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PubMed2003

A proximal femoral implant preserves physiological bone deformation: a biomechanical investigation in cadaveric bones.

The aim of this study was to compare the perturbances in bone deformation patterns of the proximal femur due to a conventional cemented femoral stem and a novel uncemented implant designed on the principles of osseointegration. Five matched pairs of fresh frozen human femora were mechanically tested. Bone deformation patterns, measured with a video digitizing system under 1.5 kN joint force, showed that the cemented Spectron femoral implant caused significant alterations to the proximal femoral deformation pattern, whereas the Gothenburg osseointegrated titanium femoral implant did not significantly alter the bone behaviour (p < 0.05). Vertical micromotions measured under 1 kN after 1000 cycles were within the threshold of movement tolerable for bone ingrowth (21 microm for the Gothenburg system and 26 microm for the cemented implant).

Biomechanical Phenomena↗
PubMed1985

Effects of training at and above the lactate threshold on the lactate threshold and maximal oxygen uptake.

Thirty-three college women (mean age = 21.8 years) participated in a 5 d X wk-1, 12 week training program. Subjects were randomly assigned to 3 groups, above lactate threshold (greater than LT) (N = 11; trained at 69 watts above the workload associated with LT), = LT (N = 12; trained at the work load associated with LT) and control (C) (N = 10). Subjects were assessed for VO2max, VO2LT, VO2LT/VO2max, before and after training, using a discontinuous 3 min incremental (starting at 0 watts increasing 34 watts each work load) protocol on a cycle ergometer (Monark). Respiratory gas exchange measures were determined using standard open circuit spirometry while LT was determined from blood samples taken immediately following each work load from an indwelling venous catheter located in the back of a heated hand. Body composition parameters were determined before and after training via hydrostatic weighing. Training work loads were equated so that each subject expended approximately 1465 kJ per training session (Monark cycle ergometer) regardless of training intensity. Pretraining, no significant differences existed between groups for any variable. Post training the greater than LT group had significantly higher VO2max (13%), VO2LT (47%) and VO2LT/VO2max (33%) values as compared to C (p less than .05). Within group comparisons revealed that none of the groups significantly changed VO2max as a result of training, only the greater than LT group showed a significant increase in VO2LT (48%) (p less than .05), while both the = LT and greater than LT group showed significant increases in VO2LT/VO2max (= LT 16%, greater than LT 42% (p less than .05)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

The continuous Prisoner's dilemma: II. Linear reactive strategies with noise.

We present a general model for the Continuous Prisoner's Dilemma and study the effect of errors. We find that cooperative strategies that can resist invasion by defectors are optimistic (make high initial offers), generous (always offer more cooperation than the partner did in the previous round) and uncompromising (offer full cooperation only if the partner does). A necessary condition for the emergence of cooperation in the continuous Prisoner's Dilemma with noise is b (1-p)>c, where b and c denote, respectively, the benefit and cost of cooperation, while p is the error rate. This relation can be reformulated as an error threshold: cooperation can only emerge if the probability of making a mistake is below a critical value. We note, however, that cooperation in the continuous Prisoner's Dilemma with noise does not seem to be evolutionarily stable: while it is possible to find cooperative strategies that resist invasion by defectors, such cooperators are generally invaded by more cooperative strategies which eventually yield to defectors. Thus, the long-term evolution of the continuous Prisoner's Dilemma is either characterized by unending cycles or by stable polymorphisms of cooperators and defectors.

Biological Evolution↗
PubMed2001

An examination of polymorphic genes and folate metabolism in mothers affected by a spina bifida pregnancy.

The effect of four polymorphic genes of folate-dependent methionine biosynthesis have been investigated in mothers affected by a neural tube defect pregnancy (NTD) and matched controls. The influence of the various genotypes on total red cell 5-methyl-H(4)folate,5,10-methenyl-H(4)folate, and 5-formyl-H(4)folate is reported, as is the effect on homocysteine and radioassay folate in both serum and red cells. All of the single nucleotide polymorphisms studied would seem to contribute to the cellular folate profile in some way. From the data presented, and from the work of others, it is likely that C677T 5,10-methylenetetrahydrofolate reductase is the most important of these polymorphisms. Control mother folate profiles seem reasonably predictive of any given methionine cycle mutation, but profiles in NTD mothers do not. On this basis, it seems likely that some other, as yet unidentified folate lesion is causal for NTD. In NTD-C677T 5,10-methylenetetrahydrofolate reductase in particular, indexes of folate depletion such as high-performance liquid chromatography (HPLC) folate level, oligo-gamma-glutamyl chain length, homocysteine, and radioassay folate values all seem to deteriorate with increased mutant allele carriage. This indicates that this folate polymorphism may provide a critical threshold effect that helps to promote NTD occurrence in the presence of another, as yet unidentified folate-related factor. In more general terms, on a by genotype basis, all 11 genotypes studied give NTD mothers a higher homocysteine compared to controls. Furthermore, a trend that is less universal indicates that NTD mothers have higher 5,10-methenyl-H(4)folate and 5-methyl-H(4)folate levels and lower 5-formyl-H(4)folate and H(4)PteGlu(1) levels than do controls. One of the most consistent, and possibly specific, differences between participant groups is a statistically significant elevation of 5,10-methenyl-H(4)folate in NTD mothers (affects three genotypes). Possible interpretations of this finding are discussed.

Adult↗
PubMed1997

Intense exercise increases the post-exercise threshold for sweating.

We demonstrated previously that esophageal temperature (T(es)) remains elevated by approximately 0.5 degrees C for at least 65 min after intense exercise. Following exercise, average skin temperature (T(avg)) and skin blood flow returned rapidly to pre-exercise values even though T(es) remained elevated, indicating that the T(es) threshold for vasodilation is elevated during this period. The present study evaluates the hypothesis that the threshold for sweating is also increased following intense exercise. Four males and three females were immersed in water (water temperature, T(w) = 42 degrees C) until onset of sweating (Immersion 1), followed by recovery in air (air temperature, T(a) = 24 degrees C). At a T(a) of 24 degrees C, 15 min of cycle ergometry (70% VO2max) (Exercise) was then followed by 30 min of recovery. Subjects were then immersed again (T(w) = 42 degrees C) until onset of sweating (Immersion 2). Baseline T(es) and T(skavg) were 37.0 (0.1) degrees C and 32.3 (0.3) degrees C, respectively. Because the T(skavg) at the onset of sweating was different during Exercise [30.9 (0.3) degrees C] than during Immersion 1 and Immersion 2 [36.8 (0.2) degrees C and 36.4 (0.2) degrees C, respectively] a corrected core temperature, T((es) (calculated)), was calculated at a single designated skin temperature, T((sk)(designated)), as follows: T((es)(calculated)) = T(es) + [beta/(1-beta)][T(skavg)-T((sk)(designated))]. The T((sk)(designated)) was set at 36.5 degrees C (mean of Immersion 1 and Immersion 2 conditions) and beta represents the fractional contribution of T(skavg) to the sweating response (beta for sweating = 0.1). While T((es)(calculated)) at the onset of sweating was significantly lower during exercise [36.7 (0.2) degrees C] than during Immersion 1 [37.1 (0.1) degrees C], the threshold of sweating during Immersion 2 [37.3 (0.1) degrees C] was greater than during both Exercise and Immersion 1 (P < 0.05). We conclude that intense exercise decreases the sweating threshold during exercise itself, but elicits a subsequent short-term increase in the resting sweating threshold.

Adult↗
PubMed1977

The relation between end-tidal CO2 and discharge patterns of sympathetic preganglionic neurons.

In 11 Nembutal-anesthetized, vagotomized, thoracotomized, paralyzed and artificially ventilated cats, the electrical activity of 32 single sympathetic preganglionic neurons (SPNs), dissected from the cervical nerve was recorded at various end-tidal CO2 levels, together with the activity of the phrenic nerve. Seven of these neurons were insensitive to CO2 changes, within a range of end-tidal CO2 values from 1;0 to 10;0%. All 7 had a background firing pattern without respiratory modulation, even at the highest CO2 levels tested, i.e., had the same firing frequency in both phases of the phrenic nerve activity cycle. Seventeen units were silent at low CO2 levels, began to discharge at particular CO2 levels (on the average, at 2.3% CO2) and increased their firing frequency (on the average, by 0.9 spikes/sec/% CO2) as end-tidal CO2 was raised above the threshold level. Their background discharge pattern was characterized by firing only in the inspiratory phase of the phrenic nerve activity cycle. Three units had firing which was CO2-independent within a range of low CO2 concentrations and which increased as CO2 concentration was increased above this range. These units fired throughout the phrenic nerve activity cycle but had their peak frequency in inspiration. Five units had a firing frequency which was highest at low CO2 and which decreased with increasing CO2 levels. These units had their peak frequency in expiration. These results show that the output of this SPN population is strongly influenced by CO2 within the range of concentrations tested. The finding that sensitivity to CO2 changes is a property only of SPNs with respiratory-modulated firing pattern suggests that the CO2-dependent input is relayed to these SPNs via the respiratory center; A comparison of data obtained under hypocapnic conditions with data obtained in previous studies in normocapnic cats with mid-cervical spinal cord transections suggests that brain stem inspiratory neurons represent a major excitatory input to this SPN pool.

Action Potentials↗
PubMed1996

Allometry and simple epidemic models for microparasites.

Simple mathematical models for microparasites offer a useful way to examine the population dynamics of different viral and bacterial pathogens. One constraint in applying these models in free-living host populations is the paucity of data with which to estimate transmission rates. Here we recast a standard epidemiological model by setting the birth and death rates of the host population and its density as simple allometric functions of host body weight. We then use standard threshold theorems for the model in order to estimate the minimum rate of transmission for the parasite to establish itself in a mammalian host population. Transmission rates that produce different comparable values of the parasites' basic reproductive number, RO, are themselves allometric functions of host body size. We have extended the model to show that hosts having different body sizes suffer epidemic outbreaks whose frequency scales with body size. The expected epidemic periods for pathogens in different mammalian populations correspond to cycles observed in free-living populations.

Animals↗
PubMed2002

A spatially continuous mean field theory of electrocortical activity.

A set of nonlinear continuum field equations is presented which describes the dynamics of neural activity in cortex. These take into account the most pertinent anatomical and physiological features found in cortex with all parameter values obtainable from independent experiment. Derivation of a white noise fluctuation spectrum from a linearized set of equations shows the presence of strong resonances that correspond to electroencephalographically observed 0.3-4 Hz (mammalian delta), 4-8 Hz (mammalian theta), 8-13 Hz (mammalian alpha) and >13 Hz (mammalian beta) activity. Numerical solutions of a full set of one-dimensional nonlinear equations include properties analogous to cortical evoked potentials, travelling waves at experimentally observed velocities, threshold type spike activity and limit cycle, chaotic and noise driven oscillations at the frequency of the mammalian alpha rhythm. All these types of behaviour are generated with parameters that are within ranges reported experimentally. The strong dependence of the phenomena observed on inhibitory-inhibitory interactions is demonstrated. These results suggest that the classically described alpha may be instantiated in a number of qualitatively distinct dynamical regimes, all of which depend on the integrity of inhibitory-inhibitory population interactions.

Algorithms↗
PubMed1997

Hypertonic saline does not reverse the sodium channel blocking actions of lidocaine: evidence from electrophysiologic and defibrillation studies.

Studies have shown that increasing extracellular sodium concentration can partially reverse sodium channel blockade. However, there is conflicting in vitro evidence in this regard for lidocaine. The effects of lidocaine on cardiac electrophysiology and defibrillation were studied in a basal and hypernatremic state to determine reversibility of sodium channel blockade. Electrophysiologic studies measured right ventricular effective refractory period at 350 ms pacing cycle length and QRS interval, JT interval, and monophasic action potential duration during sinus rhythm and right ventricular pacing (350 ms cycle length) in 14 pentobarbital-anesthetized swine (25-30 kg). Defibrillation threshold (DFT) was measured by quantitating successful conversion of sustained ventricular fibrillation to normal sinus rhythm. Each pig was randomly assigned to a treatment group with three study phases; group 1 = baseline, lidocaine (20 mg/kg/h), and lidocaine plus placebo (D5W; n = 7); and group 2 = baseline, lidocaine, and lidocaine plus hypertonic saline (2-3 mM/kg/h; n = 7). In groups 1 and 2, lidocaine infused alone significantly (p < 0.01) increased DFT values from baseline (9.8 +/- 3.9 to 15.7 +/- 5.8 J and 8.9 +/- 2.9 to 14.7 +/- 5.4 J, respectively) and increased QRS duration from baseline during right ventricular pacing (89 +/- 6 to 109 +/- 10 ms; p < 0.01; and 87 +/- 6 to 103 +/- 12 ms; p < 0.01). Lidocaine alone reduced right ventricular action potential duration (APD) in groups 1 and 2 (214 +/- 18 to 206 +/- 20 ms; p < 0.10; and 228 +/- 8 to 212 +/- 8 ms; p < 0.05), respectively, and it reduced paced JT interval in both groups (194 +/- 20 to 184 +/- 18 ms; p < 0.10; and 200 +/- 12 to 183 +/- 16 ms; p < 0.05), respectively. When hypertonic saline was added to lidocaine, DFT and QRS duration values were unaffected (14.7 +/- 5.4 to 16.1 +/- 3.7 J and 103 +/- 12 to 100 +/- 11 ms, respectively). However, APD and JT intervals returned to basal values when hypertonic saline was added to lidocaine (212 +/- 8 to 225 +/- 13; p < 0.05; and 183 +/- 16 to 192 +/- 18; p < 0.05, respectively). When D5W was added in the control group, no changes occurred in DFT or electrophysiologic values. Lidocaine slowed ventricular conduction velocity and reduced APD. The administration of hypertonic saline to increase extracellular sodium concentrations failed to reverse the effect of lidocaine on conduction-velocity slowing or elevated DFT values. Hypertonic saline did reverse the effects of lidocaine on repolarization parameters. These data suggest that shortening of repolarization is not a mechanism by which lidocaine makes it more difficult to defibrillate the heart.

Action Potentials↗
PubMed2000

Activated mitogenic signaling induces a process of dedifferentiation in Alzheimer's disease that eventually results in cell death.

Neurodegeneration in Alzheimer's disease (AD) is associated with the appearance of dystrophic neuronal growth profiles that most likely reflect an impairment of neuronal reorganization. This process of morphodysregulation, which eventually goes awry and becomes a disease itself, might be triggered either by a variety of life events that place an additional burden on the plastic capability of the brain or by genetic pertubations that shift the threshold for decompensation. This paper summarizes recent evidence that impairment of the p21ras intracellular signal transduction, which is is mediated by a hierarchy of phosphorylation signals and eventually results in loss of differentiation control and an attempt of neurons to re-enter the cell-cycle, is critically involved in this process. Neurodegeneration might thus be viewed as an alternative effector pathway of those events that in the dividing cell would lead to cellular transformation. This hypothesis might be of heuristic value for the development of a therapeutic strategy.

Alzheimer Disease↗
PubMedDate not supplied

Changes in ventricular fibrillation threshold during repeated short-term coronary occlusion and release.

The time course of changes in VFT was determined during the 1st phase of arrhythmia following coronary occlusion and during consecutive reperfusion in five repeated periods of occlusion and reperfusion in 10 mongrel dogs (17--24 kg). VFT was determined using a square wave pulse series of 140 ms duration which was triggered by the R-wave of the ECG and placed into the vulnerable period of the cardiac cycle. After acute occlusion VFT decreased to a minimum level within a few minutes and then increased again slowly up to the control value which was reached about 20 min after the ligation. When the occlusions were repeated several times the extent of the decrease in VFT became increasingly less and its duration increasingly shorter until finally there was no significant decrease in VFT. Reperfusion after coronary occlusion led to an abrupt decrease in VFT within 1 min, followed by a rapid increase to the control value. This time course did not depend upon the number of prior occlusions. The results show that in the case of repeating short-term coronary occlusions one cannot expect comparable VFT time courses for the consecutive periods of occlusion except for the 1st and 2nd ones. Differing mechanisms leading to the occurrence of VF after coronary ligation and during reperfusion are discussed.

Animals↗
PubMed2002

Physiological variables at lactate threshold under-represent cycling time-trial intensity.

BACKGROUND: The importance of lactate threshold (LT) as a determinant of performance in endurance sports has been established. In addition, it has been shown that during running and selected other endurance competitions, athletes perform at a velocity and VO2 slightly above LT for the duration of the event. Prior work indicates however, that this may not be true during a cycling time-trial (TT). This investigation sought to compare physiological variables during a 20-k TT with those corresponding to the athlete's LT. METHODS: Thirteen male cyclists (22.7+/-0.8 yrs; 180.6+/-8.0 cm; 77.1+/-10.0 kg; 8.3+/-2.5% fat; 4.9+/-2.2 l x min(-1), VO2max) participated in the study. Subjects performed a graded protocol starting at 150 Watts (W) to determine LT (2 mmol x L(-1) above baseline) which consisted of 20 W increases every 4-min. Following an 8 min-recovery, subjects cycled at the wattage corresponding to LT-20 W for 1 min and then workload increased 20 W every minute until volitional exhaustion to determine VO2max x On a separate occasion a self-paced, 20-k TT was completed. RESULTS: Mean values of blood lactate, HR and % HRmax, VO2 and % VO2max, and power output throughout the 20-k TT were greater (p<0.01) than those at LT. During the TT these cyclists performed at an intensity well above LT (blood lactate=252.0+/-0.1%, HR=9.4+/-0.03%, %HRmax=9.2+/-0.15%, VO2=26.5+/-0.7%, %VO2max=17.2+/-0.08% and power out-put=14.8+/-0.14% above LT) for over 30 min. CONCLUSIONS: Therefore, while LT may be highly correlated to performance, it may not be representative of race pace for a cycling TT, and may be questionable as a benchmark used to prescribe training intensity for competitive TT-cycling.

Adult↗
PubMed2005

Relationship between breath-hold time and physical performance in patients with cystic fibrosis.

Rehabilitation including physiotherapy is an important part of the treatment used to help improve the quality of life of patients with cystic fibrosis (CF). The aim of this study was to determine the value of the breath-hold time as an index of exercise tolerance in patients with CF. Eighteen patients in different states of CF were included. The breath-hold time was measured in all patients. The fitness level was assessed by means of a progressive exercise test on a cycle-ergometer. During the test, oxygen uptake (VO(2)) and carbon dioxide elimination (VCO(2)) were measured breath by breath. The VO(2) and working capacity (WC) were computed at the anaerobic threshold (AT) and at peak. Duration of breath-hold was 24.7 +/- 2.87 (mean +/- SEM) seconds, varying between 10 and 58. The breath-hold time (BHT) displayed a significant correlation with VO(2) (r = 0.898), WC (r = 0.899) at the AT, and the peak VO(2) (r = 0.895). Regression equations were: VO(2) at the AT (ml/kg) = 5.53 + 0.42 x BHT and WC at the AT (watt/kg) = 0.56 + 0.38 x BHT Our results suggest that the voluntary breath-hold time might be a useful index for prediction of the exercise tolerance of CF patients.

Adolescent↗
PubMed2002

Muscle deoxygenation as related to work rate.

PURPOSE: The kinetics of the decrease in venous O(2) content in response to constant work rate exercise below the lactic acidosis threshold (LAT) is very rapid, reaching a constant value by approximately 1 min. However, for work rates above the LAT, a slow further decrease in venous O(2) content takes place that is attributable to the Bohr effect rather than further decrease in end capillary PO. We hypothesized that similar differences, with respect to the LAT, will be observed in muscle deoxygenation kinetics when studied with near-infrared spectroscopy (NIRS). METHODS: Twelve normal subjects performed three constant work rate tests from unloaded cycling at 60% of LAT, 80% LAT, each with four repetitions, and above LAT (LAT + 35% between LAT and VO(2max) three times, on a cycle ergometer for 6 min. We measured tissue deoxygenation with NIRS, with the probe over the vastus lateralis muscle, time-averaging the repetitions. Gas exchange and heart rate (HR) were measured breath-by-breath and beat-by-beat. RESULTS: Tissue deoxygenation kinetics were significantly faster than VO(2) and HR at 60%- and 80%-LAT work rates. By 1 min of exercise, deoxygenation was constant for the work rate below the LAT. At 30 s, tissue deoxygenation was 70-95% complete, whereas VO(2) and HR were only 30-60% complete. For the work rate above the LAT, a steady state for muscle deoxygenation was not reached during the 6 min of exercise. After 1 min of above-LAT exercise, either one of two patterns of slow change in tissue oxygenation developed, deoxygenation or reoxygenation. It is postulated that these different responses might be due to effects of the exercise lactic acidosis. H accompanying lactate increase might cause further deoxygenation due to the Bohr effect, and acidosis-induced vasodilatation might cause reoxygenation after the initial deoxygenation. CONCLUSION: 1) The kinetics of tissue deoxygenation are significantly more rapid than VO(2) and HR kinetics at all work rates studied, and 2) steady-state in tissue deoxygenation is seen by 1 min of constant work rate exercise below the LAT, but this is much delayed for work rates above the LAT.

Acidosis, Lactic↗
PubMed1999

Kinetics of oxygen uptake during supine and upright heavy exercise.

It is presently unclear how the fast and slow components of pulmonary oxygen uptake (VO(2)) kinetics would be altered by body posture during heavy exercise [i.e., above the lactate threshold (LT)]. Nine subjects performed transitions from unloaded cycling to work rates representing moderate (below the estimated LT) and heavy exercise (VO(2) equal to 50% of the difference between LT and peak VO(2)) under conditions of upright and supine positions. During moderate exercise, the steady-state increase in VO(2) was similar in the two positions, but VO(2) kinetics were slower in the supine position. During heavy exercise, the rate of adjustment of VO(2) to the 6-min value was also slower in the supine position but was characterized by a significant reduction in the amplitude of the fast component of VO(2), without a significant slowing of the phase 2 time constant. However, the amplitude of the slow component was significantly increased, such that the end-exercise VO(2) was the same in the two positions. The changes in VO(2) kinetics for the supine vs. upright position were paralleled by a blunted response of heart rate at 2 min into exercise during supine compared with upright heavy exercise. Thus the supine position was associated with not only a greater amplitude of the slow component for VO(2) but also, concomitantly, with a reduced amplitude of the fast component; this latter effect may be due, at least in part, to an attenuated early rise in heart rate in the supine position.

Adult↗
PubMed1991

Effect of long-term enalapril therapy on cardiopulmonary exercise performance in men with mild heart failure and previous myocardial infarction.

Forty-one men with documented myocardial infarction greater than 6 months previously were randomized to long-term (48 weeks) therapy with placebo or enalapril on a double-blind basis. All patients were receiving concurrent therapy with digitalis and a diuretic drug for symptomatic heart failure (functional class II or III). The mean age was 64 +/- 7.3 years and no patient suffered from exertional chest pain. Patients underwent maximal cardiopulmonary exertional chest pain. Patients underwent maximal cardiopulmonary exercise testing to exhaustion on an ergometer cycle nine times over the course of 48 weeks. Gas exchange data were collected on a breath by breath basis with use of a continuous ramp protocol. In the placebo group (n = 21), the mean (+/- SD) peak oxygen consumption (VO2) at baseline was 18.8 +/- 5.2 versus 18.5 +/- 5.5 ml/kg per min at 48 weeks (-1.4%, p = NS). In the enalapril group (n = 20), the corresponding values were 18.1 +/- 3.1 versus 18.3 +/- 2.6 ml/kg per min (+2.8%, p = NS). The mean VO2 at the anaerobic threshold for the placebo group at baseline study was 13.1 +/- 3.5 versus 12.8 +/- 2.1 ml/kg per min at 48 weeks (-2.2%, p = NS). The corresponding values for the enalapril group were 11.8 +/- 2.3 versus 11.8 +/- 2.4 ml/kg per min (+1.4%, p = NS). The mean total exercise duration in the placebo group at baseline study was 589 +/- 153 versus 620 +/- 181 s at 48 weeks (+5.4%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold↗
PubMed1996

Effect of hypoglycemia on thermoregulatory responses.

The effects of hypoglycemia on sweating, skin blood perfusion, and shivering responses were investigated in 10 healthy male volunteers. They exercised on an underwater cycle ergometer while immersed to the neck in 28 degrees C water for 20 min at 50% of their maximal work rate. The exercise-induced elevation in esophageal temperature (T(es)) initiated the sweating response (Esw) and increased skin blood perfusion (SkBP) as measured at the forehead. In the 99-min postexercise immersion period, the values of T es relative to resting level (delta T(es)) at which Esw abated, SkBP reached preexercise values, and shivering commenced were defined as the delta T(es) thresholds for cessation of sweating, passive vasodilation, and onset of shivering, respectively. Two trials were conducted 1 wk apart. The subject was hypoglycemic in one trial and euglycemic in the other (plasma glucose was maintained at 2.8 and 5 mM, respectively) with the use of the hyperinsulinemic (insulin infusion rate = 60 mU.m-2.min-1) glucose-clamp technique. Oxygen uptake, Esw, T(es), mean skin temperature, heat flux from the skin, and SkBP were recorded at minute intervals. Although heat flux and SkBP attained significantly higher end-exercise levels during euglycemia, the responses were similar during the postexercise cooling period. Hypoglycemia did not affect the Esw response during the exercise and cooling periods. Whereas the exercise delta T(es) response was unaffected by hypoglycemia, the decrease in T(es) was greater (P < or = 0.005) during the hypoglycemic than during the euglycemic condition. Hypoglycemia did not alter the delta T(es) threshold for cessation of sweating and passive vasodilation but reduced (P < or = 0.001) the delta T(es) threshold for onset of shivering (from -0.09 +/- 0.07 degrees C in the euglycemic condition to -0.65 +/- 0.12 degrees C in the hypoglycemic condition). The present results indicate that hypoglycemia (2.8 mM) does not affect the delta T(es) threshold for cessation of thermoregulatory sweating or the threshold for passive vasodilation during recovery from exercise-induced moderate heat stress but that it decreases the core temperature threshold for shivering during cold exposure.

Adult↗
PubMed1986

Intracellular pH controls growth factor-induced ribosomal protein S6 phosphorylation and protein synthesis in the G0----G1 transition of fibroblasts.

Mitogen-induced intracellular alkalinization mediated by activation of a Na+/H+ antiporter is a common feature of eukaryotic cells stimulated to divide. A Chinese hamster fibroblast mutant (PS120) lacking Na+/H+ antiport activity (Pouysségur et al., Proc natl acad sci US 81 (1984) 4833) [42] possesses an intracellular pH (pHi) 0.2-0.3 units lower than the wild type (CCL39) and requires a more alkaline pHout (pHo) for growth. Here, we show that serum-stimulated ribosomal protein S6 phosphorylation, protein synthesis activation and DNA synthesis re-initiation are pH-regulated events that display a similar threshold pHo value (6.60) in CCL39 cells. pH-Dependencies for initiation of all three events are shifted toward higher pHo values in the mutant PS120, indicating that growth factor-induced alkalinization has a permissive effect on the pleiotypic response. However, cytoplasmic alkalinization per se is insufficient to trigger S6 phosphorylation, polysome formation, and subsequent DNA synthesis. Transient exposure to a non-permissive pHo (6.5) inhibits both the rate of leucine incorporation into proteins and the progression through the G1 phase of the cell cycle. In contrast, cells committed to DNA synthesis are unaltered by the acidic pHo. These observations suggest that pHi by controlling the rate of protein synthesis play a determinant role in the control of cell division.

Amiloride↗