentage of etanercept recipients who achieved ACR20. Using commonly applied thresholds for acceptable cost-effectiveness in the United States ($50 000 = yen 5.5 million/QALY) and the United Kingdom (pound 30 000 = yen 5.7 million/QALY), etanercept therapy in Japan can be considered cost-effective. Cost-utility ratios did not exceed these thresholds in any sensitivity analysis. Further analyses should be conducted once clinical and epidemiologic data for Japanese patients become available.

Antirheumatic Agents↗
PubMed1994

A method for determining the maximal steady state of blood lactate concentration from two levels of submaximal exercise.

The aim of this study was to estimate the characteristic exercise intensity (WCL) which produces the maximal steady state of blood lactate concentration (MLSS) from submaximal intensities of 20 min carried out on the same day and separated by 40 min. Ten fit male adults [maximal oxygen uptake (VO2max) 62 (SD 7) ml.min-1.kg-1] exercised for two 30-min periods on a cycle ergometer at 67% (test 1.1) and 82% of VO2max (test 1.2) separated by 40 min. They exercised 4 days later for 30 min at 82% of VO2max without prior exercise (test 2). Blood lactate was collected for determination of lactic acid concentration every 5 min and heart rate and O2 uptake (VO2) were measured every 30 s. There were no significant differences at the 5th, 10th, 15th, 20th, 25th, or 30th min between VO2, lactacidaemia, and heart rate during tests 1.2 and 2. Moreover, we compared the exercise intensities (WCL) which produced the MLSS obtained during tests 1.1 and 1.2 or during tests 1.1 and 2 calculated from differential values of lactic acid blood concentration ([la-]b) between the 30th and the 5th min or between the 20th and the 5th min. There was no significant difference between the different values of WCL [68 (SD 9), 71 (SD 7, 73 (SD 6), 71 (SD 11)% of VO2max] (ANOVA test, P < 0.05). Four subjects ran for 60 min at their WCL determined from periods performed on the same day (test 1.1 and 1.2) and the difference between the [la-]b at 5 min and at 20 min (delta ([la-]b)) was computed.(ABSTRACT TRUNCATED AT 250 WORDS)

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