Background: Glutamate transporters play an important role in maintaining extracellular glutamate homeostasis. The authors studied the effects of volatile anesthetics on one type of glutamate transporters, excitatory amino acid transporter type 3 (EAAT3), and the role of protein kinase C in mediating these effects.
Methods: Excitatory amino acid transporter type 3 was expressed in Xenopus oocytes by injection of EAAT3 mRNA. Using two-electrode voltage clamp, membrane currents were recorded before, during, and after application of l-glutamate. Responses were quantified by integrating the current trace and are reported as microcoulombs. Data are mean +/- SEM.
Results: l-Glutamate-induced responses were increased gradually with the increased concentrations of isoflurane, a volatile anesthetic. At 0.52 and 0.70 mm isoflurane, the inward current was significantly increased compared with control. Isoflurane (0.70 mm) significantly increased Vmax (maximum velocity) (3.6 +/- 0.4 to 5.1 +/- 0.4 [mu]C;P < 0.05) but not Km (Michoelis-Menten Constant) (55.4 +/- 17.0 vs. 61.7 +/- 13.6 [mu]m;P > 0.05) of EAAT3 for glutamate compared with control. Treatment of the oocytes with phorbol-12-myrisate-13-acetate, a protein kinase C activator, caused a significant increase in transporter current (1.7 +/- 0.2 to 2.5 +/- 0.2 [mu]C;P < 0.05). Responses in the presence of the combination of phorbol-12-myrisate-13-acetate and volatile anesthetics (isoflurane, halothane, or sevoflurane) were not greater than those when volatile anesthetic was present alone. Oocytes pretreated with any of the three protein kinase C inhibitors alone (chelerythrine, staurosporine, or calphostin C) did not affect basal transporter current. Although chelerythrine did not change the anesthetic effects on the activity of EAAT3, staurosporine or calphostin C abolished the anesthetic-induced increase of EAAT3 activity. 相似文献
Plasma creatinine may not reflect glomerular filtration rate (GFR) especially in the early stages of chronic kidney disease (CKD). Plasma cystatin C (cysC), however, has the potential to more accurately determine early GFR reduction. We sought to improve the creatinine-based GFR estimation by including cysC measurements. We derived a reference GFR from standard dual plasma sampling (99m)Tc-DTPA clearance in a training cohort of 376 randomly selected adult Chinese patients with CKD. We compared reference values to estimated GFR and applied multiple regression models to one equation based solely on cysC, and to another combining plasma creatinine (Pcr) and cysC measurements of the training cohort. The results were validated by testing an additional 191 patients. The difference, precision, and accuracy of the two estimates were compared with the modified Modification of Diet in Renal Disease (MDRD) equation for Chinese patients, and another estimate combining cysC and modified MDRD calculations. The estimated GFR combining Pcr and cysC measurements more accurately matched the reference GFR at all stages of CKD than the other equations, particularly in patients with near-normal kidney function. 相似文献
Background: Preconditioning the brain with relatively safe drugs seems to be a viable option to reduce ischemic brain injury. The authors and others have shown that the volatile anesthetic isoflurane can precondition the brain against ischemia. Here, the authors determine whether isoflurane preconditioning improves long-term neurologic outcome after brain ischemia.
Methods: Six-day-old rats were exposed to 1.5% isoflurane for 30 min at 24 h before the brain hypoxia-ischemia that was induced by left common carotid arterial ligation and then exposure to 8% oxygen for 2 h. The neuropathology, motor coordination, and learning and memory functions were assayed 1 month after the brain ischemia. Western analysis was performed to quantify the expression of the heat shock protein 70, Bcl-2, and survivin 24 h after isoflurane exposure.
Results: The mortality was 45% after brain hypoxia-ischemia. Isoflurane preconditioning did not affect this mortality. However, isoflurane preconditioning attenuated ischemia-induced loss of neurons and brain tissues, such as cerebral cortex and hippocampus in the survivors. Isoflurane also improved the motor coordination of rats at 1 month after ischemia. The learning and memory functions as measured by performance of Y-maze and social recognition tasks in the survivors were not affected by the brain hypoxia-ischemia or isoflurane preconditioning. The expression of Bcl-2, a well-known antiapoptotic protein, in the hippocampus is increased after isoflurane exposure. This increase was reduced by the inhibitors of inducible nitric oxide synthase. Inducible nitric oxide synthase inhibition also abolished isoflurane preconditioning-induced neuroprotection. 相似文献
BACKGROUND: The renal dynamic imaging method (modified Gate's method) with (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) is simple and less time consuming for glomerular filtration rate (GFR) estimation than other methods. However, its diagnostic performance as a surrogate marker of GFR is questioned increasingly. Recently, the modified Modification of Diet in Renal Disease (MDRD) study equation based on data from Chinese patients of chronic kidney disease (CKD) showed significant performance improvement. In the present study, the renal dynamic imaging methods and the modified abbreviated MDRD equation were compared with the plasma clearance method. METHODS: Four hundred and eighty two patients with CKD were selected. GFR were estimated simultaneously using three methods: (i) modified Gate's method (gGFR); (ii) the modified abbreviated MDRD equation (c-aGFR) and (iii) dual plasma sampling method (rGFR). Using rGFR as the reference method, gGFR and c-aGFR were compared with rGFR in each stage of CKD. RESULTS: Both gGFR and c-aGFR were correlated well with rGFR (r(gGFR) = 0.81 and r(c-aGFR) = 0.90, P < 0.001). In the overall performance, c-aGFR had less bias (849.5 vs 933.1 arbitrary units), higher precision (57 vs 78.4 ml/min/1.73 m(2)) and higher accuracy than gGFR. For gGFR, the 15, 30 and 50% accuracies were 32.4, 56.0 and 79.1%, respectively; for c-aGFR, the corresponding accuracy rose to 43.2%, 75.5% and 90.9%, respectively. In each stage of CKD, the modified abbreviated MDRD equation also outperformed the modified Gate's method in the GFR estimation. CONCLUSION: Our results indicated that the performance of the renal dynamic imaging in total GFR estimation was not better than the modified abbreviated MDRD equation in our patient group, and should not be used as a surrogate marker of GFR, especially in clinical trials. We presume that the dynamic renal imaging methods for estimation of GFR can be improved by using proper reference GFR, more adequate background subtraction and soft-tissue attenuation correction, in a relatively larger sample size. 相似文献