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PubMed1986

Haptoglobin-haemoglobin complex in human plasma inhibits endothelium dependent relaxation: evidence that endothelium derived relaxing factor acts as a local autocoid.

Endothelium dependent relaxation of isometrically mounted rabbit aortic strip preparations was rapidly inhibited by human plasma at dilutions down to 1:1000. Gel filtration and ion exchange chromatography were used to demonstrate that this inhibitory activity was present in fractions containing haptoglobin. Purified haptoglobin itself possessed no inhibitory action against endothelium dependent relaxation, but the haptoglobin-haemoglobin complex did, consistent with the documented ability of haemoglobin to inhibit this phenomenon. The concentration of haemoglobin normally bound to haptoglobin is sufficient to account for the inhibitory properties of human plasma. This suggests that endothelium derived relaxing factor exerts no downstream intravascular effect in vivo and thus that its physiological dilator role is that of a local autocoid acting on subjacent smooth muscle.

Animals↗
PubMed2006

Correlation of primary relaxations and high-frequency modes in supercooled liquids. II. Evidence from spin-lattice relaxation weighted stimulated-echo spectroscopy.

Using spin-lattice relaxation weighted stimulated-echo spectroscopy, we report evidence for a correlation of the primary and secondary relaxation times. The experiments are performed using deuteron nuclear magnetic resonance somewhat above the calorimetric glass-transition of ortho-terphenyl, D-sorbitol, and cresolphthalein-dimethylether. The data analysis is based on the procedure outlined in the accompanying theoretical paper [B. Geil, G. Diezemann, and R. Böhmer, Phys. Rev. E 74, 041504 (2006)]. Direct experimental evidence for a modified spin-lattice relaxation is obtained from measurements on a methyl deuterated acetyl salicylic acid glass. The limitations of the present experimental method are discussed.

Journal Article↗
PubMedDate not supplied

A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms from 1-100 MHz: dependence on tissue type, NMR frequency, temperature, species, excision, and age.

The longitudinal (T1) and transverse (T2) hydrogen (1H) nuclear magnetic resonance (NMR) relaxation times of normal human and animal tissue in the frequency range 1-100 MHz are compiled and reviewed as a function of tissue type, NMR frequency, temperature, species, in vivo versus in vitro status, time after excision, and age. The dominant observed factors affecting T1 are tissue type and NMR frequency (V). All tissue frequency dispersions can be fitted to the simple expression T1 = AVB in the range 1-100 MHz, with A and B tissue-dependent constants. This equation provides as good or better fit to the data as previous more complex formulas. T2 is found to be multicomponent, essentially independent of NMR frequency, and dependent mainly on tissue type. Mean and raw values of T1 and T2 for each tissue are tabulated and/or plotted versus frequency and the fitting parameters A, B and the standard deviations determined to establish the normal range of relaxation times applicable to NMR imaging. The mechanisms for tissue NMR relaxation are reviewed with reference to the fast exchange two state (FETS) model of water in biological systems, and an overview of the dynamic state of water and macromolecular hydrogen compatible with the frequency, temperature, and multicomponent data is postulated. This suggests that 1H tissue T1 is determined predominantly by intermolecular (possibly rotational) interactions between macromolecules and a single bound hydration layer, and the T2 is governed mainly by exchange diffusion of water between the bound layer and a free water phase. Deficiencies in measurement techniques are identified as major sources of data irreproducibility.

Adipose Tissue↗
PubMed1989

Relaxations to endothelium-derived relaxing factor and the metabolite of molsidomine, SIN-1, in the aorta and the hindquarters of the rat.

The effects of SIN-1 were studied on isolated aortic rings and perfused hindquarters of the rat and were compared with the effects of nitroglycerin and endothelium-derived relaxing factor (EDRF) released by acetylcholine or histamine (aorta) and carbachol (hindquarters). SIN-1 relaxes rat aortic rings in a dose-dependent and endothelium-independent way. Aortic rings made tolerant to nitroglycerin in vitro show cross-tolerance to isosorbide dinitrate but no cross-tolerance to EDRF, sodium nitroprusside, or SIN-1. Aortic rings made tolerant to nitroglycerin by in vivo treatment show an important cross-tolerance to isosorbide dinitrate, a small degree of tolerance to sodium nitroprusside, but no significant tolerance to SIN-1 or EDRF. Also, in the nitroglycerin-tolerant hindquarter vasculature, no cross-tolerance is found to EDRF or SIN-1. In the aorta of renal hypertensive rats, in which the relaxation to EDRF-dependent dilators is impaired, no depression of the maximal response to SIN-1 occurs.

Animals↗
PubMed1985

[Left ventricular relaxation property evaluated by isovolumic relaxation flow].

The blood flow recorded in the center of the left ventricle (LV) during the isovolumic relaxation period, i.e., isovolumic relaxation flow (IRF), was evaluated by pulsed Doppler echocardiography. The subjects consisted of 17 normal persons, 12 patients with angina pectoris (AP), 63 with old myocardial infarction (OMI), 16 with hypertrophic cardiomyopathy (HCM) and 16 with dilated cardiomyopathy (DCM). In the normal subjects, the IRF showed a laminar flow and it was directed from the center of the LV toward the apex. The maximum velocity of the IRF coincided with the second heart sound. In the patients with heart diseases, the IRF was classified into three patterns. Type A, in which the IRF was directed toward the apex of the LV: This pattern was observed in two different patient groups from the standpoint of LV wall motion and LV ejection fraction (LVEF). One group had either a normal LVEF without wall motion abnormalities or normal LVEF with a small area of abnormal wall motion in the anterior and/or apical portions. The other group had various LVEF with abnormalities of wall motion in the posterior and/or inferior portions. The duration of the IRF in type A was prolonged in AP (142 +/- 35 msec), OMI (152 +/- 14 msec), HCM (166 +/- 33 msec) and DCM (171 msec) when compared with those of the normal subjects (119 +/- 35 msec). The acceleration time (time interval from the beginning of the IRF to the point of the maximum flow velocity) in the normal subjects was 25 +/- 8 msec, but they were prolonged in AP (37 +/- 12 msec), OMI (59 +/- 22 msec), HCM (64 +/- 18 msec) and DCM (58 msec). The acceleration rate (increment of the flow velocities per sec) was significantly decreased in AP (8.9 +/- 3.2 m/sec2), OMI (4.5 +/- 2.7 m/sec2), HCM (4.5 +/- 1.1 m/sec2) and DCM (3.7 m/sec2) when compared with those of the normal subjects (12.6 +/- 4.0 m/sec2). Type B, in which the IRF was directed away from the LV center to the base of the LV: The patients with this type had slightly depressed LVEF with moderately extended abnormalities of wall motion in the anterior and/or apical portions. Type C without discernible IRF: The patients with this type had severely depressed LVEF with generalized abnormalities of wall motion. It was concluded that the patterns of the IRF are affected by regional wall motion and the IRF seems to be caused by LV relaxation.

Angina Pectoris↗
PubMed1984

[The nature of a covalent bond between the relaxation protein and ColE1-DNA in the relaxation complex].

O-[32P]phosphoserine was found to be the only phosphoamino acid in the acid hydrolysate of the [32P]ColE1 DNA-peptide produced by action of proteases on the ColE1 DNA relaxation complex. This finding suggests that the relaxation protein is bound to ColE1 DNA in the relaxation complex via a phosphodiester linkage between a serine hydroxyl of the protein and the 5'-phosphate of the terminal deoxycytidine residue of the DNA.

Bacterial Proteins↗
PubMed1981

Autonomic responses to stress: the effects of progressive relaxation, the relaxation response, and expectancy of relief.

Forty-eight male subjects with no previous meditative experience engaged in either progressive relaxation (PR), a meditative treatment designed to induce the relaxation response (RR), or a no-treatment control experience (C) during four sessions on consecutive days. Negative expectations regarding the effectiveness of each technique for reducing physiological responses to stress were induced for half of the subjects in each treatment condition, and positive expectations were induced for the other half. Subjects viewed a stressful film following practice of their technique during the first and fourth sessions. Heart rate and electrodermal responding were recorded continuously during practice of the techniques and during the stressful film throughout the first and fourth sessions. Results indicated lowered heart rate levels prior to the film for subjects in the PR-positive expectancy condition and during the film for subjects in the RR-positive expectancy condition. It is suggested that subjects' expectancies concerning meditation may affect cardiovascular responding during stress, although meditative treatments in general do not appear to reduce stress responding as effectively as previously suggested.

Adolescent↗
PubMed2006

Relaxation strategies and enhancement of hypnotic susceptibility: EEG neurofeedback, progressive muscle relaxation and self-hypnosis.

Hypnosis has been shown to be efficacious in a range of clinical conditions, including the management of chronic pain. However, not all individuals are able to enter a hypnotic state, thereby limiting the clinical utility of this technique. We sought to determine whether hypnotic susceptibility could be increased using three methods thought to facilitate relaxation, with particular interest in an EEG neurofeedback protocol which elevated the theta to alpha ratio. This was compared with progressive muscle relaxation and self-hypnosis. Ten subjects with moderate levels of susceptibility (2-7/12) were randomly assigned to each condition and assessed for hypnotic susceptibility prior to and upon completion of 10 sessions of training. Hypnotic susceptibility increased post-training in all groups, providing further evidence that operant control over the theta/alpha ratio is possible, but contrary to our predictions, elevation of the theta/alpha ratio proved no more successful than the other interventions. Nonetheless, all three techniques successfully enhanced hypnotic susceptibility in over half of the participants (17/30), a similar incidence to that reported using other methods. As previously reported, the majority who were not susceptible to modification were at the lower levels of susceptibility, and the greater increases tended to occur in the more susceptible subjects. However, here enhancement was disclosed in some at low levels, and capability was found of reaching high levels, both features not typically reported. Further research is warranted.

Adult↗
PubMed1998

Muscle relaxant action of MS-322, a new centrally acting muscle relaxant, in rats.

1. The pharmacological properties of (R)-(+)-3-phenyl-5-¿2-(1-pyrrolidinylmethyl)-butyryl¿isoxazole hydrochloride (MS-322) were investigated and compared with those of other muscle relaxants. 2. MS-322 (3-12 mg/kg, IV) reduced spinal reflex potentials in acutely spinalized rats dose dependently. Its inhibitory effects on polysynaptic and dorsal root reflexes were more marked than those on the monosynaptic reflex. 3. MS-322 (1.5-12.0 mg/kg, IV) depressed the afferent discharges of de-efferented muscle spindles in anesthetized rats dose dependently. 4. The inhibitory effect of MS-322 on this afferent activity was considered to be due to its membrane stabilizing action. 5. In addition to the central effects of MS-322, its effect on muscle spindles may contribute to its muscle relaxant activity.

Animals↗
PubMed2004

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo.

RATIONALE: The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered. OBJECTIVE: This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo. METHODS: Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers ( n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo. RESULTS: Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response. CONCLUSIONS: Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.

Adult↗
PubMed1992

Sodium-23 and potassium-39 nuclear magnetic resonance relaxation in eye lens. Examples of quadrupole ion magnetic relaxation in a crowded protein environment.

Single and multiple quantum nuclear magnetic resonance (NMR) spectroscopic techniques were used to investigate the motional dynamics of sodium and potassium ions in concentrated protein solution, represented in this study by cortical and nuclear bovine lens tissue homogenates. Both ions displayed homogeneous biexponential magnetic relaxation behavior. Furthermore, the NMR relaxation behavior of these ions in lens homogenates was consistent either with a model that assumed the occurrence of two predominant ionic populations, "free" and "bound," in fast exchange with each other or with a model that assumed an asymmetric Gaussian distribution of correlation times. Regardless of the model employed, both ions were found to occur in a predominantly "free" or "unbound" rapidly reorienting state. The fraction of "bound" 23Na+, assuming a discrete two-site model, was approximately 0.006 and 0.017 for cortical and nuclear homogenates, respectively. Corresponding values for 39K+ were 0.003 and 0.007, respectively. Estimated values for the fraction of "bound" 23Na+ or 39K+ obtained from the distribution model (tau C greater than omega L-1) were less than or equal to 0.05 for all cases examined. The correlation times of the "bound" ions, derived using either a two-site or distribution model, yielded values that were at least one order of magnitude smaller than the reorientational motion of the constituent lens proteins. This observation implies that the apparent correlation time for ion binding is dominated by processes other than protein reorientational motion, most likely fast exchange between "free" and "bound" environments. The results of NMR visibility studies were consistent with the above findings, in agreement with other studies performed by non-NMR methods. These studies, in combination with those presented in the literature, suggest that the most likely role for sodium and potassium ions in the lens appears to be the regulation of cell volume by affecting the intralenticular water chemical potential.

Animals↗
PubMed2001

Nuclear magnetic resonance relaxation in determination of residue-specific 15N chemical shift tensors in proteins in solution: protein dynamics, structure, and applications of transverse relaxation optimized spectroscopy.

We developed several approaches to direct determination of the 15N CSA from relaxation measurements in uniformly 15N-labeled proteins in solution. These methods are based on multiple-field measurements and could be extended to other nuclei in proteins and other molecules. Combined with the isotropic chemical shift measurements, this provides an experimental approach to full characterization of chemical shift tensors in proteins in their native milieu, which is likely to provide valuable information on the nature of chemical shifts and their relation to protein structure. Knowledge of 15N CSA is essential for an accurate characterization of protein dynamics from relaxation measurements.

Anisotropy↗
PubMed2006

Condensed-phase relaxation of multilevel quantum systems. II. Comparison of path integral calculations and second-order relaxation theory for a nondegenerate three-level system.

An exactly solvable model of multisite condensed-phase vibrational relaxation was studied in Paper I (Peter, S.; Evans, D. G.; Coalson, R. D. J. Phys. Chem. B 2006, 110, 18758.), where it was shown that long-time steady-state site populations of a degenerate N-level system are not equal (hence, they are non-Boltzmann) and depend on the initial preparation of the system and the number of sites that it comprises. Here we consider a generalization of the model to the case of a nondegenerate three-level system coupled to a high-dimensional bath: such a model system has direct relevance to a large class of donor-bridge-acceptor electron transfer processes. Because the quantum dynamics of this system cannot be computed analytically, we compare numerically exact path integral calculations to the predictions of second-order time-local relaxation theory. For modest system-bath coupling strengths, the two sets of results are in excellent agreement. They show that non-Boltzmann long-time steady-state site populations are obtained when the level splitting is small but nonzero, whereas at larger values of the system bias (asymmetry) these populations become Boltzmann distributed.

Journal Article↗
PubMed1993

Sumatriptan relaxes isolated porcine ophthalmic artery, but inhibits VIP-induced relaxation.

Sumatriptan, a 5-hydroxytryptamine (5HT)1-like receptor agonist, is a new antimigraine drug which is also effective in cluster headache (CH), a disorder with marked ocular circulatory abnormalities. Sumatriptan could putatively exert a therapeutic effect in this vascular bed. The present study is an attempt to assess sumatriptan's vasoactivity in isolated porcine ophthalmic artery (POA) and to verify whether it has similar activity to 5HT, and whether it interferes with the vasodilation induced by calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP). In contrast to 5HT, sumatriptan induced only slight contraction in POA at high concentrations. However, in some artery segments pre-contracted with PGF2 alpha, sumatriptan induced a slight and short-lasting but marked relaxation. In addition, relaxations induced by VIP were inhibited significantly by sumatriptan, whereas CGRP effects were not influenced by the drug. Such reactions suggest that sumatriptan's effect in CH is probably unrelated to direct ocular arterial vasoconstriction.

Animals↗
PubMed2005

Surface relaxation and chemical exchange in hydrating cement pastes: a two-dimensional NMR relaxation study.

We report the first nuclear magnetic resonance (NMR) two-dimensional correlation T(1) - T(2) and T(2) - T(2) measurements of hydrating cement pastes. A small but distinct cross peak in the two-dimensional relaxation spectrum provides the first direct evidence of chemical exchange of water between gel and capillary pores occurring over the first 14 days of hydration. A correlation of features along the line T(1) = 4T(2) provides strong supportive evidence for the surface diffusion model of (1)H nuclear spin relaxation in cements and for a multimodal discrete pore size distribution. Differences in detail of the results are reported for white cement paste and white cement paste with added silica fume. Both the method and the theory presented can be applied more widely to other high surface area materials with other reactive surface areas.

Journal Article↗
PubMed1989

Failure of transient lower oesophageal sphincter relaxation in response to gastric distension in patients with achalasia: evidence for neural mediation of transient lower oesophageal sphincter relaxations.

Transient lower oesophageal sphincter relaxation (LOSR) is the major mechanism underlying gastro-oesophageal reflux. The mediation and control of LOSRs are incompletely understood but evidence suggests a neural inhibitory mechanism. In this study we have evaluated the effect of gastric distension on LOS function in 16 patients with untreated idiopathic achalasia and compared it with that in 10 healthy controls. With the subjects sitting, the stomach was distended with a liquid mixture that generated 750 ml CO2. Oesophageal pH and motility were monitored for 10 minutes before and after distension. In normal controls, gastric distension induced a four-fold increase in the rate of LOSRs and gas reflux episodes (as evidenced by oesophageal common cavities), whereas this response was absent in the achalasia patients. Basal LOS pressure did not change in either group. These findings are consistent with the notion that transient LOSRs induced by gastric distension are neurally mediated, probably by the same inhibitory nerves that govern swallow mediated LOS relaxation.

Adolescent↗
PubMed2001

Left ventricular relaxation abnormality is detectable by analysis of the relaxation time constant in patients with atrial fibrillation.

Left ventricular (LV) contractility is constantly changing during atrial fibrillation (AF), which is dependent on the force-interval relationships. However, no information has been available on LV relaxation in patients with both AF and impaired LV systolic function. LV pressure was measured with a catheter-tipped micromanometer and the time constant of isovolumic LV pressure decline (tau(bf)) was calculated with best exponential fitting from more than 10 consecutive beats. Patients with AF (5 with mitral valvular disease, 6 with idiopathic dilated cardiomyopathy, and 1 with no underlying disease) were subdivided into 2 groups: group A, with ejection fraction (EF) <0.5 (n=7); and group B, with EF > or =0.5 (n=5). Linear correlation coefficients (r) between tau and RR2, RR2/RR1, LV peak systolic pressure (peak LVP) were calculated. Although tau did not show a discrepancy between the 2 groups, tau(bf) correlated better with RR2/RR1 only in the group A patients. The relation between tau and peak LVP showed a good correlation with a steep slope (R, Deltatau/Deltapeak LVP) only in the group A patients (accentuated afterload-dependence). R was significantly different between the 2 groups. Thus, a beat-to-beat analysis of tau may be a practical and feasible way for detecting LV relaxation abnormality in patients with AF.

Adult↗