Effects of exercise and passive head-up tilt on fractal and complexity properties of heart rate dynamics

tk;1Passive head-up tilt and exercise result in specific changes in the spectral characteristics of heart rate (HR) variability as a result of reduced vagal and enhanced sympathetic outflow. Recently analytic methods based on nonlinear system theory have been developed to characterize the nonlinear features in HR dynamics. This study was designed to assess the changes in the fractal and complexity measures of HR behavior during the passive head-up tilt and during exercise. Fractal exponent (alpha(1)) and approximate entropy (ApEn), measures of short-term correlation properties and overall complexity of HR, respectively, along with spectral components of HR variability were analyzed during a passive head-up tilt test (n = 10) and a low-intensity steady-state exercise (n = 20) in healthy subjects. We observed that alpha(1) increased during the tilt test (from 0.85 +/- 0.22 to 1.48 +/- 0.20; P < 0.001) and during the exercise (from 1.00 +/- 0.22 to 1.37 +/- 0. 14; P < 0.001). ApEn also increased during the exercise (from 1.04 +/- 0.11 to 1. 11 +/- 0.08; P < 0.05), but it did not change during the tilt test. The normalized high-frequency spectral component decreased and the low-frequency component increased similarly during both the exercise and the tilt test (P < 0.001 for all). Exercise and passive tilt result in an increase of short-term fractal correlation properties of HR dynamics, which is related to changes in the balance between the low- and high-frequency oscillations in controlled situations. Overall complexity of HR dynamics increases during exercise but not during passive tilt.     

Contrasting effects of presynaptic alpha2-adrenergic autoinhibition and pharmacologic augmentation of presynaptic inhibition on sympathetic heart rate control

Presynaptic alpha2-adrenergic receptors are known to exert feedback inhibition on norepinephrine release from the sympathetic nerve terminals. To elucidate the dynamic characteristics of the inhibition, we stimulated the right cardiac sympathetic nerve according to a binary white noise signal while measuring heart rate (HR) in anesthetized rabbits (n = 6). We estimated the transfer function from cardiac sympathetic nerve stimulation to HR and the corresponding step response of HR, with and without the blockade of presynaptic inhibition by yohimbine (1 mg/kg followed by 0.1 mg.kg(-1).h(-1) iv). We also examined the effect of the alpha2-adrenergic receptor agonist clonidine (0.3 and 1.5 mg.kg(-1).h(-1) iv) in different rabbits (n = 5). Yohimbine increased the maximum step response (from 7.2 +/- 0.8 to 12.2 +/- 1.7 beats/min, means +/- SE, P < 0.05) without significantly affecting the initial slope (0.93 +/- 0.23 vs. 0.94 +/- 0.22 beats.min(-1).s(-1)). Higher dose but not lower dose clonidine significantly decreased the maximum step response (from 6.3 +/- 0.8 to 6.8 +/- 1.0 and 2.8 +/- 0.5 beats/min, P < 0.05) and also reduced the initial slope (from 0.56 +/- 0.07 to 0.51 +/- 0.04 and 0.22 +/- 0.06 beats.min(-1).s(-1), P < 0.05). Our findings indicate that presynaptic alpha2-adrenergic autoinhibition limits the maximum response without significantly compromising the rapidity of effector response. In contrast, pharmacologic augmentation of the presynaptic inhibition not only attenuates the maximum response but also results in a sluggish effector response.     

Heterogeneous limb vascular responsiveness to shear stimuli during dynamic exercise in humans.

Arm and leg vascular responsiveness to comparable shear stimuli during isolated dynamic exercise has not been assessed in humans. Consequently, six young cyclists performed incremental, intermittent handgrip exercise (arm) and knee-extensor exercise (leg) from 5 to 60% of maximal work rate (WR). Ultrasound Doppler measurements were taken in the brachial artery (BA), common femoral artery (CFA), and deep femoral artery (DFA) at rest and at each WR to assess diameter and sheer rate changes. Exercise at 60% maximum WR increased shear rate to the same degree in the CFA (314.3 +/- 33.3 s(-1)) and BA (303.3 +/- 26.3 s(-1)), but was significantly higher in the DFA (712.6 +/- 88.3 s(-1)). Compared with rest, exercise at 60% maximum WR did not alter CFA vessel diameter, but increased BA diameter (0.42 +/- 0.01 to 0.49 +/- 0.01 cm) and DFA diameter (0.59 +/- 0.05 to 0.64 +/- 0.04 cm). These data from the DFA demonstrate for the first time a substantial improvement in vascular reactivity in a conduit vessel only slightly distal to the CFA. However, despite comparable dilation between the BA and DFA, the slope of the relationship between vessel diameter and shear rate was much greater in the arm (2.4 x 10(-4) +/- 4.6 x 10(-5) cm/s) than in either the DFA (8.9 x 10(-5) +/- 1.5 x 10(-5) cm/s) or CFA (2.1 x 10(-5) +/- 1.1 x 10(-5) cm/s). Together, these findings reveal a substantial heterogeneity in vascular responsiveness in the leg during dynamic exercise but demonstrate that conduit vessel dilation for a given change in shear rate is, nonetheless, reduced in the leg compared with the arm.     

Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation.

Both a large heart rate (HR) increase at exercise onset and a slow heart rate (HR) recovery following the termination of exercise have been linked to an increased risk for ventricular fibrillation (VF) in patients with coronary artery disease. Endurance exercise training can alter cardiac autonomic regulation. Therefore, it is possible that this intervention could restore a more normal HR regulation in high-risk individuals. To test this hypothesis, HR and HR variability (HRV, 0.24- to 1.04-Hz frequency component; an index of cardiac vagal activity) responses to submaximal exercise were measured 30, 60, and 120 s after exercise onset and 30, 60, and 120 s following the termination of exercise in dogs with healed myocardial infarctions known to be susceptible (n = 19) to VF (induced by a 2-min coronary occlusion during the last minute of a submaximal exercise test). These studies were then repeated after either a 10-wk exercise program (treadmill running, n = 10) or an equivalent sedentary period (n = 9). After 10 wk, the response to exercise was not altered in the sedentary animals. In contrast, endurance exercise increased indexes of cardiac vagal activity such that HR at exercise onset was reduced (30 s after exercise onset: HR pretraining 179 +/- 8.4 vs. posttraining 151.4 +/- 6.6 beats/min; HRV pretraining 4.0 +/- 0.4 vs. posttraining 5.8 +/- 0.4 ln ms(2)), whereas HR recovery 30 s after the termination of exercise increased (HR pretraining 186 +/- 7.8 vs. posttraining 159.4 +/- 7.7 beats/min; HRV pretraining 2.4 +/- 0.3 vs. posttraining 4.0 +/- 0.6 ln ms(2)). Thus endurance exercise training restored a more normal HR regulation in dogs susceptible to VF.     

Effects of aerobic training on heart rate dynamics in sedentary subjects.

This study was designed to assess the effects of moderate- and high-volume aerobic training on the time domain and on spectral and fractal heart rate (HR) variability indexes. Sedentary subjects were randomized into groups with moderate-volume training (n = 20), high-volume training (n = 20), and controls (n = 15). The training period was 8 wk, including 6 sessions/wk at an intensity of 70-80% of the maximum HR, lasting for 30 min/session in the moderate-volume group and 60 min/session in the high-volume group. Time domain, frequency domain, and short-term fractal scaling measures of HR variability were analyzed over a 24-h period. Mean HR decreased from 70 +/- 7 to 64 +/- 8 beats/min and from 67 +/- 5 to 60 +/- 6 beats/min (P < 0.001 for both) for the moderate- and high-volume training groups, respectively. The normalized high-frequency spectral component increased in both groups (P < 0.05). The normalized low-frequency component decreased significantly (P < 0.05), resulting in a marked decrease in low frequency-to-high frequency ratio in both groups. In addition, short-term scaling exponent decreased in both groups (P < 0.001). There were no significant differences in the changes of HR variability indexes between groups. Aerobic training in sedentary subjects results in altered autonomic regulation of HR toward vagal dominance. A moderate training volume is a sufficient intervention to induce these beneficial effects.     

Unexpected course of nonlinear cardiac interbeat interval dynamics during childhood and adolescence

The fluctuations of the cardiac interbeat series contain rich information because they reflect variations of other functions on different time scales (e.g., respiration or blood pressure control). Nonlinear measures such as complexity and fractal scaling properties derived from 24 h heart rate dynamics of healthy subjects vary from childhood to old age. In this study, the age-related variations during childhood and adolescence were addressed. In particular, the cardiac interbeat interval series was quantified with respect to complexity and fractal scaling properties. The R-R interval series of 409 healthy children and adolescents (age range: 1 to 22 years, 220 females) was analyzed with respect to complexity (Approximate Entropy, ApEn) and fractal scaling properties on three time scales: long-term (slope β of the power spectrum, log power vs. log frequency, in the frequency range 10(-4) to 10(-2) Hz) intermediate-term (DFA, detrended fluctuation analysis, α(2)) and short-term (DFA α(1)). Unexpectedly, during age 7 to 13 years β and ApEn were higher compared to the age <7 years and age >13 years (β: -1.06 vs. -1.21; ApEn: 0.88 vs. 0.74). Hence, the heart rate dynamics were closer to a 1/f power law and most complex between 7 and 13 years. However, DFA α(1) and α(2) increased with progressing age similar to measures reflecting linear properties. In conclusion, the course of long-term fractal scaling properties and complexity of heart rate dynamics during childhood and adolescence indicates that these measures reflect complex changes possibly linked to hormonal changes during pre-puberty and puberty.     

Progesterone levels and litter performance of sows following postpartum administration of prostaglandin F(2alpha)

A total of 101 sows was used to examine postpartum progesterone levels and litter performance following administration of 15 mg prostaglandins F(2alpha) (PGF(2alpha) n = 48) given within 12 h after farrowing. Daily blood samples and rectal temperatures were taken from all sows during the first 3 d post partum. Plasma progesterone (P(4)) concentrations were determined by radioimmunoassay (RIA). Regardless of treatment, plasma P(4) levels for all sows decreased in a similar fashion over the 3 d sampled. Mean (+/- SEM) P(4) on Day 2 (0.55 +/- 0.06 ng/ml) and Day 3 (0.38 +/- 0.04 ng/ml) were lower (P<0.01) than on Day 1 (0.98 +/- 0.08 ng/ml). Rectal temperature did not differ between PGF(2alpha) treated and nontreated sows nor was it different over the days measured. Litter characteristics, including survival rates on Day 7 and at weaning, and body weight on Days 3 and 35, were not affected by treatment. It was concluded that PGF(2alpha) administration to sows within 12 h post farrowing had no affect on the rate of luteal regression, as determined by P(4) concentration, nor on subsequent litter performance.     

The dynamics of EEG entropy

The scaling properties of human EEG have so far been analyzed predominantly in the framework of detrended fluctuation analysis (DFA). In particular, these studies suggested the existence of power-law correlations in EEG. In DFA, EEG time series are tacitly assumed to be made up of fluctuations, whose scaling behavior reflects neurophysiologically important information and polynomial trends. Even though these trends are physiologically irrelevant, they must be eliminated (detrended) to reliably estimate such measures as Hurst exponent or fractal dimension. Here, we employ the diffusion entropy method to study the scaling behavior of EEG. Unlike DFA, this method does not rely on the assumption of trends superposed on EEG fluctuations. We find that the growth of diffusion entropy of EEG increments of awake subjects with closed eyes is arrested only after approximately 0.5 s. We demonstrate that the salient features of diffusion entropy dynamics of EEG, such as the existence of short-term scaling, asymptotic saturation, and alpha wave modulation, may be faithfully reproduced using a dissipative, first-order, stochastic differential equation—an extension of the Langevin equation. The structure of such a model is utterly different from the “noise+trend” paradigm of DFA. Consequently, we argue that the existence of scaling properties for EEG dynamics is an open question that necessitates further studies.     

Muscarinic potassium channels augment dynamic and static heart rate responses to vagal stimulation

Vagal control of heart rate (HR) is mediated by direct and indirect actions of ACh. Direct action of ACh activates the muscarinic K(+) (K(ACh)) channels, whereas indirect action inhibits adenylyl cyclase. The role of the K(ACh) channels in the overall picture of vagal HR control remains to be elucidated. We examined the role of the K(ACh) channels in the transfer characteristics of the HR response to vagal stimulation. In nine anesthetized sinoaortic-denerved and vagotomized rabbits, the vagal nerve was stimulated with a binary white-noise signal (0-10 Hz) for examination of the dynamic characteristic and in a step-wise manner (5, 10, 15, and 20 Hz/min) for examination of the static characteristic. The dynamic transfer function from vagal stimulation to HR approximated a first-order, low-pass filter with a lag time. Tertiapin, a selective K(ACh) channel blocker (30 nmol/kg iv), significantly decreased the dynamic gain from 5.0 +/- 1.2 to 2.0 +/- 0.6 (mean +/- SD) beats.min(-1).Hz(-1) (P < 0.01) and the corner frequency from 0.25 +/- 0.03 to 0.06 +/- 0.01 Hz (P < 0.01) without changing the lag time (0.37 +/- 0.04 vs. 0.39 +/- 0.05 s). Moreover, tertiapin significantly attenuated the vagal stimulation-induced HR decrease by 46 +/- 21, 58 +/- 18, 65 +/- 15, and 68 +/- 11% at stimulus frequencies of 5, 10, 15, and 20 Hz, respectively. We conclude that K(ACh) channels contribute to a rapid HR change and to a larger decrease in the steady-state HR in response to more potent tonic vagal stimulation.     

Solution structure and dynamics of cartilage aggrecan

We studied the structure and dynamics of porcine laryngeal aggrecan in solution using a range of noninvasive techniques: dynamic light scattering (DLS), small-angle neutron scattering (SANS), video particle tracking (VPT) microrheology, and diffusing wave spectroscopy (DWS). The data are analyzed within the framework of a combined static and dynamic scaling model, and evidence is found for reptation of the comb backbones with unentangled side-chain dynamics. Small-angle neutron scattering indicated standard polyelectrolyte scaling of the mesh size (xi) with concentration (c) in semidilute solutions for the whole aggrecan aggregate, xi = Ac(-0.47+/-0.04), with the prefactor (A) implying there is on average 60 nm between the aggrecan subunits along the backbone. VPT demonstrated large exponents for the power law dependence of the intrinsic viscosity (eta) on the polymer concentration in the semidilute concentration regime, eta approximately c(alpha); with alpha equal to 2.04 +/- 0.06 and 1.95 +/- 0.08 for the assembled and disassembled aggrecan aggregates, respectively. DWS at high frequencies (10(4)-10(5) Hz) gave evidence for internal Rouse modes of the aggrecan monomers, independent of the degree of self-assembly of the molecules.     

Influence of physical training on heart rate variability and baroreflex circulatory control

Nineteen males (aged 45-68 yr) were studied before and after either a period of regular endurance exercise [walk/jog 3-4 days/wk for 30 +/- 1 (SE) wk, n = 11] or unchanged physical activity (38 +/- 2 wk, n = 8) (controls) to determine the influence of physical training on cardiac parasympathetic (vagal) tone and baroreflex control of heart rate (HR) and limb vascular resistance (VR) at rest in middle-aged and older men. Training resulted in a marked increase in maximal O2 uptake (31.6 +/- 1.2 vs. 41.0 +/- 1.8 ml.kg-1.min-1, 2.56 +/- 0.16 vs. 3.20 +/- 0.18 l/min, P less than 0.05) and small (P less than 0.05) reductions in body weight (81.2 +/- 3.5 vs. 78.7 +/- 4.0 kg) and body fat (23.8 +/- 1.3 vs. 20.9 +/- 1.3%). HR at rest was slightly, but consistently, lower after training (63 +/- 2 vs. 58 +/- 1 beats/min, P less than 0.05). In general, HR variability (index of cardiac vagal tone) was greater after training. Chronotropic responsiveness to either brief carotid baroreflex stimulation (neck suction) or inhibition (neck pressure), or to non-specific arterial baroreflex inhibition induced by a hypotensive level of lower body suction, was unchanged after training. In contrast, the magnitude of the reflex increase in forearm VR in response to three levels of lower body suction was markedly attenuated after training (38-59%; P less than 0.05 at -10 and -30 mmHg; P = 0.07 at -20 mmHg). None of these variables or responses was altered over time in the controls. These findings indicate that in healthy, previously sedentary, middle-aged and older men, strenuous and prolonged endurance training 1) elicits large increases in maximal exercise capacity and small reductions in HR at rest, 2) may increase cardiac vagal tone at rest, 3) does not alter arterial baroreflex control of HR, and 4) results in a diminished forearm vasoconstrictor response to reductions in baroreflex sympathoinhibition.     

Neuromuscular plasticity during and following 3 wk of human forearm cast immobilization

Prolonged reductions in muscle activity results in alterations in neuromuscular properties; however, the time course of adaptations is not fully understood, and many of the specific adaptations have not been identified. This study evaluated the temporal evolution of adaptations in neuromuscular properties during and following 3 wk of immobilization. We utilized a combination of techniques involving nerve stimulation and transcranial magnetic stimulation to assess changes in central activation of muscle, along with spinal (H reflex) and corticospinal excitability [i.e., motor-evoked potential (MEP) amplitude, silent period (SP)] and contractile properties in 10 healthy humans undergoing 3 wk of forearm immobilization and 9 control subjects. Immobilization induced deficits in central activation (85 +/- 3 to 67 +/- 7% ) that returned to baseline levels 1 wk after cast removal. The flexor carpii radialis MEP amplitude increased greater than twofold after the first week of immobilization and remained elevated throughout immobilization and 1 wk after cast removal. Additionally, we observed a prolongation of the SP 1 wk after cast removal compared with baseline (78.5 +/- 7.1 to 98.2 +/- 8.7 ms). The contractile properties were also altered, since the rate of evoked force relaxation was slower following immobilization (-14.5 +/- 1.4 to -11.3 +/- 1.0% peak force/ms), and remained depressed 1 wk after cast removal (-10.5 +/- 0.8% peak force/ms). These observations detail the time course of adaptations in corticospinal and contractile properties associated with disuse and illustrate the profound effect of immobilization on the human neuromuscular system as evidenced by the alterations in corticospinal excitability persisting 1 wk following cast removal.     

Gadolinium prevents stretch-mediated contractile dysfunction in isolated papillary muscles

We tested the hypothesis that overstretching the myocardium could induce and/or exacerbate contractile dysfunction via stretch-activated (SA) ion channels. Maximum developed tension (T(max)), normalized to a control value, was compared in guinea pig papillary muscles held at one of three resting lengths (physiological stretch, overstretch, and unloaded) for 85 min. Overstretched muscles exhibited decreased contractile force (T(max) = 0.77 +/- 0.03) compared with physiological and unloaded muscles (T(max) = 0.93 +/- 0.05 and 1.03 +/- 0.07, respectively). Gd(3+), an SA channel antagonist, eliminated the adverse effect of overstretching (T(max) = 0.98 +/- 0.06), but nifedipine, a dihydropyridine (DHP) antagonist of L-type calcium channels, did not (T(max) = 0.82 +/- 0.04). Exposure to modified hypoxia-reoxygenation (MHR) during physiological stretch resulted in decreased contractility (T(max) = 0.63 +/- 0.07), an effect that was exacerbated by overstretching (T(max) = 0.44 +/- 0.04). Gd(3+) mitigated the effects of overstretch during MHR (T(max) = 0.64 +/- 0.05), but DHP did not (T(max) = 0.48 +/- 0.04). These data suggest that overstretching of the myocardium contributes to contractile abnormalities via SA channels that are distinct from L-type calcium channels.     

Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis.

Juveniles of many species, including humans, display greater airway responsiveness than do adults. This may involve changes in airway smooth muscle function. In the present work we studied force production and shortening velocity in trachealis from 1-wk-old (1 wk), 3-wk-old (3 wk), and 3-mo-old (adult) guinea pigs. Strips were electrically stimulated (60 Hz, 18 V) at their optimal length (l(o)) to obtain maximum active stress (P(o)) and rate of stress generation. Then, force-velocity curves were elicited at 2.5 s from the onset of the stimulus. By applying a recently developed modification of Hill's equation for airway smooth muscle, the maximum shortening velocity at zero load (V(o)) and the value alpha. gamma/beta, an index of internal resistance to shortening (Rsi), were calculated (alpha, beta, and gamma are the constants of the equation). P(o) increased little with maturation, whereas the rate of stress generation increased significantly (0.40 +/- 0.03, 0.45 +/- 0.03, 0. 51 +/- 0.03 P(o)/s for 1 wk, 3 wk, and adult animals). V(o) slightly increased early with maturation to decrease significantly later (1. 79 +/- 0.67, 2.45 +/- 0.92, and 0.55 +/- 0.09 l(o)/s for 1 wk, 3 wk, and adult animals), whereas the Rsi showed an opposite trend (14.98 +/- 5.19, 8.99 +/- 3.01, and 32.07 +/- 5.54 mN. mm(-2). l(o)(-1). s for 1 wk, 3 wk, and adult animals). This early increase of force generation in combination with late increase of Rsi may explain the changes of V(o) with age. An elevated V(o) may contribute to the incidence of airway hyperresponsiveness in healthy juveniles.     

Transmural cardiac strains in the lateral wall of the ovine left ventricle

The constant-volume property of contracting cardiac muscle has been invoked in models of heart wall mechanics that predict that systolic subendocardial left ventricular (LV) wall thickening must significantly exceed subepicardial thickening. To examine this prediction, we implanted arrays of radiopaque markers to measure lateral equatorial wall transmural strains and global and regional LV geometry in seven sheep and studied the four-dimensional dynamics of these arrays using biplane videofluoroscopy (60 Hz) in anesthetized intact animals 1 and 8 wk after surgery. A transmural gradient of systolic lateral wall thickening was observed at 1 wk (P = 0.009; linear regression) but was no longer present at 8 wk (P = 0.243). Referenced to end diastole, group mean (+/-SD) end-systolic radial subepicardial, midwall, and subendocardial wall thickening strains were, respectively, 0.08 +/- 0.08, 0.14 +/- 0.08, and 0.22 +/- 0.12 at 1 wk and 0.19 +/- 0.07 (P = 0.02; 1 vs. 8 wk), 0.20 +/- 0.04, and 0.23 +/- 0.07 at 8 wk. With the exception of an 8-ml (7%) increase in end-diastolic volume (P = 0.04) from 1 to 8 wk, LV shape and hemodynamics were otherwise unchanged. We conclude that equivalent hemodynamics can be generated by the left ventricle with or without a transmural gradient of systolic wall thickening in this region; thus such a gradient is unlikely to be a fundamental property of the contracting LV myocardium. We discuss some implications of these findings regarding mechanisms involved in systolic wall thickening.     

Kinetic isotope effect studies on aspartate aminotransferase: evidence for a concerted 1,3 prototropic shift mechanism for the cytoplasmic isozyme and L-aspartate and dichotomy in mechanism

The C alpha primary hydrogen kinetic isotope effects (C alpha-KIEs) for the reaction of the cytoplasmic isozyme of aspartate aminotransferase (cAATase) with [alpha-2H]-L-aspartate are small and only slightly affected by deuterium oxide solvent (DV = 1.43 +/- 0.03 and DV/KAsp = 1.36 +/- 0.04 in H2O; DV = 1.44 +/- 0.01 and DV/KAsp = 1.61 +/- 0.06 in D2O). The D2O solvent KIEs (SKIEs) are somewhat larger and are essentially independent of deuterium at C alpha (D2OV = 2.21 +/- 0.07 and D2OV/KAsp = 1.70 +/- 0.03 with [alpha-1H]-L-aspartate; D2OV = 2.34 +/- 0.12 and D2OV/KAsp = 1.82 +/- 0.06 with [alpha-2H]-L- aspartate). The C alpha-KIEs on V and on V/KAsp are independent of pH from pH 5.0 to pH 10.0. These results support a rate-determining concerted 1,3 prototropic shift mechanism by the multiple KIE criteria [Hermes, J. D., Roeske, C. A., O'Leary, M. H., & Cleland, W. W. (1982) Biochemistry 21, 5106]. The large C alpha-KIEs for the reaction of mitochondrial AATase (mAATase) with L-glutamate (DV = 1.88 +/- 0.13 and DV/KGlu = 3.80 +/- 0.43 in H2O; DV = 1.57 +/- 0.05 and DV/KGlu = 4.21 +/- 0.19 in D2O) coupled with the relatively small SKIEs (D2OV = 1.58 +/- 0.04 and D2OV/KGlu = 1.25 +/- 0.05 with [alpha-1H]-L-glutamate; D2OV = 1.46 +/- 0.06 and D2OV/KGlu = 1.16 +/- 0.05 with [alpha-2H]-L-glutamate) are most consistent with a two-step mechanism for the 1,3 prototropic shift for this isozyme-substrate pair.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-range negative correlation of glucose dynamics in humans and its breakdown in diabetes mellitus

Diurnal fluctuations in glucose levels continuously monitored during normal daily life are investigated using an extended random walk analysis, referred to as detrended fluctuation analysis (DFA), in 12 nondiabetic subjects and 15 diabetic patients. The DFA exponent alpha = 1.25 +/- 0.29 for healthy individuals in the "long-range" (>2 h) regime is shown to be significantly (P < 0.01) smaller than the reference "uncorrelated" value of alpha = 1.5, suggesting that the instantaneous net effects of the dynamical balance of glucose flux and reflux, causing temporal changes in glucose concentration, are long-range negatively correlated. By contrast, in diabetic patients, the DFA exponent alpha = 1.65 +/- 0.30 is significantly (P < 0.05) higher than that in nondiabetic subjects, evidencing a breakdown of the long-range negative correlation. It is suggested that the emergence of such positive long-range glucose correlations in diabetic patients-indicating that the net effects of the flux and reflux persist for many hours-likely reflects pathogenic mechanisms of diabetes, i.e., the lack of long-term stability of blood glucose and that the long-range negatively correlated glucose dynamics are functional in maintaining normal glucose homeostasis.     

D(1) dopamine receptor regulation of NHE3 during development in spontaneously hypertensive rats

To determine if the defective interactions among D(1)-like receptors, G proteins, and Na(+)/H(+) exchanger 3 (NHE3) are consequences of hypertension, we studied these interactions in rats, before (2--3 wk) and after (12 wk) the establishment of hypertension. To eliminate the confounding influence of second messenger action on D(1) receptor-NHE3 interaction, studies were performed in renal brush-border membranes (BBM) devoid of cytoplasmic second messengers. NHE3 activity increased with age in Wistar-Kyoto (WKY) rats (3 wk = 1.48 +/- 0.39, n = 13; 12 wk = 2.83 +/- 0.15, n = 16, P < 0.05) but not in spontaneously hypertensive rats (SHRs; 3 wk = 2.52 +/- 0.37, n = 11; 12 wk = 2.81 +/- 0.20, n = 16). D(1) receptor protein tended to decrease, whereas NHE3 protein tended to increase with age in both WKY and SHRs. However, the inhibitory effect of a D(1)-like agonist, SKF-81297, on NHE3 activity increased with age in WKY rats (3 wk = -40.7 +/- 5.3%, n = 10, 12 wk = -58.7 +/- 4.6%, n = 12, P < 0.05) but not in SHRs (3 wk = -27.6 +/- 5.9%, n = 11, 12 wk = -25.1 +/- 3.2%, n = 11). The decreased inhibitory effect of another D(1)-like agonist, fenoldopam, on NHE3 activity in SHRs was not caused by increased activity and binding of G beta gamma to NHE3 as has been reported in young WKY rats. G(s)alpha mediates, in part, the inhibitory effect of D(1)-like agonists on NHE3 activity. In WKY rats, fenoldopam increased G(s)alpha/NHE3 binding to the same extent in 2-wk-old (1.5-fold, n = 4) and adult (1.5-fold, n = 4) rats. In contrast, in SHRs, fenoldopam decreased the amount of G(s)alpha bound to NHE3 in 2-wk-old SHRs and had no effect in 4-wk-old and adult SHRs. These studies indicate that the decreased inhibitory effect of D(1)-like agonists on NHE3 activity in SHRs (compared with WKY rats) precedes the development of hypertension. This may be caused, in part, by a decreased interaction between G(s)alpha and NHE3 in BBM secondary to impaired D(1)-like receptor function.     

Hematological, protein electrophoresis and cholinesterase values of free-living nestling peregrine falcons in Spain

Protein electrophoresis, hematological and cholinesterase values were determined in 32 nestling free-living peregrine falcons (Falco peregrinus) (15- to 27-days-old) in order to establish normal reference values for this population. The following values (mean +/- SD) were observed: prealbumin 0.31 +/- 0.04 g/dl, albumin 1.25 +/- 0.06 g/dl, alpha1 and alpha2-globulin 0.23 +/- 0.02 and 0.16 +/- 0.02 g/dl respectively, beta-globulin 1.02 +/- 0.05 g/dl, gamma-globulin 0.060 +/- 0.08 g/dl, total protein 3.79 +/- 0.18 g/dl, 21.26 +/- 1.30 white blood cells/microl (1 x 10(3)), 2.17 +/- 0.07 red blood cells/microl (1 x 10(6)), packed cell volume 37.58 +/- 0.82%, hemoglobin 20.96 +/- 0.29 g/dl, heterophils 61.14 +/- 2.50% and cholinesterase 1,184 +/- 75 IU/L. There were no difference in any of these parameters among males and females. The hematological values obtained could be considered as representative values in free-living nestling peregrine falcons.