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Respiration and heat in contracting and non-contracting dissipative muscle.

The oxygen consumption-heat relationship is analyzed using a scheme of reactions underlying muscle aerobic metabolism. The enzymatic chemical reactions of the scheme are considered near equilibrium during a contraction, and far from equilibrium during energy dissipation in a non-contracting state. Implications show that for two different metabolic rates, the proportionality between oxygen consumption and heat is a very specific case, because of restricting necessary conditions.

Animals↗

[Aggregation of isolated myofibrils stimulated by their contraction. I. Origin of the second phase of optical changes during myofibril contraction].

Aggregation of contracted myofibrils was shown to be responsible for spontaneous: slow reduction of optical density of myofibril suspension on the final stage of their contraction. This effect faded with an increase in light wavelength, with increased angle of view of the photocell and diminished sizes of myofibrils.

Actomyosin↗

Participation of Na+ in the excitation-contraction coupling of the phasic and tonic contractions in stomach smooth muscles.

The sucrose gap method was used to study the effect of Na+ on the electrical and contractile activity of smooth-muscle strips from the antrum and fundus of cat stomach. Na+ reduction or elimination from the nutrient medium leads to reduction of the depolarization phase of the plateau-action potentials and to a transient increase in the amplitude of the phasic contractions of the antrum, followed by their complete disappearance. In Na-free medium direct electrical stimulation leads not to the appearance of plateau-action potentials, but of a group of Ca2+-dependent spike-potentials and high-amplitude phasic contractions. In fundic preparations the decrease in the Na+-concentration of the nutrient solution results in a gradual rise of the tonic tension, without appearance of action potentials. This effect of the reduced Na+ is inhibited by Ca-antagonists La3+ (10(-2) mol/l) D 600 (10(-6) - 10(-5) mol/l) and by sodium nitroprusside (10(-6) mol/l). On the other hand, an increase in the Ca-conductivity of the membrane of the fundic smooth muscle cells was observed in Na+-free medium. It is assumed that at the level of the fundic smooth muscle cell membrane there is competition between Na+ and Ca2+ with respect to slow Ca-channels.

Action Potentials↗

Vascular contraction and relaxation to thrombin and trypsin: thrombomodulin preferentially attenuates thrombin-induced contraction.

Thrombin and trypsin activate protease-activated receptors (PARs) that modulate vascular tone. In addition to the PARs, thrombin also binds to thrombomodulin via exosite 1, a domain also involved in the interaction of thrombin with PAR-1 but not PAR-2. The purpose of this study was to determine whether thrombomodulin would alter thrombin-induced vasoconstriction, thought to be mediated predominantly by PAR-1, but not PAR-2, which mediates vascular relaxation. For comparison, thrombomodulin was examined for its effect on both thrombin and trypsin-induced responses. Trypsin was 2000-fold more potent as a relaxant than as a contractile peptide, whereas thrombin was only 7.8-fold more potent as a relaxant than contractile agonist, consistent with activation of PAR-1 predominantly mediating contraction and PAR-2 predominantly mediating relaxation. Although thrombomodulin (10(-7) M) alone did not alter vascular tone or the rate of thrombin-induced vascular responses, thrombomodulin (10(-8) and 10(-7) M) attenuated maximal thrombin (10(-8) and 10(-7) M)-induced vasoconstriction preferentially compared with thrombin-induced relaxation and had no effect on equieffective trypsin-induced responses. The inhibition of thrombin-induced contraction resulted from the interaction of thrombin with thrombomodulin rather than any direct effect of thrombomodulin on tissue PARs. Thus, this study describes a novel vascular action of thrombomodulin to selectively attenuate thrombin-induced vascular contractility. This action of thrombomodulin may serve to protect vasculature from thrombin-induced vasoconstriction during conditions of endothelial injury known to increase plasma and cellular levels of thrombomodulin.

Animals↗

Surface contraction and expansion waves correlated with differentiation in axolotl embryos. II. In contrast to urodeles, the anuran Xenopus laevis does not show furrowing surface contraction waves.

We have observed a number of contraction waves traversing the axolotl (Ambystoma mexicanum) embryo (a urodelan amphibian) from the midblastula transition up to at least neural tube closure, and wished to learn if similar "differentiation waves" appear on the popular laboratory anuran amphibian, the South African clawed toad, Xenopus laevis. Time lapse video microscopy showed that no contraction waves are visible on the surface of Xenopus from gastrulation through neurulation. It is possible that cell intercalations in the double-layered ectoderm of the Xenopus embryo are homologous to the surface waves in the single layered ectoderm of the axolotl embryo. In any case, a simple, universal correspondence between surface waves and induction phenomena and differentiation does not exist.

Ambystoma↗

Nurse managers' perceptions of contracting for nurse education, Part 2: Contracting and post-registration education.

The introduction of the 'purchaser/provider' split into nurse education alters the relationship between service units (or the education purchasers) and colleges of health studies (the education providers). This is the second of two papers, and focuses on senior health service managers views on the purchasing and provision of post-registration nurse education. 24 managers from one region were interviewed. The aim was to identify their post-registration education needs, the criteria they use to choose between post-registration courses held in different colleges, and how they identify 'value for money' in post-registration education. The findings showed a limited understanding of the financial issues involved and considerable variation in opinion regarding the purpose, type and academic level of post-registration education. Cost emerged as a potentially more influential factor than quality in determining which courses managers will purchase. The managers interviewed are predominantly looking to contract with colleges who will be communicative, receptive to their needs, and willing to work in partnership with them.

Attitude of Health Personnel↗

The theory of sliding filament models for muscle contraction. II. Biochemically-based models of the contraction cycle.

A seven-state sliding filament model is proposed which differs from the model of Eisenberg & Greene. It is based on a simplified version of the in-vitro contraction cycle of Stein et al., and also has some desirable dynamical features of the empirical three-state model of Nishiyama & Murase. Appropriate x-dependences for all reaction rates are derived from the transition-state theory. The seventh-state is assumed to be a high-tension intermediate of A.M.ATP, from which direct but x-dependent dissociation can occur. If the final A.M.ATP state has a sufficiently lower tension than that of A.M.ADP.Pi, then the dominant escape path from the intermediate state is shown to be direct dissociation of the actin-myosin bond. This leads to an approximate five-state model for active and relaxed muscle in which A.M and the final A.M.ATP state are omitted.

Actins↗

Long-lasting muscle fatigue: partial disruption of excitation-contraction coupling by elevated cytosolic Ca2+ concentration during contractions.

The repeated elevation of cytosolic Ca(2+) concentration ([Ca(2+)](i)) above resting levels during contractile activity has been associated with long-lasting muscle fatigue. The mechanism underlying this fatigue appears to involve elevated [Ca(2+)](i) levels that induce disruption of the excitation-contraction (E-C) coupling process at the triad junction. Unclear, however, are which aspects of the activity-related [Ca(2+)](i) changes are responsible for the deleterious effects, in particular whether they depend primarily on the peak [Ca(2+)](i) reached locally at particular sites or on the temporal summation of the increased [Ca(2+)] in the cytoplasm as a whole. In this study, we used mechanically skinned fibers from rat extensor digitorum longus muscle, in which the normal E-C coupling process remains intact. The [Ca(2+)](i) was raised either by applying a set elevated [Ca(2+)] throughout the fiber or by using action potential stimulation to induce the release of sarcoplasmic reticulum Ca(2+) by the normal E-C coupling system with or without augmentation by caffeine or buffering with BAPTA. Herein we show that elevating [Ca(2+)](i) in the physiological range of 2-20 microM irreversibly disrupts E-C coupling in a concentration-dependent manner but requires exposure for a relatively long time (1-3 min) to cause substantial uncoupling. The effectiveness of Ca(2+) released via the endogenous system in disrupting E-C coupling indicates that the relatively high [Ca(2+)](i) attained close to the release site at the triad junction is a more important factor than the increase in bulk [Ca(2+)](i). Our results suggest that during prolonged vigorous activity, the many repeated episodes of relatively high triadic [Ca(2+)] can disrupt E-C coupling and lead to long-lasting fatigue.

Animals↗

Alternative splicing, muscle contraction and intraspecific variation: associations between troponin T transcripts, Ca(2+) sensitivity and the force and power output of dragonfly flight muscles during oscillatory contraction.

The flight muscles of Libellula pulchella dragonflies contain a mixture of six alternatively spliced transcripts of a single troponin T (TnT) gene. Here, we examine how intraspecific variation in the relative abundance of different TnT transcripts affects the Ca(2+) sensitivity of skinned muscle fibers and the performance of intact muscles during work-loop contraction regimes that approximate in vivo conditions during flight. The relative abundance of one TnT transcript, or the pooled relative abundance of two TnT transcripts, showed a positive correlation with a 10-fold range of variation in Ca(2+) sensitivity of skinned fibers (r(2)=0.77, P<0.0001) and a threefold range in peak specific force (r(2)=0.74, P<0.0001), specific work per cycle (r(2)=0.54; P<0.0001) and maximum specific power output (r(2)=0.48, P=0.0005) of intact muscle. Using these results to reanalyze previously published data for wing kinematics during free flight, we show that the relative abundances of these particular transcripts are also positively correlated with wingbeat frequency and amplitude. TnT variation alone may be responsible for these effects, or TnT variation may be a marker for changes in a suite of co-regulated molecules. Dragonflies from two ponds separated by 16 km differed significantly in both TnT transcript composition and muscle contractile performance, and within each population there are two distinct morphs that showed different maturational trajectories of TnT transcript composition and muscle contractility. Thus, there is broad intraspecific variability and a high degree of population structure for contractile performance phenotypes, TnT ribotypes and ontogenetic patterns involving these traits that affect locomotor performance.

Alternative Splicing↗

Tetrandrine potentiates caffeine-induced contraction but inhibits phenylephrine-induced contraction in perfused rat mesenteric artery.

Effects of tetrandrine (TET), a bisbenzylisoquinoline alkaloid, on the contractile responses of perfused rat mesenteric arteries to phenylephrine (PE) and caffeine were investigated. TET concentration-dependently (1-30 micro M) attenuated phenylephrine-induced responses but potentiated the contractile responses to caffeine (5-40 mM) in the presence and absence of Ca(2+). Berbamine (BER), a structural analogue of TET, elicited a relatively smaller inhibitory effect on the responses to PE due to Ca(2+) release or Ca(2+) influx. However, both TET and BER elicited a comparable potentiating effect on caffeine-induced contraction. Cyclopiazonic acid (CPA; 10 micro M), a selective sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, mimicked the potentiating effect of TET when added 5 min prior to caffeine in Ca(2+)-free medium. However, CPA did not augment and might even inhibit the caffeine-induced response when it was preincubated with the tissue for 25 min prior to the addition of caffeine. We propose that TET elicits differential effects on PE- and caffeine-induced responses in perfused rat mesenteric arterial bed. The inhibitory effect of TET on PE-induced responses is probably due to its direct interactions with alpha-adrenoceptors and PE-sensitive Ca(2+)-channels. The augmentation of caffeine-induced responses by TET, particularly in Ca(2+)-free medium, is likely to be due to its partial inhibition of the sarcoplasmic reticulum Ca(2+)-ATPase pump.

Alkaloids↗

A histological comparison of contracted and non-contracted capsules around silicone breast implants.

A single blind comparison of capsular tissue obtained from both breasts from 7 patients in whom unilateral contracture had occurred leads to the following conclusions: (1) The presence of droplets (presumed to be silicone, or extractable silicone as identified by IR) in capsular tissue does not correlate with the clinical finding of firmness. (2) Contracted capsules are apt to be significantly more cellular, largely as a result of an increased fibroblast population. (3) The apparent severity of inflammation in a biopsy of a capsule does not correlate with the clinical degree of firmness in the breast. (4) In the 7 cases studied, capsule thickness or vascularity, collagen alignment, staining uptake, presence of foreign bodies, or presence of an inner cell layer of macrophages did not correlate with the clinical finding of firmness.

Breast↗

ATP-sensitive K+ channels mediate alpha 2D-adrenergic receptor contraction of arteriolar smooth muscle and reversal of contraction by hypoxia.

Evidence in rat skeletal muscle suggests that local metabolic control of blood flow is facilitated by the reliance on alpha 2D-adrenergic receptors (ARs) for constriction of arterioles, together with the strong sensitivity of this constriction to inhibition by hypoxia. The present study examined the role of ATP-sensitive K+ (KATP) channels in the selective interaction between alpha 2D-ARs and hypoxia. Arterioles from rat cremaster muscle that possess both alpha 1D (alpha 1A/D)- and alpha 2D-AR subtypes were microcannulated, pressurized, and isolated in a tissue bath for measurement of changes in lumen diameter. Three studies first examined whether stimulation of alpha 2D- and alpha 1D-ARs involves inhibition of the KATP channel. Concentration-dependent constriction by the KATP antagonists glibenclamide (GLB, 0.01 to 10 mumol/L) and disopyramide (0.001 to 1 mmol/L) were abolished during alpha 2D stimulation but unaffected during alpha 1D stimulation. Activation of the KATP channel by cromakalim inhibited alpha 2D constriction with greater potency than alpha 1D (EC50, 7.0 +/- 0.2 versus 6.3 +/- 0.1). Finally, GLB (0.5 mumol/L) abolished dose-dependent alpha 2D constriction, whereas alpha 1D was unaffected. These data suggest that alpha 2D but not alpha 1D stimulation is "coupled" with closure of the KATP channel, leading to depolarization and contraction of vascular smooth muscle. In a second series, hypoxic (PO2, 6 mm Hg) inhibition of intrinsic smooth muscle tone was completely reversed by 0.1 mumol/L GLB, concentration-dependent GLB constriction was enhanced during hypoxia, and hypoxia reversed GLB constriction. These data confirm reports by others that hypoxia potentiates the activation of KATP channels, leading to hyperpolarization and relaxation. Finally, GLB constriction, which was abolished by concomitant alpha 2D stimulation, was completely restored by simultaneous activation of KATP channels with hypoxia. These findings suggest that the sensitivity of alpha 2D-AR constriction to inhibition by hypoxia arises through "antagonistic coupling" between these two stimuli, by which the alpha 2D-AR inhibits and hypoxia activates KATP channels.

Adenosine Triphosphate↗

[Prevalence of mitral valve prolapse in patients with premature ventricular contractions and the relationship between the prolapse and the types of premature contractions].

To assess the prevalence of mitral valve prolapse (MVP) in patients with premature ventricular contractions (PVCs), 109 patients with PVCs (M: 69, F: 40, 42 +/- 20 years; mean +/- SD) and 50 control subjects (M: 38, F: 12, 47 +/- 10 years) were studied by echocardiography. MVP was diagnosed by two-dimensional echocardiography. The criterion for mitral valve prolapse by two-dimensional echocardiography is extension of the mitral leaflet to the left atrial side beyond the plane of the mitral annulus. In addition, 60 patients with PVCs were examined by 24-hour Holter ECG and scored by the Lown's classification. Results were as follows: 1) MVP was detected more frequently in patients with PVCs than in the control subjects (22/109, 20% vs 3/50, 6%, p less than 0.05) by echocardiography. 2) PVC patients with MVP were significantly younger than patients without MVP (34 +/- 14 vs 47 +/- 21 yrs, p less than 0.05), but there were no significant differences between these two groups as to sex, left atrial diameter and left ventricular dimension. 3) The 24-hour Holter ECG revealed that the high grade PVCs (Lown grade III & IV) was more closely related to the absence of MVP (20/45, 44% vs 4/11, 36%), though this trend did not reach statistical significance. It was suggested that MVP is not a major determinant of PVC, and life-threatening arrhythmias are more likely related to cases without MVP.

Adult↗

Quality in the dermatological contract. A report from the Workshop on Quality Issues in Dermatological contracting of the British Association of Dermatologists.

This document is a summary of the most important points from a meeting convened by the audit sub-committee of the British Association of Dermatologists (BAD) and the research unit of the Royal College of Physicians on 16 May 1994. Participants represented the views of district general and teaching hospital dermatologists, a fundholding general practitioner, a health commissioning agent and patient support groups. The meeting was preceded by a workshop on 6 April 1994, involving 16 patient support groups chaired by Consumers Association from which a discussion paper was presented by two representatives. This report is intended for dermatologists, contract managers and purchasers.

Dermatology↗