Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. (57/2604)

The diffraction barrier responsible for a finite focal spot size and limited resolution in far-field fluorescence microscopy has been fundamentally broken. This is accomplished by quenching excited organic molecules at the rim of the focal spot through stimulated emission. Along the optic axis, the spot size was reduced by up to 6 times beyond the diffraction barrier. The simultaneous 2-fold improvement in the radial direction rendered a nearly spherical fluorescence spot with a diameter of 90-110 nm. The spot volume of down to 0.67 attoliters is 18 times smaller than that of confocal microscopy, thus making our results also relevant to three-dimensional photochemistry and single molecule spectroscopy. Images of live cells reveal greater details.  (+info)

Modeling of blood flow as the result of filtration-reabsorption processes in capillaries. (58/2604)

In our previous article (Am J Physiol Adv Physiol Educ 272: S26-S30, 1997) we proposed a model that permits analysis for the change of hemodynamics in vessels with local stenosis. This problem is connected with the blood-tissue metabolism. This article continues the classroom research on concepts related to blood flow physiology. We take into consideration the problem of the blood-tissue fluid exchange. A model based on basic principles of hydrodynamics and mathematics is proposed for analysis of "filtration-reabsorption equilibrium" and its disturbances under different external influences. It permits medical students to develop a scientific analytic approach to the solution of physiological and pathophysiological hemodynamics problems.  (+info)

Effects of collagenase and elastase on the mechanical properties of lung tissue strips. (59/2604)

The dynamic stiffness (H), damping coefficient (G), and harmonic distortion (k(d)) characterizing tissue nonlinearity of lung parenchymal strips from guinea pigs were assessed before and after treatment with elastase or collagenase between 0.1 and 3.74 Hz. After digestion, data were obtained both at the same mean length and at the same mean force of the strip as before digestion. At the same mean length, G and H decreased by approximately 33% after elastase and by approximately 47% after collagenase treatment. At the same mean force, G and H increased by approximately 7% after elastase and by approximately 25% after collagenase treatment. The k(d) increased more after collagenase (40%) than after elastase (20%) treatment. These findings suggest that, after digestion, the fraction of intact fibers decreases, which, at the same mean length, leads to a decrease in moduli. At the same mean force, collagen fibers operate at a higher portion of their stress-strain curve, which results in an increase in moduli. Also, G and H were coupled so that hysteresivity (G/H) did not change after treatments. However, k(d) was decoupled from elasticity and was sensitive to stretching of collagen, which may be of value in detecting structural alterations in the connective tissue of the lung.  (+info)

Kinetic study of acamprosate absorption in rat small intestine. (60/2604)

Acamprosate (calcium bis acetyl-homotaurine), a homotaurine derivative, a structural analogue of gamma-aminobutyric acid (GABA) and an upper homologue of taurine, is a relatively new drug used to prevent relapse in weaned alcoholics. When administered orally as enteric-coated tablets at relatively high doses, this drug has a bioavailability of about 11%; however, the intestinal absorption mechanism has not been studied in depth. The present study was therefore planned to characterize the intestinal transport of acamprosate in the rat and the effect of chronic alcohol treatment on this process, quantifying its kinetic parameters and investigating possible inhibitors. Using an in vitro technique, acamprosate absorption was measured in the rat intestine from three different groups: alcohol group [fed a liquid diet containing 5% (w/v) ethanol for 4 weeks], isocaloric pair-fed control, and a solid diet group. Intestinal acamprosate absorption was found to occur mainly by passive diffusion with a diffusive permeability of 0.213+/-0.004 cm/h in control pair-fed animals, 0.206+/-0.001 cm/h in animals receiving chronic alcohol treatment, and 0.193+/-0.001 cm/h in the solid diet group. Inhibition studies showed that at a 10(-3) M acamprosate concentration, some compounds such as GABA, taurine, proline, and glycine at 40 mM each did not affect acamprosate transport. Nevertheless, when a lower concentration of the drug (10(-4) M) was assayed, a significant reduction of acamprosate transport in the presence of taurine or GABA 40 mM was found. These results suggest that acamprosate in the rat jejunum, could be transported, in part, by a carrier system. Further experiments using different concentrations of taurine (10, 20, and 80 mM) showed that the maximum inhibition (32%) is achieved at 20 mM of taurine. These latter results suggest that acamprosate and taurine share, at least, an intestinal carrier system in rat jejunum. From the above results, it can be concluded that there are probably two pathways involved in the intestinal absorption of acamprosate: passive diffusion and mediated transport, with the former being predominant. Moreover, neither chronic ethanol intake nor the type of diet seems to alter the intestinal absorption of the drug.  (+info)

Deterministic brain oscillations in the magnetoencephalogram. (61/2604)

Determinism is a special property of some systems and is defined by its state-space behavior in which the trajectories in time never intersect. Whether or not determinism exists in brain activities is a question that may be resolved by analysis of the dynamical properties of the electroencephalogram (EEG) or magnetoencephalogram (MEG). We will show that even though there are strong nonstationarities in most brain behaviors, small epochs of deterministic dynamics can still be observed. We will also show that the local Lyapunov exponents are measures that can demonstrate smooth transitions into these deterministic states.  (+info)

Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children. (62/2604)

AIMS: This analysis was performed to validate a previously developed population pharmacokinetic model for lamotrigine in order to establish a basis for dosage recommendations for children. METHODS: (a) The importance of the covariates in the final model was confirmed using the model validation dataset. Population and individual (Bayesian estimate) pharmacokinetic parameters were estimated using both the initial model, which included none of the covariates, and the final model. Accuracy and precision of parameter estimation and of concentration prediction were compared between the two models. (b) The performance in predicting the validation concentrations by the final model parameters obtained previously from the model development dataset was assessed. (c) The parameters of the final model were refined using a dataset combining both the development and validation data. RESULTS: Prediction performance of the final pharmacostatistical model was superior to that of the initial model. The results of the validation confirmed that concomitant antiepileptic drugs that increased or reduced lamotrigine clearance in adults had similar effects in children. The validation also verified the linear relationship between weight and clearance. The previously seen small sex effect on clearance was found statistically insignificant. CONCLUSIONS: The current analysis confirmed the previous findings. To achieve the same concentrations, children receiving enzyme-inducing antiepileptic drugs without valproate require higher doses than those receiving valproate; and heavier children require higher doses.  (+info)

Responses to continuously changing optic flow in area MST. (63/2604)

We studied the temporal behavior and tuning properties of medial superior temporal (MST) neurons in response to constant flow-field stimulation and continuously changing flow-field stimulation (transitions), which were obtained by morphing one flow field into another. During transitions, the flow fields resembled the motion pattern seen by an observer during changing ego-motion. Our aim was to explore the behavior of MST cells in response to changes in the flow-field pattern and to establish whether the responses of MST cells are temporally independent or if they are affected by contextual information from preceding stimulation. We first tested whether the responses obtained during transitions were linear with respect to the two stimuli defining the transition. In over half of the transitions, the cell response was nonlinear: the response during the transition could not be predicted by the linear interpolation between the stimulus before and after the transition. Nonlinearities in the responses could arise from a dependence on temporal context or from nonlinearities in the tuning to flow-field patterns. To distinguish between these two hypotheses, we fit the responses during transitions and during continuous stimuli to the predictions of a temporally independent model (temporal-independence test) and we compared the responses during transitions to the responses elicited by inverse transitions (temporal-symmetry test). The effect of temporal context was significant in only 7.2% and 5.5% of cells in the temporal-independence test and in the temporal-symmetry test, respectively. Most of the nonlinearities in the cell responses could be accounted for by nonlinearities in the tuning to flow-field stimuli (i.e., the responses to a restricted set of flow fields did not predict the responses to other flow fields). Tuning nonlinearities indicate that a complete characterization of the tuning properties of MST neurons cannot be obtained by testing only a small number of flow fields. Because the cells' responses do not depend on temporal context, continuously changing stimulation can be used to characterize the receptive field properties of cells more efficiently than constant stimulation. Temporal independence in the responses to transitions indicates that MST cells do not code for second-order temporal properties of flow-field stimuli, i.e., for changes in the flow field through time that can be construed as paths through the environment. Information about ego-motion three-dimensional paths through the environment may either be processed at the population level in MST or in other cortical areas.  (+info)

Chaotic behavior of renal sympathetic nerve activity: effect of baroreceptor denervation and cardiac failure. (64/2604)

Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in conscious rats subjected to either complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation) or induction of congestive heart failure (CHF). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In control rats, this yielded a system whose correlation dimension converged to a low value over the embedding dimension range of 10-15 and whose greatest Lyapunov exponent was positive. Complete baroreceptor denervation was associated with a decrease in the correlation dimension of the system (before 2.65 +/- 0.27, after 1.64 +/- 0.17; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.201 +/- 0.008 bits/data point before, 0.177 +/- 0.004 bits/data point after, P < 0.02). CHF, a state characterized by impaired sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, was associated with a similar decrease in the correlation dimension (control 3.41 +/- 0.23, CHF 2.62 +/- 0.26; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.205 +/- 0.048 bits/data point control, 0.136 +/- 0.033 bits/data point CHF, P < 0.02). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, occurring either physiologically or pathophysiologically, is associated with a decrease in the correlation dimensions of the system and a reduction in chaotic behavior.  (+info)