知识模式转换在医学科技创新中的作用

医学科技创新是医院赖以生存与发展的动力,医学科技创新的过程也是医学知识模式不断转换的过程,本文从知识模式转换的视角,探讨知识管理对医学科技创新的意义与作用     

Magnetic and electrical stimulation of undulating nerve fibres: a simulation study

Mathematical models of myelinated nerve fibres are highly stylized abstractions of real nerve fibres. For example, nerve fibres are usually assumed to be perfectly straight. Such idealizations can cause discrepancies between theoretical predictions and experimental results. One well-known discrepancy is that the currently used models predict (contradictory to experimental findings) that an activation of nerve fibres is not possible with a pure transverse electric field. This situation occurs when a magnetic coil is placed symmetrically above a straight nerve fibre for magnetic nerve stimulation, or when an anode and a cathode are placed equidistantly on a line perpendicular to the fibre in the case of electrical stimulation. It is shown that this discrepancy does not occur if the physiological undulation of peripheral nerve fibres is included in the models. Even for small undulation amplitudes (e.g. 0.02 mm), it is possible to activate the fibre in these positions. For physiological undulations, as found in the literature, and favourable (off-centre) positions, the typical reduction of the thresholds is in a range between one and five, compared with perfectly straight fibres.     

Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease

Objective　To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). Methods　This model was developed by exposure of rats to 250 ppm SO2 gas, 5?h/d, 5d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. Results　Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038±0.011, pmol/mg protein) and affinity (Kd, 23±11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030±0.008 and 29±19, respectively, P>0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). Conclusion　A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.     

Left-ventricular pressure gradients: a computer-model simulation

Both invasive left-ventricular pressure measurements and non-invasive colour M-mode echographic measurements have shown the existence of intraventricular pressure gradients (IVPGs) during early filling. The mechanisms responsible for these IVPG cannot be completely explained by the experiments. Therefore a one-dimensional numerical model is developed and validated. The model describes filling (both velocities and pressures) along a left ventricular (LV) base-apex axis. Blood-wall interaction in the left ventricle with moving boundaries is taken into account. The computational results for a canine heart indicate that the observed IVPGs during filling are the consequence of a complex interaction between, on the one hand, pressure waves travelling in the LV and, on the other hand, LV geometry, relaxation and compliance. The computational results indicate the pressure dependency of wavespeed (0.77-1.90 m-1 s) for different mean intraventricular pressures (0.88-5.00 mmHg) and IVPGs up to 2 mmHg, independent of the ratio of end systolic volume and equilibrium volume. Increasing relaxation rate not only decreases minimum basal pressure (2.8 instead of 3.6 mmHg) but also has a strong influence on the time delay between the minimum basal and apical pressures (14 ms instead of 49 ms). The results sustain the hypothesis that pressure-wave propagation determines IVPGs and that IVPGs are no proof of elastic recoil.     

Altered mitochondrial oxidative phosphorylation in hippocampal slices of kainate-treated rats

Mitochondria provide the main neuronal energy supply and are important organelles for the sequestration of intracellular Ca2+. This indicates a possible important role for mitochondria in modulating neuronal excitability in normal function as well as in disease. Therefore, we have investigated mitochondrial oxidative phosphorylation in the kainate model of epilepsy. We measured the oxygen consumption of single 400-micron rat hippocampal slices applying high resolution respirometry and determined mitochondrial NAD(P)H autofluorescence signal changes in single slices by laser-excited fluorescence spectroscopy. We observed an about 2-fold higher (p<0.001) basal glucose oxidation rate in slices from kainate-treated animals. This increased endogenous energy consumption was found to be unrelated to spontaneous activity since it was not sensitive to the inhibitors of the sodium-potassium ATPase ouabain and of the mitochondrial adenine nucleotide translocator atractyloside. This finding suggested an increased mitochondrial energy turnover in kainate-induced epilepsy. Furthermore, the uncoupler-stimulated oxygen consumption of the slices was approximately 1.3-fold higher (p<0.01) in the kainate model. In accordance with the respirometric data, fluorescence spectroscopy showed decreased reduction levels of the mitochondrial NAD-system in glucose oxidizing slices from kainate-treated rats. The preincubation of epileptic hippocampal slices with either BAPTA AM, ruthenium red or TPP+ increased the atractyloside sensitivity of glucose oxidation to about 1.4-fold (p<0.01). These observations indicate that the increased mitochondrial energy turnover in hippocampal slices from kainate-treated rats is most possibly caused by futile Ca2+-cycling.     

Inositol reduces depressive-like behaviors in two different animal models of depression

  Rationale: Myo-inositol is an isomer of glucose that is a precursor in the phosphatidylinositol (PIP) cycle, a source of two second messengers: diacylglycerol (DAG) and inositol triphosphate (IP₃). Clinical studies have reported that inositol is effective in relieving symptoms of depression. Objective: The present study examined the effects of inositol on two animal models of depression: the Porsolt forced swim test, a behaviorally based model; and the reserpine-induced immobility model, a pharmacologically based model. Methods and results: Chronic inositol injections (daily for 14 days) of 1.2 g/kg (but not at lower doses) reduced immobility time and increased struggle time in the Porsolt test compared with control animals. The same dose and treatment schedule also reduced complete immobility time but did not affect ambulatory activity in the reserpine test compared with controls. Chronic oral treatment with inositol (10% in food for 14 days) had effects similar to IP inositol in the Porsolt test. Conclusions: The effect of inositol in animal models of depression supports its possible importance as a new treatment for the disorder, and permits research on its mechanisms of action. Received: 31 August 1998 / Final version: 18 November 1998     

The effect of separate red blood cells on capillary tissue oxygenation calculated with a numerical model

Author to whom correspondence should be addressed In simplified models that describe large quantities of capillariesthe capillary content is considered to be homogeneous for oxygentransport; but, in reality, the capillaries contain discretered blood cells (RBCs), and this discreteness will affect oxygentransport from the capillary to the tissue. This was previouslyinvestigated with an analytical model, where RBCs were modelledas point-like sources. A numerical approach is used in thisinvestigation, and the results are compared with the analyticalmodel. In both models the effect of the particulate nature ofblood depends on the haematocrit and on the RBC velocity. Thereis only a minor difference between the two models. For rat hearts,the correction factor used in this study, the extraction pressure,can be up to 3 kPa (23 mmHg).