Typical Time Course Research Articles

Recording the sleep EEG with periorbital skin electrodes

The aim of the study was to examine whether the typical changes of the EEG in the course of a sleep episode can be recorded by skin electrodes placed at the outer canthi of the eyes. In sleep recording from young, healthy subjects, the signals from the electro-oculogram (EOG, El-A2) derivation and a central scalp EEG derivation (C3-A2) were compared. Sleep stage scores obtained separately from each of the two signals yielded highly corresponding values with the exception of stages 2 and 4, for which there were discrepancies. Both signals were subjected to spectral analysis to compare the spectra and their evolution during sleep. An automated detection routine served to identify and eliminate epochs contaminated by eye movement potentials. The typical time course of EEG slow-wave activity (SWA; power density in the 0.75–4.5 Hz range) could be derived from both signals with only minor differences between the data sets. However, compared to the EEG spectra, power density of the EOG spectra was attenuated in frequencies higher than 2 Hz and the typical changes in the spindle frequency range were not evident. The results show that the major sleep parameters as well as the dynamics of SWA can be reliably determined from signals recorded from periorbital skin electrodes.

Effects of partial decortication on opioid analgesia in the formalin test

Partially decorticated rats were tested for their response to nociceptive stimulation in the formalin and tail flick tests, and for the effect of morphine on these responses and on motor activity. Undrugged rats showed vigorous responses to nociceptive stimulation in both tests, and exhibited the typical biphasic time course of pain in the formalin test. Morphine 4 and 8 mg/kg produced dose-dependent analgesia in both tests in sham operated rats, and in rats with lesions that removed all or part of the cortex from the midline to the rhinal fissure (excluding the occipital cortex). In rats with lesions that extended deep into the piriform cortex and damaged the amygdala morphine analgesia was eliminated or attenuated. These and other recent findings suggest that analgesia in the formalin test depends on ascending connections to the forebrain, probably the amygdala.

Dynamics of Slow-Wave Activity and Spindle Frequency Activity in the Human Sleep EEG: Effect of Midazolam and Zopiclone

Electroencephalographic slow-wave activity (SWA; power density in the 0.75 to 4.5 Hz band) and spindle frequency activity (SFA; 11.25 to 15.0 Hz) exhibit a typical time course and a distinct mutual relationship during sleep. Because benzodiazepines (BDZ) suppress SWA and enhance SFA, we investigated the effect of two BDZ-receptor agonists on the dynamics of these EEG parameters. A single dose of midazolam (15 mg), zopiclone (7.5 mg), or placebo was administered before bedtime to healthy young men. Although the two drugs reduced SWA and enhanced SFA, their time course across and within sleep cycles as well as their mutual relationship were little affected. The results constitute further evidence that hypnotics acting as BDZ-receptor agonists do not substantially interfere with the homeostatic aspect of sleep regulation.

A high-field magnetic resonance imaging study of experimental vasogenic brain edema and its response to AVS: 1,2-bis (nicotinamido)-propane.

We clearly represented brain structures of rats and permitted a rapid assessment of water gradient of the brain edema by cortical freezing utilizing a high-field (7T) proton magnetic resonance imaging (MRI). The typical time course of vasogenic edema and the efficacy of AVS; 1,2-bis (nicotinamide)-propane upon the edema were presented. Twelve rats with edema induced by cortical freezing were divided into two groups; one group of animals received 0.5 ml of physiological saline with 100 mg (/kg) AVS every eight hours intraperitoneally. The other group of untreated animals received only saline. One three, six, 12, and 24 hours after lesion production, the profiles of edema fluid spreading and the maximum signal intensity (MI) of some regions of interest (ROI) were assessed by T2 weighted images (TE = 70 ms, TR = 3500 ms). One hour after lesion production in the untreated group, a low heterogeneous intensity area was seen mainly in the primarily injured cortex. Two hours later, the margin of the lesion gradually increased in intensity and MI of ROIs around the lesion also gradually increased. Twenty-four h after lesion production edema extended contralaterally via corpus callosum. AVS reduced edema fluid spreading beginning from about six hours after lesion production. The MIs of the AVS treated group were significantly lower than in the untreated group (p < 0.01). We conclude that sequential observation of edema using MRI is a quite practical technique for evaluation of the efficacy of any therapeutic agent.

Rheological and morphological properties of submerged citric acid fermentation broth in stirred-tank and bubble column reactors

Rheological data for beet molasses broth with Aspergillus niger in pellet form are reported for the biomass developed in a large number of experiments in a 50 l bubble column reactor and a 5 l stirred-tank reactor. The results are summarized in two typical time courses for batch fermentation. Morphological differences caused by the different shear fields in the two reactors are reflected in the rheological differences. The non-Newtonian properties of the whole fermentation broth depend entirely on the concentration and morphology of the biomass since the liquid phase is a low viscosity Newtonian fluid.

Cerebral Hemodynamics in Subarachnoid Hemorrhage Evaluated by Transcranial Doppler Sonography. Part 2. Pulsatility Indices

In previous publications on the diagnostic value of transcranial Doppler sonography (TCD), conflicting results concerning predictive capacities for evaluating vasospasm by measuring flow velocities were reported, and the necessity to examine pulsatility indices (PIs) was stressed. PIs are known to give useful information on cerebral hemodynamics in cases of stenosis of the extracranial internal carotid artery and cerebral arteriovenous malformations. Whether the examination of PIs can give additional information in cases of subarachnoid hemorrhage (SAH) and allow prediction of impending delayed ischemic deficits (DIDs) is still unclear. Normal reference values for the Gosling pulsatility index, the Pourcelot resistance index, and the first Fourier pulsatility index were established in a series of 97 normal subjects. A significant increase in the indices was found as age increased, and there was a strong relation between the indices. There were no statistically significant differences between the right and left sides. An inverse relation was found between the flow velocity and PIs in the middle cerebral artery. In a prospective study of 455 follow-up TCD examinations in 66 SAH patients treated routinely with nimodipine, three different groups were analyzed separately: Group I, patients without DIDs; Group II, patients with DIDs; and Group III, patients with neurological deficits not strictly classifiable as DIDs. The analysis of all three groups together showed a typical time course after the onset of SAH: initially elevated PIs normalized around the tenth day after bleeding. According to Fisher grading, the amount of subarachnoid blood influences the increase in PIs significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial steps of ?and ?-d-glucose binding to intact red cell membrane

The kinetics of the initial phases of D-glucose binding to the glucose transport protein (GLUT1) of the human red cell can be followed by stopped-flow measurements of the time course of tryptophan (trp) fluorescence enhancement. A number of control experiments have shown that the trp fluorescence kinetics are the result of conformational changes in GLUT1. One shows that nontransportable L-glucose has no kinetic response, in contrast to D-glucose kinetics. Other controls show that D-glucose binding is inhibited by cytochalasin B and by extracellular D-maltose. A typical time course for a transportable sugar, such as D-glucose, consists of a zero-time displacement, too fast for us to measure, followed by three rapid reactions whose exponential time courses have rate constants of 0.5-100 sec-1 at 20 degrees C. It is suggested that the zero-time displacement represents the initial bimolecular ligand/GLUT1 association. Exponential 1 appears to be located at, or near, the external membrane face where it is involved in discriminating among the sugars. Exponential 3 is apparently controlled by events at the cytosolic face. Trp kinetics distinguish the Kd of the epimer, D-galactose, from the Kd for D-glucose, with results in agreement with determinations by other methods. Trp kinetics distinguish between the binding of the alpha- and beta-D-glucose anomers. The exponential 1 activation energy of the beta-anomer, 13.6 +/- 1.4 kcal mol-1, is less than that of alpha-D-glucose, 18.4 +/- 0.8 kcal mol-1, and the two Arrhenius lines cross at approximately 23.5 degrees C. The temperature dependence of the kinetic response following alpha-D-glucose binding illustrates the interplay among the exponentials and the increasing dominance of exponential 2 as the temperature increases from 22.3 to 36.6 degrees C. The existence of these interrelations means that previously acceptable approximations in simplified reaction schemes for sugar transport will now have to be justified on a point-to-point basis.

Time profile of calcium accumulation in hippocampus, striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil.

The topical and temporal relationship between neuronal injury and calcium loading was investigated in gerbils following bilateral carotid artery occlusion for 5 or 10 min and recirculation times from 15 min to 7 days. The association of histochemically visible calcium deposits with neuronal death was assessed by combining two calcium stains, alizarin red and arsenazo III, with conventional histological techniques. Neuronal calcium accumulation was evaluated morphometrically in the striatum, the frontoparietal cortex and the CA1 and CA4 sectors of the hippocampus. After 5-min ischemia and 1-2 days of recirculation numerous calcium-containing neurons appeared in the CA4 sector but only a few were present in the CA1 sector. After 4 days of recirculation calcium accumulation was visible in the whole CA1 sector and the dorso-lateral part of striate nucleus. After 10-min ischemia calcium accumulation started in these regions, as well as in the cortex, already after 1 day. In the CA1 sector calcium accumulation followed a typical time course: on day 2 only the lateral parts were affected, while on day 4 the whole CA1 neuronal band was calcium positive. The regional distribution of histological lesions matched that of calcium loading and, furthermore, the lesions appeared after a corresponding delay in the respective regions. Morphometric evaluations of calcium staining and histological lesions in the CA1 sector revealed a high correlation, indicating that calcium accumulation and neuronal death are closely associated both topically and temporally. This suggests that disturbances of calcium homeostasis such as those measured by this histochemical technique are the consequence of and not the reason for ischemic cell death.

Voltage-gated sodium channels expressed in the human cerebellar medulloblastoma cell line TE671

A characterization of the properties of voltage-gated sodium channels expressed in the human cerebellar medulloblastoma cell line TE671 is presented. Membrane currents were recorded under voltage clamp conditions using the patch clamp technique in both the whole-cell and the excised-patch configurations. Macroscopic sodium currents display a typical transient time course with a sigmoidal rise to a peak followed by an exponential decay. The rates of early activation and subsequent inactivation accelerate and approach a maximum in response to test potentials, V, of greater depolarization. The magnitude of peak sodium current increased from negligible values below V = −50 mV and reached a maximum at V = −3.6 mV ± 2.7 mV (mean ± S.E.M., n = 12). Sodium currents reversed at V = + 70 mV, near the predicted Nernst equilibrium potential for a Na + selective channel. The peak sodium conductance, g peak increased with depolarizing voltages to a maximum at V = ∼ 0 mV, exhibiting half-activation voltage at V ≽ −36.8 mV and an e-fold change in g peak/9.5 mV. The Hodgkin-Huxley inactivation parameter h ∞ indicates that at V = −73.6 mV half of the sodium currents were inactivated. Single channel current recordings demonstrated the occurrence of discrete events: the latency for first opening was shorter as the depolarizing pulse became more positive. The single-channel current amplitude was ohmic with a slope conductance, γ = 17.13 pS ± 0.66 pS. Sodium channel currents were reversibly blocked by tetrodotoxin (TTX). Thus, the TE671 human neurons in culture express a sodium channel which exhibits the voltage-gating properties, cation selectivity and neurotoxin sensitivity characteristic of ‘classical’ sodium channels of excitable cells.

Aromatase activity in microsomal preparations of human genital skin fibroblasts: Influence of glucocorticoids

Skin is an important site of estrogen production in men. Although the aromatase complex in these cells appears to be similar to that of other human cells, the regulation of aromatase by glucocorticoids in cultured human skin fibroblasts is unique. We examined aromatase activity in microsomal-enriched fractions of cultured human skin fibroblasts in order to characterize better the factors that regulate the aromatase in these cells. The optimum pH for aromatase activity in microsomal preparations ranged between 7.0 and 7.5. When androstenedione was the substrate, the mean V max was 0.58 pmol/mg protein/h (range: 0.09–1.26 pmol/mg protein/h) and the mean K m was 27 nM (range: 9–50 nM). When aromatase activity was determined as a function of NADPH concentration, the mean V max was 0.39 pmol/mg protein/h (range 0.11–0.82 pmol/mg protein/h) and the mean K m ., was 180 μM (range: 86–300 μM). For skin fibroblasts exposed to DEX, aromatase activity in isolated microsomes and intact cells was stimulated demonstrating a typical time course with peak levels at 14 h and a decline toward baseline with prolonged (48–60 h) exposure. Cytosol from DEX-stimulated cells did not stimulate the aromatase activity in microsomal-enriched preparations from untreated cells. In addition, cytosol from cells incubated with DEX for a prolonged period (60 h) did not inhibit the higher aromatase activity of microsomes from cells incubated with DEX for only 14 h. We previously demonstrated that skin fibroblasts incubated with DEX and CHX produced a superinduction phenomenon for aromatase activity. This superinduction of enzyme activity also occurred in the microsomal-enriched fraction and was unaffected by the cytosol of these cells. These studies exclude the possibility that the unique effects of DEX on the aromatase in human skin fibroblasts are due to the production of either inhibitory or stimulatory soluble factors within cytosol.

Early myocardial lesions in mice with EMC virus myocarditis. Electrocardiographic and morphological findings

Seventy male outbred NMRI mice (6 weeks old) were inoculated with a virus suspension containing 10 p.f.u. of the myocardiotropic variant of EMC virus. Ten mice were killed every other day, electrocardiography and histology were analyzed in a standardized form. ECG recordings at day 0 were used as own controls. We found that the chronological occurrence of ECG abnormalities correlates well with histopathological findings in the acute stage of EMC virus myocarditis. The typical time course in our mouse population was as follows. On day 4 early patchy necrosis was visible, without histological evidence of lymphocytic infiltration. ST displacement was already visible in most cases. Beginning of focal lymphocytic infiltration was seen on day 6 and widespread patchy necroses were observed. Intraventricular conduction defects became more common in addition to AV an SA block on day 8; the first extrasystoles were observed and the QRS voltage started to decrease. Heavy lymphocytic infiltrates occurred on day 10; at this time virtually all animals showed ST displacement. On day 14 infiltrates started to diminish and fibrosis began to appear prominent.

Model of the haemodynamic reactions to intermittent coronary sinus occlusion

Coronary sinus pressure data have been obtained from anaesthetized dogs during pressure controlled intermittent coronary sinus occlusion. It is the main aim of this paper to provide a mathematical procedure for modelling the typical time course of sinus pressure after temporary obstruction of the sinus. The model is produced by fitting a parameterized function to the systolic and diastolic pressures in order to represent mathematically the shape of the curves. The parameters characterize the rise in coronary sinus pressure following occlusion, and are used to calculate ‘derived quantities’ which mimic the physician's visual assessment of trace recordings and their clinical implications in certain forms of coronary sinus pressure reaction. This procedure should be thought of as a kind of pattern recognition which reflects the changing state of the myocardium. The mathematical results are shown to bear a close resemblance to the clinical effects of coronary sinus occlusion.

In vivo measurement of fundus pulsations by laser interferometry

A new noninvasive interferometric technique is described that yields information about the hemodynamic conditions at the fundus. Typical results as obtained from normal subjects are presented and briefly discussed. There is a typical position-dependent time course of the blood pulse induced dilatation of the fundus tissue.

Effect of ocular pigmentation on pilocarpine pharmacology in the rabbit eye. II. Drug response

The time course of the miotic response of pilocarpine in albino and pigmented rabbit eyes was studied after ocular application of 0.11. 0.43, 0.85 and 2.30 mg doses in eye drops and 0.85 and 2.30 mg doses in polymer matrices. When administered in eye drops ocular pigmentation delayed the onset of the peak effect of the 3 smallest pilocarpine doses. The magnitude of the peak effect was lower in pigmented than in albino eyes after 0.11 and 0.43 mg doses, but equal after larger doses. Ocular pigmentation increased the relative biophasic availability of 0.85 and 2.30 mg doses of pilocarpine. This was due to the slower elimination rate of pilocarpine from pigmented tissues. The relative biophasic availability of 0.11 and 0.43 mg doses of pilocarpine was not affected by the ocular pigmentation, because of the opposite effects of lower peak effect and slower elimination rate on biophasic availability in pigmented eyes. The administration of pilocarpine in polymer matrices increased the relative biophasic availability of the drug. When administered in polymer matrices, pilocarpine showed a typical time course of prolonged pulse-entry of the drug into the eye.

Non-linear pressure development during velocity controlled volume releases in isolated contracting rabbit left ventricle

Pressure responses obtained during steady-volume releases performed on isolated contracting rabbit left ventricle reveal a typical non-linear time course, dependent on velocity of volume release (VVR) and on amplitude of volume release (AVR). For values of VVR = 4.8 ml/s and of AVR = 0.28 ml (about 20% of the EDV at preload 0.5 kPa) a shoulder shaped pressure-time course is observed. The shoulder is seen during releases independently of the time during systole at which the release starts. When releases are compared which start at the same time during systole but have different velocities then the shoulder appears at higher amplitudes for the higher velocities. The shoulder can be explained by an active actin-myosin interaction within the scheme of a multi-state contraction model.

Irreversible thermodynamics of an isometric twitch, time-dependent general formulation.

We used the phenomenological laws of irreversible thermodynamics, to derive a system of coupled differential equations describing the time course of the mechanochemical coupling underlying an isometric twitch. Our general description is concerned only with the fundamental process of energy transduction taking place within an idealized unit element of muscle and does not include the description of associated processes such as the excitation-contraction coupling and the mechanical or external coupling that, in bulk muscle, lead to or mediate the fundamental process. The values of the initial conditions and of four parameters are required to solve for the time course of the process. Two of the parameters have a clear physical interpretation and, for the specific case of muscular contraction involving hydrolysis of ATP, their values can be readily estimated from available experimental data. The interpretation of the two other parameters is more speculative, but, from their strong interdependence with the other parameters, their values can be also approximated. Solution of the coupled differential equations yields results consistent with the typical experimental time course of an isometric twitch.

Segmental heterogeneity of epithelial transport in rat large intestine.

Functionally isolated segments of rat colon and rectum were perfused in situ in a closed loop system. Rectum was defined as the lower 25--35% of the length of large intestine (cecum excluded). Perfusion conditions were optimized at 0.5 ml.min-1 and 3 cm H2O luminal pressure. Variation of perfusion rate between 0.2 and 2 ml.min-1 did not influence net volume transport (JNV). Luminal distension following elevation of hydrostatic pressure to 18 cm H2O reversibly increased Jnv. Under control conditions Jnv and Na+-transport rates (JnNa) of colon were 2--3 times higher than those of rectum. In colon transepithelial electrical potential difference (psims) was time independent --12 mV (lumen negative) whereas rectal psims increased with time from --6 mV, reaching a plateau of --67 mV within 6 h. Amiloride 10(-4) mol.l-1 had no effect on psims, Jnv, and JnNa in colon but did slightly depress K+-secretion in colon descendens. In contrast, psims in rectum was dose-dependently depressed, being reversed to +7 mV at 10(-4) mol.l-1. Jnv and JnNa were decreased by half. Acetazolamide in addition to amiloride lowered the positive post-amiloride rectal psims by half. Adrenalectomy had no effect on colonic psims, but abolished psims of the rectum. A single dose of 40 microgram.kg-1 b.w. aldosterone during the experiment restored the typical time course of rectal psims, but did not affect psims in colon. It is concluded that aldosterone induces an amiloride-sensitive Na+-pathway only in rectum, but not in colon, and that colon and rectum differ basically in their transport properties, quantitatively as well as qualitatively, as do the kidney distal convoluted tubule and the cortical collecting duct.

Interferon-mediated inhibition of mouse mammary tumor virus expression in cultured cells

The effect of interferon on glucocorticoid-stimulated mouse mammary tumor virus expression in a murine mammary tumor cell line, Mm5mt/c 1, was investigated. Interferon at a concentration of 10–100 IU/ml causes a 5- to 10-fold inhibition of virus production. The effect has the typical time course of interferon action, is dose dependent and reversible, and is not associated with depression of cellular synthesis of macromolecules. The mechanism appears complex. In contrast to the interferon-mediated inhibition of murine leukemia virus, cellular RNA-dependent DNA polymerase (RDDP) is significantly reduced. The ratio of cellular to extracellular RDDP is, however, increased, and expression of mouse mammary tumor virus antigens on the cell membrane is not inhibited. The evidence therefore suggests effects of interferon on translation or transcription of some viral macromolecules as well as on viral assembly and release.

Creep after loading in the relaxed and contracted smooth muscle (taenia coli of the guinea pig) under various osmotic conditions.

1. Experiments to investigate the creep phenomena of the taenia coli were performed in hypotonic (207 mosm) and hypertonic (447 or 463 mosm) media, in the relaxed (Ca2+-depletion + verapamil) as well as in the contracted (K2SO4-depolarized) state. They were compared with earlier results in isotonic media. The samples were standardized with respect to their volume (weight) before the beginning of the experiment. 2. Neither in the relaxed, nor in the contracted state was there a statistically significant difference in mean total length observed within each test series after loading with 9928 dyn for 2000 s (about 33 min) in the different osmotic media. We define total length as unloaded initial length lo + initial pure leastic extension lE + creep N. 3. In the contracted state the mean total lengths attained by elastic extension and creep are significantly greater than in the relaxed state in both hypotonic and isotonic media. The greater variance in the data for hypertonic solutions makes any statistical decision of this kind impossible. 4. The typical time course of creep (N) and particularly the hyperbolic dependance of N and dN/dt stated in an earlier paper could also be observed here under varied osmotic conditions. 5. The results suggest that the viscosity of the cell plasma is not significant for the time course and extent of creep in smooth muscles of vertebrates. Creep probably takes place in the solid structures of the cells: most particularly the contractile proteins may be involved.

A simple device to measure root growth rates

The construction and use of a simple auxanometer is described. With this instrument students can readily and accurately measure root growth rates of intact seedlings. Typical time course data are presented for the effect of ethylene and indole acetic acid on pea root growth.