Failure of opioids to affect excitation and contraction in isolated ventricular heart muscle

Summary The opioid agonists morphine (selective for -receptors) and ethylketocyclazocine (selective for kappa-receptors), at concentrations evoking strong effects in neuronal structures, did not significantly affect the configuration of the intracellularly recorded action potential and the force of contraction in ventricular heart muscle isolated from guinea pigs, rabbits and man. These results suggest that any changes of heart functions in vivo in response to opioid-like drugs are probably not mediated postsynaptically at the myocardial cell membrane but rather presynaptically, influencing the release of noradrenaline and/or acetylcholine from the nerve terminals.     

Heritability of locomotor performance and its correlates in a natural population

Summary Locomotor capacities and their physiological bases are thought to be of considerable selective importance in natural populations. Within this functional complex, organismal performance traits (e.g., speed, stamina) are expected to be of more direct selective importance than their suborganismal determinants (e.g., heart size). Quantitative genetics theory predicts that traits of greater selective importance should generally have lower heritabilities at equilibrium. Contrary to these expectations, we report that organismal performance traits had the highest heritabilities in a natural population of garter snakes.     

Effect of cold exposure on electrophysiological properties of rat heart

Male rats exposed to the cold (4°C) for five or ten days exhibited modifications in their thyroid state, as documented by increases in serum thyroid hormone levels, to which differently graded modifications of heart weight/body weight ratio, heart rate, and resting metabolic rate were associated. The values of the above mentioned thyroid state indicators returned to those of the control when the animals, kept at cold for ten days, were re-exposed to room temperature (24°C) for an additional 10 days. The configuration of action potentials, recorded in vitro at 26°C from fibres of anterior papillary muscles, was different in control rats of different age and was affected by prolonged cold exposure. In fact, the action potential duration (APD) increased after ten days of cold exposure. In the re-exposed group the APD was not different from that of the controls. Such a pattern was not significantly modified when the stimulation frequency increased from 1 Hz to 5 Hz. The above results suggest that in cold exposure, as in experimental hyperthyroidism, thyroid hormone might exert a cardiac chronotropic effect by modifying heart electrophysiological properties. Thus thyroid hormone should play a basic role during the exposure to cold environment, stimulating the body metabolism and increasing heart rate as a response to the requirement for greater tissue perfusion.     

An insect acetylcholinesterase inhibitor from compound eyes of Triatoma infestans (Hemiptera)

The presence of an acetylcholinesterase inhibitor in the compound eyes of adult Triatoma infestans was demonstrated. The inhibitory activity was localized in the ocular pigments separated by disc gel electrophoresis. The inhibitor was selective against insect acetylcholinesterase, reversible, noncompetitive and heart stable.     

Realism on the rocks: Novel success and James Hutton's theory of the earth

In this paper, I introduce a new historical case study into the scientific realism debate. During the late-eighteenth century, the Scottish natural philosopher James Hutton made two important successful novel predictions. The first concerned granitic veins intruding from granite masses into strata. The second concerned what geologists now term “angular unconformities”: older sections of strata overlain by younger sections, the two resting at different angles, the former typically more inclined than the latter. These predictions, I argue, are potentially problematic for selective scientific realism in that constituents of Hutton's theory that would not be considered even approximately true today played various roles in generating them. The aim here is not to provide a full philosophical analysis but to introduce the case into the debate by detailing the history and showing why, at least prima facie, it presents a problem for selective realism. First, I explicate Hutton's theory. I then give an account of Hutton's predictions and their confirmations. Next, I explain why these predictions are relevant to the realism debate. Finally, I consider which constituents of Hutton's theory are, according to current beliefs, true (or approximately true), which are not (even approximately) true, and which were responsible for these successes.     

Direct toxic effect of isoproterenol on cultured cardiac muscle cells

Summary Isoproterenol at relatively high doses (2.5 mg/ml) has a marked toxic effect on rat heart muscle cells cultivated in vitro. This effect is not prevented by propranolol and therefore is not mediated by beta adrenergic receptors.This work has been supported in part by a grant from the Muscular Dystrophy Association, Inc. to Prof. M. Aloisi.     

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin light-chain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed.     

Transmural pressure as a determinant of basic intrinsic heart rate

Summary It was observed the heart rate was minimum at zero transmural pressure. The mean heart rate at zero transmural pressure was 23±5/min. This mean heart rate increased from 23±5/min to a peak value of 40±6/min (74% acceleratin) when the transmural pressure was raised from 0 to +4 mm Hg and to a similar peak value of 36±8/min (56% acceleration) when the transmural pressure was lowered from 0 to –4 mm Hg. The peak values attained at ±4 mm Hg were higly significant (p<0.001). It is concluded that the heart rate at zero transmural pressure represents the basic intrinsic pacemaker frequency independent of neural, humoral, thermal and haemodynamically induced mechanical influences.     

Pimozide and pyrogen-induced fever in rabbits

Summary Pimozide, a selective blocker of DA receptors, partly inhibits but does not suppress either the DA-induced hyperthermia or the LPS-induced fever in rabbits. This suggests that a common DA-related mechanism could be at least partly involved in both responses.Acknowledgments. We wish to thank Laboratories Le Brun (Paris) for the generous supply of pimozide.     

What’s new in the renin-angiotensin system?

The type 1 angiotensin receptor (AT(1)) activates an array of intracellular signalling pathways that control cell and tissue responses to the peptide hormone angiotensin II (AngII). The capacity of AT(1) receptors to initiate and maintain such signals has typically been explained on the basis of conventional heterotrimeric guanine nucleotide binding protein (G protein) activation, specifically G(q/11). Accumulating evidence from studies utilising a variety of AT(1) receptor mutants and AngII analogues indicates that some important downstream effects of AT(1) receptors are independent of classical G protein coupling. Importantly, AT(1) receptor-mediated endocytosis, tyrosine phosphorylation signalling and mitogen-activated protein kinase activation as well as transactivation of the epidermal growth factor receptor can occur in G(q/11)-uncoupled receptor mutants. These observations point to a functional partitioning of AT(1) receptor signals that permits separation of short-term AngII actions (e.g., vasoconstriction) from more extended events, such as pathological cell growth in heart and blood vessels, and may open up new avenues for selective antagonism.     

Selective killing of smooth muscle cells in culture by the ricin A-chain conjugated with monoclonal antibodies to a cell surface antigen via a dextran bridge

Monoclonal antibodies to a surface antigen of the modulated smooth muscle cells originally isolated from the rat aorta media were conjugated with ricin A-chain via an oxidized dextran bridge. The interaction of cultured cells with the conjugates obtained and with control substances was monitored following incorporation of 14C-leucine radioactivity. It was found that 14C-leucine incorporation was suppressed by 80-90% at a conjugate concentration of 10(-6)-10(-7) M. Antigen-negative cells (line IAR; rat hepatocytes) were insensitive to the conjugate at any concentration used. Control use of purified ricin A-chain, native or oxidized dextran, specific and nonspecific IgG did not affect normal 14C-leucine incorporation. The data obtained may be useful for designing targeted drug transport systems and for selective screening of modulated smooth cells in vascular pathology models in vivo.     

Innervation and control of the heart of a gastropod,Rapana

Summary The innervation and control of the heart of a prosobranch mollusc,Rapana thomasiana, were studied. Acetylcholine was found to be an inhibitory neurotransmitter. Both serotonin and FMRFamide (Phe-Met-Arg-Phe-NH₂) showed excitatory effects on the heart; FMRFamide had greater inotropic and more regulatory chronotropic effects than serotonin. The effects of serotonin were blocked by methysergide, while the effects of FMRFamide and of stimulating the excitatory cardiac nerves were not blocked. Stimulation of circumesophageal ganglia elicited a slow enhancement of heart beat together with body movement. This enhancement was blocked by methysergide. Serotonin was considered to act at the heart as a local neurohormone. Although the mechanism of action of FMRFamide is still not yet clarified, it is possible that FMRFamide plays a physiological role as a cardioregulatory substance, as indicated by the physiological and histological findings.     

Hybridizing kernel‐based fuzzy c‐means with hierarchical selective neural network ensemble model for business failure prediction

More and more ensemble models are used to forecast business failure. It is generally known that the performance of an ensemble relies heavily on the diversity between each base classifier. To achieve diversity, this study uses kernel‐based fuzzy c‐means (KFCM) to organize firm samples and designs a hierarchical selective ensemble model for business failure prediction (BFP). First, three KFCM methods—Gaussian KFCM (GFCM), polynomial KFCM (PFCM), and Hyper‐tangent KFCM (HFCM)—are employed to partition the financial data set into three data sets. A neural network (NN) is then adopted as a basis classifier for BFP, and three sets, which are derived from three KFCM methods, are used to build three classifier pools. Next, classifiers are fused by the two‐layer hierarchical selective ensemble method. In the first layer, classifiers are ranked based on their prediction accuracy. The stepwise forward selection method is employed to selectively integrate classifiers according to their accuracy. In the second layer, three selective ensembles in the first layer are integrated again to acquire the final verdict. This study employs financial data from Chinese listed companies to conduct empirical research, and makes a comparative analysis with other ensemble models and all its component models. It is the conclusion that the two‐layer hierarchical selective ensemble is good at forecasting business failure.     

Potentiation by taurine of the inotropic effect of ouabain and the content of intracellular Ca++ and taurine in the heart.

Under certain conditions, taurine (3.0mM) potentiated cardiac contractile response to ouabain in the normal medium. The potentiation by taurine was also observed in the low K+ medium, in which the positive inotropic effect of ouabain increased. The potentiation as seen in both media was, at least in part, due to the increase by taurine of Ca++ content in the heart. Taurine in the heart was not directly related to this potentiation.     

Depletion of hypothalamic norepinephrine reduces the fever induced by polyriboinosinic acid: polyribocytidylic acid (Poly I:Poly C) in rats

Administration of either Poly I:Poly C (0.05-0.50 micrograms) or norepinephrine (2-8 micrograms) into the anterior hypothalamic area produced a dose-related fever in rats. The fever induced by Poly I:Poly C was attenuated after selective depletion of norepinephrine in the hypothalamus. However, selective depletion of hypothalamic norepinephrine did not affect the fever induced by intrahypothalamic norepinephrine. The data indicate that Poly I:Poly C may act to induce fever through the endogenous release of norepinephrine from the rat's hypothalamus.     

Effect of insulin in vivo on the synthesis of free fatty acids (FFA) in chicken heart and skeletal muscle

Summary The effect of insulin on the synthesis of free fatty acids from glucose in the skeletal and heart muscles of chicken is examined. 10 min after glucose-(U-¹⁴C) administration, labeled free fatty acids (FFA) appeared in both skeletal and heart muscles. 0.75 IU of insulin kg^–1 b. wt significantly increased the labeled FFA at the 30, 60 and 120 min intervals, with a maximum at 60 min.     

Differential expression of glucose transporters during chick embryogenesis

The patterns of Glut1 and Glut3 glucose transporter protein and mRNA expression were assessed during embryogenesis of chicken brain and skeletal muscle, Glut4 protein levels were also evaluated in skeletal muscle and heart, and Glut1 was examined in the developing heart and liver. Glut1 protein expression was detectable throughout brain ontogeny but was highest during early development. Glut1 mRNA levels in the brain remained very high throughout development. Glut3 protein was highest very early and very late and mRNA was highest during the last half of development. In embryonic skeletal muscle, the levels of Glut1and Glut3 proteins and mRNA were highest very early, and declined severely by mid-development. Glut1 protein and mRNA in the heart also peaked early and then decreased steadily. Although Glut1 mRNA levels were consistently high in the embryonic liver, Glut1 protein expression was not detected. These results suggest that (1) Glut1 is developmentally regulated in chick brain, skeletal muscle, and heart, (2) Glut1 mRNA is present in liver but does not appear to be translated, (3) Glut3 in brain increases developmentally but is virtually absent in muscle, and (4) Glut4 protein and mRNA appear to be absent from chick heart and skeletal muscle. Received 11 January 2001; accepted 14 February 2001     

Potentiation by taurine of the inotropic effect of ouabain and the content of intracellular Ca++ and taurine in the heart

Summary Under certain conditions, taurine (3.0 mM) potentiated cardiac contractile response to ouabain in the normal medium. The potentiation by taurine was also observed in the low K⁺ medium, in which the positive inotropic effect of ouabain increased. The potentiation as seen in both media was, at least in part, due to the increase by taurine of Ca⁺⁺ content in the heart. Taurine in the heart was not directly related to this potentiation.