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Which common NIRS variable reflects muscle estimated lactate threshold most closely?

Various near-infrared spectroscopy (NIRS) variables have been used to estimate muscle lactate threshold (LT), but no study has determined which common NIRS variable best reflects muscle estimated LT. Establishing the inflection point of 2 regression lines for deoxyhaemoglobin (DeltaHHb(i.p).), oxyhaemoglobin (DeltaO2Hb(i.p.)), and tissue oxygenation index (TOIi.p.), as well as for blood lactate concentration, we then investigated the relationships between NIRS variables and ventilatory threshold (VT), LT, or maximal tissue hemoglobin index (nTHImax) during incremental cycling exercise. DeltaHHb(i.p.) and TOI(i.p.) could be determined for all 15 subjects, but DeltaO2Hb(i.p.) was determined for only 11 subjects. The mean absolute values for the 2 measurable slopes of the 2 continuous linear regression lines exhibited increased changes in 3 NIRS variables. The workload and VO2 at DeltaO2Hb(i.p.) and nTHImax were greater than those at VT, LT, DeltaHHb(i.p.), and TOI(i.p.). For workload and VO2, DeltaHHb(i.p.) was correlated with VT and LT, whereas DeltaO2Hb(i.p.) was correlated with nTHImax, and TOI(i.p.) with VT and nTHImax. These findings indicate that DeltaO2Hb strongly corresponds with local perfusion, and TOI corresponds with both local perfusion and deoxygenation, but that DeltaHHb can exactly determine deoxygenation changes and reflect O2 metabolic dynamics. The finding of strongest correlations between DeltaHHb and VT or LT indicates that DeltaHHb is the best variable for muscle LT estimation.

Adult↗

Peripheral muscle weakness and exercise capacity in children with cystic fibrosis.

Exercise intolerance in cystic fibrosis (CF) is attributed to diminished nutritional and pulmonary function. We studied the pathophysiology of such intolerance in relation to muscle force and fat-free mass (FFM), in 15 children with moderately severe symptoms of CF (FEV1 < 80% predicted and/or weight for age < -1 SD of reference median), 13 children with mild symptoms of CF (FEV1 and weight above these thresholds), and 13 healthy controls. Cycle maximal workload (Wmax) and V O2max were assessed. Maximal peripheral muscle force was measured, and FFM was calculated from skinfolds. Patients with mild CF, as compared with matched controls, had lower values of Wmax per kilogram of FFM (3.9 +/- 0.5 versus 4.6 +/- 0.3 W/kg [mean +/- SD], respectively; difference = 0.7 [95% CI = 0.4 to 1.1]), and diminished maximal muscle force (2.7 +/- 0.4 kN versus 3.1 +/- 0.7 kN; difference = 0.44 [95% CI = 0.03 to 0.87]), but similar V O2max. Patients with moderate CF had lower FFM, muscle force, and exercise tolerance than did the other groups. Oxygen cost of work was elevated in both groups of CF patients. Muscle force showed a strong positive correlation with Wmax in patients and controls, with disproportionately lower regression slopes in the CF patients. In children with CF, muscle force is decreased and associated with diminished maximal work load, even in the absence of diminished pulmonary or nutritional status.

Adolescent↗

Cell cycle-related expression of p120 nucleolar antigen in normal human lymphocytes and in cells of HL-60 and MOLT-4 leukemic lines: effects of methotrexate, camptothecin, and teniposide.

Expression of the proliferation-associated nucleolar antigen p120 was studied by flow cytometry in human quiescent and phytohemagglutinin-stimulated lymphocytes, as well as in human lymphocytic (MOLT-4) and promyelocytic (HL-60) cell lines. Bivariate analysis of p120 and DNA content made it possible to correlate p120 expression with cell position in the cycle. Proliferating lymphocytes and MOLT-4 and HL-60 cells had a similar pattern of p120 expression. Populations of G1 cells, in all three cell types, were very heterogenous with respect to p120, and a threshold in G1 was observed. The cells with a p120 level below the threshold value did not enter S phase. An increase in p120 was observed during progression through S phase, and the antigen was maximally expressed in G2 cells. The p120/DNA content ratio, however, was highest in late G1 cells (G1B) and was declining during S and G2. The data thus suggest that p120 may be degraded during mitosis and that the postmitotic cells inherit little, if any, of this protein; the antigen then accumulates predominantly during G1, and must reach a threshold level to enable the cells to enter S phase. Antigen p120 could not be detected in noncycling lymphocytes nor in HL-60 cells induced to myeloid differentiation by growth in the presence of dimethyl sulfoxide. Treatment of MOLT-4 cells with pharmacological concentrations of methotrexate, camptothecin, or teniposide induced cell arrest in S or G2; expression of p120 in the arrested cells was unchanged from that of untreated MOLT-4 controls at the same phase of the cycle. The level of p120 was minimal in MOLT-4 or HL-60 cells arrested in M phase by vinblastine, but vinblastine had no effect on p120 fluorescence of interphase cells. Camptothecin or teniposide induced apoptosis selectively in S phase of HL-60 cells; apoptotic cells from camptothecin-treated cultures, however, despite the marked nucleolysis, still expressed p120. The data on the drug-treated cells indicate that the p120 level in tumors of patients may be used as a marker of tumor/malignancy even in clinical samples obtained during treatment.

Antigens, Neoplasm↗

Peak oxygen consumption and ventilatory thresholds on six modes of exercise.

In order to compare responses on six modes of exercise for maximal oxygen consumption (VO2peak) and ventilatory thresholds (VT-1, VT-2), 10 male recreational exercisers (23 +/- 3 yrs) completed incremental maximal tests on treadmill, stationary skier, shuffle skier, stepper, stationary cycle, and rower. After extensive habituation, VO2peak, VT-1, and VT-2 were determined during each maximal bout. A MANOVA followed by ANOVAs, Tukey post hoc tests, and noncentral F tests indicated that the treadmill elicited a significantly higher peak oxygen consumption than did the other modes, and the skier and stepper values were higher than the rower. VO2 at VT-1 was higher on the treadmill than cycle. The treadmill also elicited a higher VO2 at VT-2 than the shuffle skier, cycle, and rower. However, no differences were observed among modes for VT-1 and VT-2 when expressed as a percentage of VO2peak. These results suggest that the treadmill elicits a higher aerobic capacity measure than other modes, but the ventilatory threshold responses (% VO2peak) are similar among modes.

Adult↗

Predicting continuous values of prognostic markers in breast cancer from microarray gene expression profiles.

The prognostic and treatment-predictive markers currently in use for breast cancer are commonly based on the protein levels of individual genes (e.g., steroid receptors) or aspects of the tumor phenotype, such as histological grade and percentage of cells in the DNA synthesis phase of the cell cycle. Microarrays have previously been used to classify binary classes in breast cancer such as estrogen receptor (ER)-alpha status. To test whether the properties and specific values of conventional prognostic markers are encoded within tumor gene expression profiles, we have analyzed 48 well-characterized primary tumors from lymph node-negative breast cancer patients using 6728-element cDNA microarrays. In the present study, we used artificial neural networks trained with tumor gene expression data to predict the ER protein values on a continuous scale. Furthermore, we determined a gene expression profile-directed threshold for ER protein level to redefine the cutoff between ER-positive and ER-negative classes that may be more biologically relevant. With a similar approach, we studied the prediction of other prognostic parameters such as percentage cells in the S phase of the cell cycle (SPF), histological grade, DNA ploidy status, and progesterone receptor status. Interestingly, there was a consistent reciprocal relationship in expression levels of the genes important for both ER and SPF prediction. This and similar studies may be used to increase our understanding of the biology underlying these markers as well as to improve the currently available prognostic markers for breast cancer.

Biomarkers↗

Muscle oxygenation trends during dynamic exercise measured by near infrared spectroscopy.

During the last decade, NIRS has been used extensively to evaluate the changes in muscle oxygenation and blood volume during a variety of exercise modes. The important findings from this research are as follows: (a) There is a strong correlation between the lactate (ventilatory) threshold during incremental cycle exercise and the exaggerated reduction in muscle oxygenation measured by NIRS. (b) The delay in steady-state oxygen uptake during constant work rate exercise at intensities above the lactate/ventilatory threshold is closely related to changes in muscle oxygenation measured by NIRS. (c) The degree of muscle deoxygenation at the same absolute oxygen uptake is significantly lower in older persons compared younger persons; however, these changes are negated when muscle oxygenation is expressed relative to maximal oxygen uptake values. (d) There is no significant difference between the rate of biceps brachii and vastus lateralis deoxygenation during arm cranking and leg cycling exercise, respectively, in males and females. (e) Muscle deoxygenation trends recorded during short duration, high-intensity exercise such as the Wingate test indicate that there is a substantial degree of aerobic metabolism during such exercise. Recent studies that have used NIRS at multiple sites, such as brain and muscle tissue, provide useful information pertaining to the regional changes in oxygen availability in these tissues during dynamic exercise.

Adipose Tissue↗

Effects of chemical stimulation of masseter muscle nociceptors on trigeminal motoneuron and interneuron activities during fictive mastication in the rabbit.

An electrophysiological study was carried out in sixteen decerebrate and paralyzed New Zealand rabbits to determine how a bolus injection of a nociceptor stimulant (hypertonic saline, 5%) into the masseter muscle influences the activity of the trigeminal motor circuitry during fictive jaw movements. Hypodermic needles connected to a syringe held in a computer-controlled infusion pump were inserted into the anterior deep layer of either the right or the left masseter. Twenty-three infusions of 50, 70 or 80 microl saline were made in fourteen animals at constant rates over 1 min. Eight control infusions of normal saline (0.9%) were made in a subpopulation of five animals in an identical manner. Fictive jaw movements were evoked before and after the infusions by repetitive electrical stimulation of the corticobulbar tract. Effects were assessed by extracellular microelectrode recordings made from the digastric motoneuron pool and from putative last-order interneurons in the oral subnucleus of the spinal trigeminal tract and adjacent structures. In comparison with pre-infusion control cycles, nociceptor stimulation caused significant slowing of the rhythm and a reduction of the area of the digastric motoneuron bursts in the majority of the animals (12/14). The decrease in cycle frequency was due almost entirely to a lengthening of the time between the digastric bursts. Changes usually began 1-2 min after the infusion and returned to pre-infusion values within 10-15 min. No significant effects were seen when isotonic saline was applied. Recordings were obtained from nine interneurons, eight of which had low threshold mechanosensitive receptive fields. One neuron was, in addition, excited by pinch. Eight were not active in the absence of motor activity and this did not change when hypertonic saline was applied. However, once fictive movements began, all started to fire rhythmic bursts of spikes. In five cases, there was a significant post-infusion increase in spike frequency, and three showed decreases. Seven showed significant post-infusion changes in mean phase and/or concentration of their firing within the movement cycle. Changes in the preferred phase of interneuronal firing were significantly correlated to changes in the phase of offset of the digastric burst. The present results provide evidence that the stimulation of nociceptors in a muscle slows the frequency of rhythmical movements in the absence of sensory feedback. They confirm that infusions into one muscle affect the output of its antagonist. The results also suggest that neurons in the oral subnucleus of the spinal trigeminal tract and adjacent reticular formation appear to participate in programming these changes in motor output.

Animals↗

Effect of training on the rating of perceived exertion at the ventilatory threshold.

The purpose of this study was to determine the effect of training on the rating of perceived exertion (RPE) at the ventilatory threshold. College students were assigned to either training (n = 17) or control (n = 10) groups. Trainers completed 18 interval training sessions (five X 5 min cycling at 90-100% VO2max) and 8 continuous training sessions (40 min running or cycling) in 6 weeks. Pre- and post-training, cardiorespiratory, metabolic, and perceptual variables were measured at the ventilatory threshold during graded exercise tests on a cycle ergometer. Ventilatory threshold was that point above which VE X VO2-1 increased abruptly relative to work rate. Post-training means of trained and control subjects were compared using analysis of covariance, with pre-training values as covariates. Following training, the adjusted means for the trained subjects were significantly greater (p less than 0.05) than for controls for VO2max (6%), and for work rate (20%), VO2 (23%), and %VO2max (13%) at the ventilatory threshold. However, adjusted means for RPE at the ventilatory threshold were not significantly different (2%). Both before and after training, exercise at the ventilatory threshold was perceived as 'somewhat hard' to 'hard' (RPE = 13-15) by both groups. The relationship between RPE and %VO2max was altered by training, with trained subjects having a lower RPE at a given %VO2max. It is concluded that RPE at the ventilatory threshold is not affected by training, despite that after training the ventilatory threshold occurs at a higher work rate and is associated with higher absolute and relative metabolic and cardiorespiratory demands.

Adult↗

Origin, cellular expression, and cybrid transmission of mitochondrial CAP-R, PYR-IND, and OLI-R mutant phenotypes.

Chloramphenicol-resistant (CAP-R) mouse and Chinese hamster lines were isolated in a single selection step in drug medium containing pyruvate. Cellular expression of the CAP-R phenotype required pyruvate--or an appropriate substitute--as a nutritional supplement. Subclone lines which were pyruvate independent (PYR-IND) arose in second-step selections at a high frequency. CAP-R PYR-IND Chinese hamster mutants could be directly isolated in single-step selections but at a very low frequency. Subclone lines (OLI-R) which were cross-resistant to oligomycin were isolated in a third selection cycle. The PYR-IND and OLI-R phenotypes were cotransmitted with the CAP-R mtDNA mutation but were expressed at the cellular level only if the number of mutant mitochondrial genomes exceeded a minimum threshold value. Analysis of a mtDNA restriction fragment alteration in one series of mutants supported this model. Threshold limits for cellular expression of mitochondrial mutant phenotypes are likely to be a general phenomenon and will constrain models of the origin and segregation of mtDNA mutations.

Animals↗

Urogenital re-education by electrostimulation: modelling for minimum energy computation.

The analysis of the voltage curve V(t) picked up between the two electrodes of a vaginal plug used with a current source stimulation allowed us to suggest a simple electrical model for intravaginal tissue. It is made up of three cells in series: a resistor in parallel with a capacitor for the first two, and a simple resistor for the third. Measurements throughout the hormonal cycle exhibit large variations in resistance and capacitance, and justify the use of a current source device to keep reproducible conditions of stimulation. Subjective detection of sensitivity threshold currents shows results which are independent of the day in the cycle and thus confirms the use of current source stimulation. The curve representing dissipated energy as a function of the pulse duration tau exhibits a minimum value different from the chronaxie (here 800 microseconds). The minimum value is effectively obtained at lower values of tau between 450 and 500 microseconds, dependent on the day of the cycle and the electrical characteristics of vaginal tissue. Two values of tau (230 and 1000 microseconds) between which the energy dissipated is less than Emin + 10 per cent are determined. This gap of pulse duration seems to be a correct range according to the minimum energy criterion for electrostimulation applied to urogenital re-education.

Electric Impedance↗

Muscle activation during cycling at different cadences: effect of maximal strength capacity.

The purpose of this study was to examine the influence of maximal strength capacity on muscle activation, during cycling, at three selected cadences: a low cadence (50 rpm), a high cadence (110 rpm) and the freely chosen cadence (FCC). Two groups of trained cyclists were selected on the basis of the different maximal isokinetic voluntary contraction values (MVCi) of their lower extremity muscles as follow: F(min) (lower MVCi group) and F(max) (higher MVCi group). All subjects performed three 4-min cycling exercises at a power output corresponding to 80% of the ventilatory threshold under the three cadences. Neuromuscular activity of vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF) was studied quantitatively (integrated electromyography, IEMG) and qualitatively (timing of muscle bursts during crank cycle). Cadence effects were observed on the EMG activity of VL muscle and on the burst onset of the BF, VL and RF muscles. A greater normalized EMG activity of VL muscle was observed for the F(min) group than the F(max) group at all cadences (respectively F(min) vs. F(max) at 50 rpm: 17+/-5% vs. 38+/-6%, FCC: 22+/-7% vs. 44+/-5% and 110 rpm: 21+/-6% vs. 45+/-6%). At FCC and 110 rpm, the burst onset of BF and RF muscles of the F(max) group started earlier in the crank cycle than the F(min) group These results indicate that in addition to the cadence, the maximal strength capacity influences the lower extremity muscular activity during cycling.

Adult↗

Effects of L- and DL-carnitine on patients with impaired exercise tolerance.

We designed this study to determine whether orally administered L- and DL-carnitine can improve exercise tolerance in a group of patients with exercise intolerance. Nineteen patients with cardiac disease were randomly divided into 2 groups, an L-carnitine treatment group (n = 9) and a DL-carnitine treatment group (n = 10). Eight additional age-matched patients served as an untreated control group. Subjects in both carnitine treatment groups underwent cardiopulmonary exercise testing on a cycle ergometer in order to determine peak exercise time, peak oxygen uptake (VO2), lactate threshold (LT) and ventilatory threshold (VT) before and after the oral administration of 900 mg/day of L- or DL-carnitine for 2 weeks. Basal values of peak exercise time, peak VO2, LT and VT did not differ significantly among the 3 groups. Peak exercise time and peak VO2 tended to be increased in the L-carnitine treatment group, and tended to be decreased in the DL-carnitine treatment group. Both LT and VT (ml/kg/min) were significantly improved (LT: from 9.7 +/- 0.6 to 10.8 +/- 1.0, p < 0.05; VT: from 9.8 +/- 0.8 to 11.8 +/- 1.9, p < 0.02) by the administration of L-carnitine, while LT was significantly decreased (from 11.0 +/- 2.0 to 9.6 +/- 1.2, p < 0.05) and VT tended to be decreased by the administration of DL-carnitine (from 11.6 +/- 2.0 to 10.8 +/- 2.4). In the untreated control group, no significant changes were observed in the values of exercise tolerance between the 2 series of exercise testings. In neither group did carnitine modify hemodynamic parameters at rest or during exercise. In conclusion, this study demonstrated that L-carnitine increases and DL-carnitine decreases exercise tolerance in patients with impaired exercise tolerance.

Administration, Oral↗

Synergistic effect of low-frequency ultrasound and sodium lauryl sulfate on transdermal transport.

Application of low-frequency ultrasound has been shown to enhance transdermal transport of drugs (low-frequency sonophoresis). In this paper, we show that the efficacy of low-frequency ultrasound in enhancing transdermal transport can be further increased by its combination with sodium lauryl sulfate (SLS), a well-known surfactant. The dependence of the ultrasound-SLS-mediated transport on ultrasound parameters, including intensity, net exposure time, and duty cycle, is discussed. The transdermal transport enhancement is proportional to ultrasound intensity as well as to exposure time, and is independent of duty cycle as long as the net exposure time is the same. The synergistic effect of SLS and ultrasound on transdermal transport increases linearly with SLS concentration. The enhancement is also proportional to the ultrasound energy density beyond a threshold value, which suggests that a certain minimum amount of energy density is required before noticeable changes in skin permeability occur. A similar dependence of the transdermal transport enhancement on energy density is observed in the case of the enhancement induced by ultrasound alone. Although the threshold energy density value in the presence of SLS is about 10 times lower than that in the case of ultrasound alone, the relationship between enhancement and energy density in the presence and in the absence of SLS is otherwise similar. Possible mechanisms for the synergistic effect of ultrasound and SLS are also discussed.

Aluminum↗

Entrainment mapping in patients with sustained atrioventricular nodal reentrant tachycardia: insights into the sites of conduction slowing in the slow atrioventricular nodal pathway.

The inferoposterior region of the triangle of Koch is hypothesized to be the location of the atrial insertion of the slow atrioventricular (AV) nodal pathway. However, the actual site of conduction slowing in the slow AV nodal pathway is unknown. Entrainment mapping during AV nodal reentry can localize the reentrant pathway as follows: the AH interval measured from the mapping catheter = A'H (where A' is the exit site of the reentrant circuit) minus A'A (the conduction time from A' to the site of mapping); the SH interval during entrainment = SA' (the conduction time from stimulus into the reentry circuit) plus A'H. Thus, in all cases, the SH interval should be greater than or equal to the AH interval, and the deltaAH-SH should increase as distance and conduction time (SA' and A'A) from the reentry circuit increases. Fourteen patients with typical AV nodal reentry (cycle length 346 +/- 62 ms) and 1 with fast-slow (cycle length 430 ms) underwent activation and entrainment mapping from 8 to 12 sites in the triangle of Koch and coronary sinus. Pacing was performed at 2 to 3 mA above threshold, at a cycle length 10 ms shorter than tachycardia. A mapping site was defined as being in close proximity to the circuit if the deltaAH-SH was within 120% of the shortest 20th percentile deltaAH-SH value from all measured sites. In the 14 typical cases, 45 of 83 sites (54%) in the anatomic slow pathway region fulfilled criteria for close proximity to the reentry circuit compared with 13 of 50 sites (26%) outside of this region (p = 0.005). For these patients, the shortest SH interval measured from any entrainment site was 294 +/- 58 ms (89 +/- 10% of tachycardia cycle length, range 70% to 119%), indicating that the site of slow conduction in the slow pathway during AV nodal reentrant tachycardia was distal to all mapped sites. Thus, during typical AV nodal reentry, the "slow" pathway does not conduct slowly, and its insertion is located at or within the inferoposterior or midseptal regions in most cases.

Adult↗

Modulation of pacemaker activity of sinoatrial node cells by electrical load imposed by an atrial cell model.

To investigate the electrotonic modulation of sinoatrial (SA) node pacemaker activity by atrial muscle, single or multiple (2-7) SA node cells isolated from rabbit hearts were connected to a membrane model [resistance-capacitance (R-C) circuit] of an atrial cell through an external circuit that mimics the gap junctional conductance (Gc) between cells. When Gc was 0 nS (uncoupled conditions), all the preparations generated regular and stable spontaneous action potentials with a mean cycle length (SCL) of 263 +/- 45 ms (+/- SD, n = 35). Step increases of Gc were associated with a progressive prolongation of SCL. At sufficiently high values of Gc, the spontaneous activity became irregular and finally stopped. We defined the threshold Gc causing an appreciable SCL irregularity as the minimum Gc at which the ratio of SD to mean of SCL was > 0.3. The threshold Gc for a single SA node cell was calculated to be 0.58 nS. In the presence of acetylcholine (ACh; 0.05-0.2 microM), the coupling-induced inhibition of spontaneous activity was greatly increased, and the threshold Gc for a single SA node cell was decreased in a concentration-dependent manner. These findings show that the pacemaker activity of SA node cells is easily inhibited when the cells are coupled to a passive atrial cell model and the inhibition is amplified by ACh. Computer simulation using a modified Oxsoft HEART model indicates that the passive atrial cell model acts as a current sink, imposing a substantial outward current on the SA node cell, and ACh amplifies the effect by activating an additional outward current.

Acetylcholine↗

Chronopharmacological study of sodium valproate in mice: dose-concentration-response relationship.

Effects of the time-of-day of drug administration on the pharmacokinetics electroshock seizure (ES) threshold and acute toxicity were investigated in mice with sodium valproate (VPA). ICR male mice, housed under a light-dark (12:12) cycle, were orally administered 600 mg/kg VPA for anticonvulsant effect studies and administered 1500 mg/kg VPA for acute toxicity studies. A significant circadian rhythm was demonstrated for the ES threshold at 30 min after VPA administration, with the highest value in the light phase and the lowest in the dark phase, although no rhythm was shown in the nondrugged state. A significant circadian rhythm was also shown for plasma and brain VPA concentrations. This finding nicely corresponded to the circadian rhythm in the ES threshold. The positive relationship between the brain VPA concentration and the ES threshold was not different between the light phase and the dark phase. There was also a significant circadian rhythm in the acute toxicity induced by VPA, with the highest mortality in the light phase and the lowest in the dark phase. The results suggest the importance of time in the circadian stage at which VPA is administered in the experimental studies in mice and the significance of circadian rhythm in VPA kinetics in relation to the rhythm of ES threshold.

Animals↗

Flow cytometric analysis of phosphorylated histone H2AX following exposure to ionizing radiation in human microvascular endothelial cells.

We applied a flow cytometric method to quantify IR-induced histone H2AX phosphorylation at serine 139 (gammaH2AX) and compared those values to those obtained using a standard microscopy based foci counting method. After PFA fixation, methanol permeabilization was suitable for both FITC- or Alexa647-gammaH2AX. In contrast, Alexa647-gammaH2AX was not suitable for ethanol permeabilization. Antibody concentrations at 1-2 microg/ml yielded the highest gammaH2AX positive percentage for both antibodies. Without DAPI staining, gammaH2AX formation can be measured as a relative fold increase. Values determined by bivariant flow cytometric analysis and those obtained using microscopic foci formation exhibited a good quantitative correlation. Values obtained by both methods could vary according to the gating or threshold setting used. gammaH2AX positive cells increased as a function of radiation dose (2-16 Gy) followed by a dose-dependent decay. The free radical scavenger N-acetyl-L-cysteine (NAC), if administered at a concentration of 4 mM 30 min before IR, was effective in reducing IR-induced gammaH2AX formation in all phases of the cell cycle. We have developed a simplified and quantitative flow cytometry based method to measure IR-induced gammaH2AX in cells and demonstrated strong correlation to values obtained by a standard automated digital microscopic foci analysis along with NIH ImageJ custom macro software.

Cells, Cultured↗

A simplified strategy for the estimation of the exercise ventilatory thresholds.

PURPOSE: To analyze the limits of agreement between exercise ventilatory threshold values (VT1 and VT2) estimated from a combination of pulmonary gas exchange and ventilatory variables (cardiopulmonary exercise testing) and those derived from an alternative approach based on the ventilatory response only (V(E), ventilometry). METHODS: Forty-two nontrained subjects (24 males, aged 18-48, peak VO(2) = 33.1 +/- 8.6 mL.min(-1).kg(-1)) performed a maximum incremental cardiopulmonary exercise testing on an electromagnetically braked cycle ergometer. The participants breathed through a Pitot tube (Cardio2 System, MGC) and a fixed-resistance ventilometer (Micromed, Brazil), which were connected in series. HR values at the estimated VT (VTHR1 and VTHR2) were obtained by the conventional method (ventilatory equivalents, end-expiratory pressures for O(2) and CO(2), and the V-slope procedure) and an experimental approach (V(E) vs time, V(E)/time vs time, and breathing frequency vs time). RESULTS: There were no significant between-method differences on VT(HR1), VT(HR2), VT(VE1), VT(VE2), and peak V(E) (P > 0.05). After certification of data normality, a Bland-Altman analysis revealed that the mean bias +/- 95% confidence interval of the between-method differences were lower for VT(HR2) than VT(HR1) (2 +/- 9 and 0 +/- 17 bpm, respectively). VT(HR2) according to ventilometry differed more than 10 bpm from the standard procedure in 3 out of 42 subjects (9%). Between-method differences were independent of the level of fitness, as estimated from peak VO(2) (P > 0.05). CONCLUSIONS: : A simplified approach, based on the ventilatory response as a function of time, can provide acceptable estimates of the exercise ventilatory thresholds--especially VT2--during ramp-incremental cycle ergometry. This new strategy might prove to be useful for exercise training prescription in nontrained adults.

Adolescent↗