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We report that preapplication of ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human alpha7 nicotinic acetylcholine receptors reconstituted in Xenopus laevis oocytes and K-28 cells. This potentiation does not result from nonspecific Cl- currents. The concomitant increase in apparent affinity and cooperativity of the dose-response curve suggest that ivermectin acts as a positive allosteric effector. This interpretation is supported by the observation of an increase in efficiency of a partial agonist associated with the potentiation and by the differential effect of ivermectin on mutants within the M2 channel domain. Ivermectin effects reveal a novel allosteric site for pharmacological agents on neuronal alpha7 nicotinic acetylcholine receptors.  相似文献   

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During the last ten years substantial improvement of hardware and software used for the construction of MRI scanners has made available MRI sequences with high temporal and spatial image resolution. Therefore, MR imaging has become an excellent tool and in certain cases the gold standard for the evaluation of cardiovascular diseases. Primary indications for cardiovascular MRI include the assessment of aortic diseases, the arrhythmogenic right ventricle, surgically corrected congenital heart diseases, pericardial disease, intra- and paracardiac tumors and quantification of ventricular function and volumes and myocardial mass. Secondary indications include hypertrophic and dilative cardiomyopathies, valvular and ischemic heart disease. MRI is a totally noninvasive diagnostic technique which is safe and without known harmful potential to biological tissue. The wide diagnostic spectrum providing anatomical, geometrical functional and biochemical information cannot be accomplished by any other diagnostic method.  相似文献   

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The article reviews cardiac magnetic resonance spectroscopy (MRS) in Canada. 31P MRS has been used to study cardiac energetics and intracellular pH in hearts subjected to ischemia-reperfusion and to evaluate the effects of pharmacological interventions. 23Na, 87Rb, and 7Li MRS have provided unique probes to study ion balance and fluxes in intact tissue under normal and stressful physiological conditions. 1H MRS has been used to monitor the accumulation of lactate and lipids in hearts subjected to ischemia-reperfusion and follow the effects of diet on cardiac lipid levels and function. The isolated rat heart has been used most commonly to study the effects of pharmacological agents on energy balance, pH, ion fluxes, and contractile function of the heart subjected to ischemia-reperfusion. The pig heart has been developed as an alternative to the rodent heart because its metabolism is more similar to that of the human heart. Human atrial appendages have been useful in evaluating the effects of preservation strategies (temperature, composition of preservation solutions) on energy levels. The pig heart model has been useful in evaluating the effects of preservation solutions on cardiac function of hearts destined for transplantation. An isolated blood-perfused pig heart model has been developed to assess the effects of cardioplegic strategies on the preservation of contractile function of hearts following surgery on the heart. An in vivo canine model has been used to study myocardial infarction and the effects of therapies to reduce the infarct zones and areas of the heart at risk of infarction. Studies of human hearts in vivo have provided insight into the metabolic adaptations that occur in individuals living at high altitudes.  相似文献   

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Breast MRI is becoming an important tool for the improved management of breast cancer. The technical attributes of high contrast, high-resolution breast MRI acquisitions are summarized. The fundamentals of image interpretation are outlined, including lesion enhancement, morphological features, and extent categories. The indications for breast MRI include compromised mammography, staging of disease within the breast and adjacent structures, difficult histology, and other special diagnostic situations. Patients with compromised mammography include previous surgery, radiographically dense breasts, and silicone augmentation. The improved determination of disease extent aids in the management of breast conservation treatment. Certain lesions, particularly lobular carcinoma and ductal carcinoma in situ, can be better managed with the information available with breast MRI. Other potential indications are also discussed, including patients presenting with positive axillary nodes and no known primary, women with a high risk of malignancy, and recently postoperative breasts with positive margins. The need for MRI stereotaxis is reviewed, with indications and potential solutions. The potential future roles for MRI-directed interstitial hyperthermia are outlined.  相似文献   

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An atypical presentation of a temporal lobe gangliocytoma in an adult female with headaches is reported. Computed tomography showed a hypodense enhancing mass in the right temporal lobe with vasogenic oedema and mass effect. MRI demonstrated a well demarcated mass of low signal on T1W, intermediate signal on PDW, high signal on T2W and homogeneous enhancement on post-gadolinium scan. This case is an addition to the current literature for the characteristic MR features of a ganglion cell tumour.  相似文献   

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A cylindrical 16-pole electromagnet (EM) for electron paramagnetic resonance imaging (EPRI) and low-field magnetic resonance imaging (MRI) has been designed by means of two-dimensional and three-dimensional (3-D) finite element analysis (FEA). The use of an automatic procedure that combines FEA with a minimization routine allowed the optimization of the design, in order to improve the homogeneity along the axis of the EM. A prototype has been built by using electrical steel sheets that were cut by laser; this solution reduced significantly the manufacturing cost. The EM operates with a maximum flux density, in the bore, of 0.08 T and has a homogeneity along the axis of about 40 parts per million (ppm) in a spherical region 10 cm in diameter. It generates the main field and two of the three field gradients required in the 3-D image reconstruction. Good agreement was found between the results of simulation and the measured values.  相似文献   

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Vertebral artery dissection (VAD) is an important cause of posterior circulation stroke in young adults. Initial symptoms are often non-specific and diagnostic arteriography is not performed until neurological deficits are obvious. Since magnetic resonance tomography (MRT) is superior in the diagnosis of vertebrobasilar ischemia, we retrospectively analyzed the role of MRT and MR angiography (MRA) in the detection of dissections of the vertebral artery. Between 1989 and 1995 we identified 24 patients with a vertebral artery dissection and 1 patient with a basilar artery dissection (8 females and 17 males, 23-60 years of age, mean 41.2 years). The diagnosis of VAD (14 left VAD, 9 right VAD, 1 bilateral VAD, 1 basilar artery dissection) was established by specific arteriographical findings (DSA) or clinical and neuroradiological course. All patients underwent a combined MRT/MRA examination protocol at 1.5T that consisted of spin-echo imaging and time of flight MRA of the intra- and extracranial arteries using 2D Flash and 3D Fisp sequences. The MRT/MRA findings were correlated to DSA and ultrasound results. During the acute and subacute stage, MRT/MRA revealed abnormal findings in 21 of 22 dissected vessels (95.5%). There was one false-negative MRT/MRA in a patient with a V1 dissection (intimal flap without peripheral flow disturbances). In 7/22 VAD the MRT/MRA findings were rated specific (double lumen n = 1, mural hematoma n = 4, pseudoaneurysm n = 2). DAS was sensitive in 100% and ultrasound in 77.3%. Specific results were obtained by DSA in 8/ 22 VAD (36.4%) and in 7/22 VAD (30.4%) by MRT/MRA. When MRT/MRA and DSA results were combined, the specific findings increased to 43.5%. Follow-up examinations revealed recanalization in 52% of initially stenosed or occluded vertebral arteries; four patients developed a pseudoaneurysm, and two of them underwent ligation of the VAD. With this retrospective approach, we were able to show a high sensitivity of MRT/ MRA for the presence of disturbed flow in the dissected vertebral artery. The MRA projections tended to overestimate stenosis and were inferior to DSA in the appreciation of irregularities of the vessel wall. Identification of high-grade stenosis, especially in the presence of distal occlusion, was improved on the MRA source images. During the acute and subacute stage, the diagnosis of luminal thrombus can be difficult, because signal ambiguities exist between hemoglobin breakdown products and flow effects and adjacent fat tissues. The differentiation between luminal thrombus and mural hematoma requires interpretation of MRA source images, together with flow compensated spin-echo images. Additional fat suppressed images and flow presaturation may be required at the appropriate levels. The identification of mural hematoma is important, because this finding is considered specific and cannot be obtained with DSA. There is a complementary role of MRT/MRA and DSA for an improved overall specificity for vertebral artery dissection. A negative MRT/MRA result in a patient with appropriate symptoms, however, cannot exclude a dissection and should prompt DSA. On the other hand, a suggestive MRT/MRA result in the appropriate clinical context can replace DSA. The advantage of MRT/MRA is that the method offers a simultaneous diagnosis of posterior fossa ischemia and vertebral artery abnormalities. Therefore, MRT/MRA should be recommended in patients with suspected VAD and especially in those who have no definite neurological deficit. These patients will benefit greatly from early diagnosis and therapy. The fact that all our patients were diagnosed after neurological symptoms and that 64% of them have residual deficits gives an ethical and economical rationale for advocating early MRT/MRA in these patients.  相似文献   

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