Intrinsic properties and extrinsic neurohormonal control of crab cardiac hemodynamics

This report provides the first direct measurements of the stroke volume and total cardiac output of crustacean hearts, as recorded from a semi-isolated in vitro preparation. The responses to mechanical perturbations, changes in preload and afterload, show that these hearts do not possess automatic compensatory Frank-Starling-like mechanisms. Heart rate, reflecting the burst rate of the cardiac ganglion, is minimally affected by stretch. On the other hand, these hearts are exquisitely responsive to the neurohormones of the pericardial organs. Serotonin, CCAP and proctolin all produce positive chronotropic and inotropic effects, but the responses to each are unique. Two FMRFamide peptides were positively chronotropic, but negatively inotropic.     

Postnatal development of adrenergic and cholinergic sensitivity in the isolated rat atria

The sensitivity to adrenergic drugs in isolated rat atria increased with the postnatal development. The cholinergic chronotropic sensitivity did not further change after birth.     

Postnatal development of adrenergic and cholinergic sensitivity in the isolated rat atria

Summary The sensitivity to adrenergic drugs in isolated rat atria increased with the postnatal development. The cholinergic chronotropic sensitivity did not further change after birth.     

Quantitative changes in β-adrenergic responses of isolated atria from hyper- and hypothyroid rats

Summary Concentration-response curves for the chronotropic and inotropic effects of isoprenaline, in the absence and presence of propranolol, were obtained on heart atria isolated from normo- or dysthyroid rats. Hyperthyroidism increased the chronotropic potency and efficacy of the -adrenergic agonist. The results are compatible with the view that thyroid hormone increases the density of functional -adrenoceptors in cardiac pacemaker tissue.This study was supported by the Swiss National Science Foundation grant No. 3.374.-0.78. We thank Dr Bachmann from the Central Laboratory of the University Hospital Bern for the estimation of plasma thyroxine levels.     

An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools

Urethane (1 X 10(-2) - 1 X 10(-1) M) reduced, in a concentration-dependent manner, both intra and extracellular Ca++ dependent noradrenaline-induced contractions of perfused rabbit ear artery as well as the tonic contractions produced by perfusion with high K+ solution. However, a quantitative analysis of the data indicated that for urethane concentrations similar to those found in plasma during anesthesia urethane antagonism is confined to noradrenaline-induced contractions which depend upon the mobilization of Ca++ from intracellular storage sites. In KCl-contracted arteries, urethane enhanced the relaxant effects of isoprenaline. - Urethane reduced the amplitude of contractions of spontaneously beating guinea-pig right atrium at concentrations which have only a limited effect on frequency. In addition, it decreased in a concentration-dependent manner the amplitude of isoprenaline-activated electrically driven, and K+ depolarized guinea-pig right ventricular strips. Urethane had no effect on the chrono and inotropic actions of isoprenaline on cardiac preparations. In in vivo experiments the chronotropic response to low doses of isoprenaline was significantly higher in urethane-treated as compared to unanesthetized rats. The higher dose of isoprenaline tested produced a significant fall in systolic blood pressure in urethane-anesthetized rats. A significant correlation exists between the chronotropic response to isoprenaline and resting heart rate values in urethane-anesthetized rats. These results indicate that urethane, at concentrations similar to those found in plasma during anesthesia selectively interferes with mobilization of Ca++ from intracellular storage sites. In addition, the interference of urethane anesthesia with the isoprenaline chronotropic effect 'in vivo' cannot be explained by a direct interference of urethane with beta-adrenoceptors at cardiac level.     

Chronic exercise does not alter the chronotropic response of isolated rat atria to catecholamines

Summary Atria isolated from rats after 7 weeks of exercise training beat at a slower rate than did atria from sedentary controls. There is no significant difference between the chronotropic responses of the 2 groups to epinephrine or morepinephrine.This study was supported in part by a grant from the Genesee Valley Heart Association.     

Alpha-receptor subsensitivity of isolated atria from rats following repeated injections of phenylephrine or isoprenaline

Summary Daily injections of phenylephrine or isoprenaline for 4 or 7 days lowered the chronotropic sensitivity of -adrenoreceptors in isolated rat atria.This study was supported by grants from the National Science Council of Finland.     

An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools

Summary Urethane (1×10^–2–1×10^–1 M) reduced, in a concentration-dependent manner, both intra and extracellular Ca⁺⁺ dependent noradrenaline-induced contractions of perfused rabbit ear artery as well as the tonic contractions produced by perfusion with high K⁺ solution. However, a quantitative analysis of the data indicated that for urethane concentrations similar to those found in plasma during anesthesia urethane antagonism is confined to noradrenaline-induced contractions which depend upon the mobilization of Ca⁺⁺ from intracellular storage sites. In KCl-contracted arteries, urethane enhanced the relaxant effects of isoprenaline.—Urethane reduced the amplitude of contractions of spontaneously beating guinea-pig right atrium at concentrations which have only a limited effect on frequency. In addition, it decreased in a concentration-dependent manner the amplitude of isoprenaline-activated electrically driven, and K⁺ depolarized guinea-pig right ventricular strips. Urethane had no effect on the chrono and inotropic actions of isoprenaline on cardiac preparations. In in vivo experiments the chronotropic response to low doses of isoprenaline was significantly higher in urethane-treated as compared to unanesthetized rats. The higher dose of isoprenaline tested produced a significant fall in systolic blood pressure in urethane-anesthetized rats. A significant correlation exists between the chronotropic response to isoprenaline and resting heart rate values in urethane-anesthetized rats. These results indicate that urethane, at concentrations similar to those found in plasma during anesthesia selectively interferes with mobilization of Ca⁺⁺ from intracellular storage sites. In addition, the interference of urethane anesthesia with the isoprenaline chronotropic effect in vivo cannot be explained by a direct interference of urethane with -adrenoceptors at cardiac level.     

Reduction of isoprenaline induced tachycardia in pregnant rats. Role of a serum factor]

The in vivo isoprenaline (50 microgram/kg) induced tachycardia (beta 1 adrenergic stimulant effect) was decreased in pregnant (20th day) Rats compared to non pregnant Rats. The in vitro positive chronotropic effect of isoprenaline (10 ng/ml) on cultured Rat heart cells was abolished by pregnant Rat serum whereas progesterone (0.10 to 5 microgram/ml) or oestradiol (0.1 to 25 microgram/ml) were ineffective. The decreased beta 1 adrenergic responsiveness in pregnant Rats could be related to a seric factor, different from these two hormones.     

Der Einfluß von Desoxycorticosteron auf die Azetylcholinwirkung am isolierten Froschherz

Summary The action of desoxycorticosteronglucoside was tested on the isolated frog-heart. In concentrations of 10^–6 to 10^–4 a small negative inotropic effect is prevailing. Acting together with acetylcholine, the substance diminishes or abolishes the negative inotropic and chronotropic action of acetylcholine. Eserin has no influence and the inhibition is also observed with cholinchloride and the carbaminoyl ester of choline. This inhibitory action bears a close resemblance to the inhibitory action of thiamin. In both cases a complex mechanism seems to be involved.     

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.     

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.     

Cephalopod myocardial receptors: Pharmacological studies on the isolated heart ofSepia officinalis (L.)

Summary This paper presents a synopsis of the information available about the pharmacological action of various substances on the cephalopod heart, with special emphasis on the central heart ofSepia officinalis. Threshold concentrations, EC₅₀ values and maximum effective concentrations have been experimentally determined. Studies with various transmitter substances, analogous compounds and antagonists have led to the following picture: Acetylcholine is the natural inhibitory transmitter substance; it acts via receptors with nicotinic properties which can be blocked by d-tubocurarine and -bungarotoxin. The probable excitatory transmitter system is represented by a noradrenergic innervation. Noradrenaline has a positive inotropic and a positive chronotropic action on in vitro heart preparations. A positive inotropic response can also be evoked by serotonin (5-HT); this effect is not due to stimulation of the catecholamine receptor, as is shown by cross-over experiments with specific blocking agents. Furthermore, a peptidergic receptor system has been described which reacts with the molluscan cardioactive peptide FMRF amide most effectively. It is assumed that cardioactive peptides may reach the central heart in the circulating blood; the sites of synthesis and release are still unknown. Possibly the NSV-layer of the vena cava is involved in hormonal cardiovascular regulation processes.     

The emerging roles for the chromatin structure regulators CTCF and cohesin in neurodevelopment and behavior

Recent genetic and technological advances have determined a role for chromatin structure in neurodevelopment. In particular, compounding evidence has established roles for CTCF and cohesin, two elements that are central in the establishment of chromatin structure, in proper neurodevelopment and in regulation of behavior. Genetic aberrations in CTCF, and in subunits of the cohesin complex, have been associated with neurodevelopmental disorders in human genetic studies, and subsequent animal studies have established definitive, although sometime opposing roles, for these factors in neurodevelopment and behavior. Considering the centrality of these factors in cellular processes in general, the mechanisms through which dysregulation of CTCF and cohesin leads specifically to neurological phenotypes is intriguing, although poorly understood. The connection between CTCF, cohesin, chromatin structure, and behavior is likely to be one of the next frontiers in our understanding of the development of behavior in general, and neurodevelopmental disorders in particular.     

高校产学研一体化发展的实践与前瞻

本文探讨我国高校产学研一体化发展的必要性、可行性及其前景。从人类社会发展的历史特点入手，并借鉴了美国硅谷发展的经验和我国改革开放推进社会主义市场发展的需求，对高校产学研一体化发展的道路作了论述。针对目前高校产学研一体化中存在的问题，作者提出了加速高校产学研一体化发展的四条建议：1，高校产学研一体化发展必须转变观念，积极参与社会大循环；2，推进高校产学研一体化要有过硬的产品和准确的市场定位；3，高校产学研一体化发展要依托高科技园区，切实解决经费投入问题；4，高校产学研一体化发展要突出以人为本的思想，努力造就发明家和企业家。     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early, in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocytemacrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of houng adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed, and/or were first to recover, even during continued drug exposure.     

Developmental and ageing changes in aminopeptidase activities in selected tissues of the rat

Aminopeptidase activities, assayed as arylamidase activities, were investigated in selected tissues of 1, 6, 12 and 24-month-old rats. The enzyme activities were found to have a heterogeneous distribution and age-related changes were observed. The highest levels of soluble arginyl-aminopeptidase activity were detected in brain homogenate at all the studied ages, whereas membrane-bound activity presented the highest levels in brain and kidney in the four ages tested. Aspartyl-aminopeptidase activity was detected mainly in the particulate fraction of kidney at all four ages. In 1, 6 and 12-month-old animals, soluble aspartyl-aminopeptidase activity was also higher in the kidney than in the rest of the tissues, whereas in the group of 2-year-old rats, the highest levels were found in both kidney and liver. Age-related changes were observed in all the studied tissues and for all the assayed enzymatic activities. In general, the maximal levels were detected in both the youngest and the oldest animals, and the minimal ones in 6 and 12-month-old rats. However, in the adrenals, the soluble and membrane-bound arginyl-aminopeptidase activity was higher in 6-month and 2-year-old rats than in 1-month and 12-month-old rats. These changes may reflect the functional status of the susceptible endogenous substrates of aminopeptidases.     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice.

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocyte-macrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of young adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed and/or were first to recover, even during continued drug exposure.     

Effects of Freund's complete adjuvant on the dirunal rhythms of neuroendocrine processes and ornithine decarboxylase activity in various tissues of male rats

The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.     

Schwann cell mitochondria as key regulators in the development and maintenance of peripheral nerve axons

Formation of myelin sheaths by Schwann cells (SCs) enables rapid and efficient transmission of action potentials in peripheral axons, and disruption of myelination results in disorders that involve decreased sensory and motor functions. Given that construction of SC myelin requires high levels of lipid and protein synthesis, mitochondria, which are pivotal in cellular metabolism, may be potential regulators of the formation and maintenance of SC myelin. Supporting this notion, abnormal mitochondria are found in SCs of neuropathic peripheral nerves in both human patients and the relevant animal models. However, evidence for the importance of SC mitochondria in myelination has been limited, until recently. Several studies have recently used genetic approaches that allow SC-specific ablation of mitochondrial metabolic activity in living animals to show the critical roles of SC mitochondria in the development and maintenance of peripheral nerve axons. Here, we review current knowledge about the involvement of SC mitochondria in the formation and dysfunction of myelinated axons in the peripheral nervous system.