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31.
The present study was designed to elucidate whether cephaloridine-induced lipid peroxidation is inhibited by probenecid, cobalt chloride and antioxidants such as alpha-tocopherol and N,N'-diphenyl-p-phenylenediamine (DPPD). Kidney slices obtained from the renal cortex of male Wistar rats were incubated for 1 h in a cephaloridine or cefotaxime (1.25-10 mg/ml) containing medium. In another series of experiments, kidney slices were incubated with cephaloridine or cefotaxime (5 mg/ml) for different periods of time (30-120 min). Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA). Subsequently, kidney slices were incubated in both series of experiments, in a cephalosporin free medium containing tetraethylammonium (TEA). Accumulation of TEA in renal cortical slices, expressed as slice to medium ratio (S/M), was used to measure changes in the transport capacity of the kidney cells. While cefotaxime had only a slight effect, cephaloridine induced a significant time- and concentration-dependent increase of MDA production and a significant time- and concentration-dependent decrease of TEA accumulation. Inhibition of the renal uptake of cephaloridine by probenecid induced a decrease in MDA production and complete recovery of TEA accumulation. The antioxidants DPPD and alpha-tocopherol inhibited cephaloridine-induced lipid peroxidation in a concentration-dependent manner. Recovery of TEA accumulation accompanied the decrease in lipid peroxidation. DPPD was a more potent inhibitor of lipid peroxidation than alpha-tocopherol. Cobalt chloride, known for its ability to decrease cellular concentration of cytochrome P-450, effectively decreased cephaloridine-induced lipid peroxidation. Thus, these findings support the concept that lipid peroxidation has an important role in the development of cephaloridine-induced nephrotoxicity. 相似文献
32.
J. Bargas E. Galarraga J. Aceves 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1988,72(2):390-398
Summary In order to assess the effects of [KK]o on the passive membrane properties of neostriatal neurons, the cable properties of these cells were determined at two extracellular potassium concentrations (6.25 and 3.0 mM). The effect of tetraethylammonium (TEA) on cable properties was also studied at 6.25 [KK]o. At 6.25 mM [KK]o, the mean input resistance at the resting membrane potential (RMP), and the mean membrane time constant (o) were 27±1.5 M and 6.9±0.5 ms respectively (n=17), while at 3 mM [KK]o they were 62.9±4.8 M and 14.3±0.6 ms (n=15) (mean ±SEM). With one of the methods used to calculate the electronic parameters, the total electrotonic length of the dendrites (L) and the dendritic to somatic conductance ratio () were 1.3±0.05 and 5±0.8 at the higher [KK]o respectively, while they were 0.95±0.04 and 3±0.7 at the lower [KK]o. Cells were depolarized in 6.25 as compared to 3 mM [KK]o (RMP=-66±1.3 mV vs RMP=-80.5±1.4 mV). After one hour exposure to TEA (10 mM), the input resistance and time constant tripled at 6.25 mM [KK]o. TEA slightly depolarized the cells bathed in 6.25 mM [KK]o. The results suggest that changes in [KK]o, within the physiological range, markedly affect the cable properties of neostriatal neurons, possibly modifying subthreshold, voltage-dependent KK-conductances. TEA seems to block some of these channels. 相似文献
33.
目的 研究全麻(general anesthesia,GA)复合胸段硬膜外阻滞(thoracic epidural anesthesia,TEA)对术中输注氨基酸患者氧耗量(oxygen consumption,VO2)的影响。方法 选择30例ASAⅠ~Ⅱ级、择期行中上腹部手术的患者,随机分为单纯全麻组(GA组,n=15)和全麻复合TEA组(GAE组,n=15)。入室后行胸段硬膜外穿刺置管、颈内静脉及桡动脉穿刺置管,诱导气管插管后采用Drger Zeus麻醉工作站行Auto control模式机械通气并监测实时VO2,术中七氟醚最低流量紧闭麻醉复合异丙酚、瑞芬太尼输注,根据手术需要间断追加罗库溴铵和芬太尼。两组诱导同时输注18氨基酸注射液4 kJ·kg-1·h-1,持续2 h或手术结束时(手术未满2 h)。GAE组在切皮前分3次给予0.375%布比卡因共10 mL作为负荷量,此后追加4 mL/h,直至手术结束。GA组在相同时间点给予等容积的生理盐水。记录气管插管前5(-5) min和插管后0、5、15、30、45、60、75 min的平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)值和插管后5、15、30、45、60、75 min的VO2和鼻咽温度(Tcore)值。记录术中麻醉药和升压药用量情况。结果 随着输注时间延长,两组VO2均稍上升但差异无统计学意义(P>0.05),且GAE组稍高于GA组,但组间差异无统计学意义(P>0.05);气管插管后30 min后,两组Tcore显著下降并趋于稳定(P<0.05),但组间差异无统计学意义(P>0.05);与GA组相比,GAE组的芬太尼用量(P<0.01)和瑞芬太尼用量(P<0.01)更少,但去氧肾上腺素用量(P<0.01)和麻黄碱用量(P<0.05)更多。结论 与单纯GA相比,GA复合TEA尽管能显著减少患者术中输注氨基酸患者的芬太尼和瑞芬太尼的用量,但并不能降低其VO2。 相似文献
34.
35.
36.
The influence of TTX,DNP and TEA on membrane flicker noise and shot effect noise of the frog node of Ranvier 总被引:1,自引:0,他引:1
E. Siebenga J. de Goede A. A. Verveen 《Pflügers Archiv : European journal of physiology》1974,351(1):25-34
Summary Voltage noise spectra of the node of Ranvier upon depolarization were investigated in normal Ringer solution and in TTX, DNP, TEA and saccharose Ringer. The intensities of both the 1/f component and the shot effect component of the voltage noise did change in TEA Ringer only. This excludes the sodium channels and active transport as sources of these noises. From considerations of a representation of the potassium and leakage system it follows that leakage as the sole noise source is excluded. The shot effect noise is probably caused by fluctuations of the potassium conductance. For the 1/f noise the behaviour is more complex. Part of it however is due to the potassium system.This work was supported by a grant from the Netherlands Organization for Pure Research (Z.W.O.) 相似文献
37.
Rod photoreceptors express a unique type of noninactivating potassium channels, Kx channels, which play an important role in setting the dark potential and participate in shaping the light response. Biophysical studies of Kx channels are limited. For example, the effects of a conventional blocker of potassium channels, tetraethylammonium (TEA), on Kx channels have not been extensively studied. Here we demonstrate that TEA blocks Kx channels, one molecule of TEA being sufficient to block the channel. Half of the Kx current was inhibited at K0.5 = 5.6 mM. The TEA-induced block of Kx channels depended on extracellular potassium: the higher the potassium concentration, the stronger the block. Using TEA, we blocked potassium channels to reveal their role in shaping the simulated light response (SLR) of rods. We showed that TEA slowed down SLR and sometimes caused generation of action potentials. We developed a complete computer model of the rod, which accurately reproduced the main features of the light response and allowed us to demonstrate that it was suppression of Kx channels that was essential for slowing SLR and increasing excitability of rods. The results reported in this work further establish the importance of Kx channels in rod photoreceptor function. 相似文献
38.
Synthesis of an analog of facteur thymique serique (FTS) containing a glutaminyl residue in position 1 of the peptide chain is described. Like the original FTS, Gln1-FTS is able to induce T cell markers on lymphocytes in vitro in a picogram dosage range. The human E-rosette bioassay was adopted for the evaluation of biological activity of Gln1-FTS. It was also shown that the latter method can be used to evaluate the presence of target cells for FTS activity in peripheral blood lymphocytes in humans. 相似文献
39.
M. De Biasi H. A. Hartmann J. A. Drewe M. Taglialatela A. M. Brown G. E. Kirsch 《Pflügers Archiv : European journal of physiology》1993,422(4):354-363
An N-terminus peptide or a C-terminus mechanism involving a single residue in transmembrane segment 6 produces inactivation in voltage-dependent K+ channels. Here we show that a single position in the pore of K+ channels can produce inactivation having characteristics distinct from either N- or C-type inactivation. In a chimeric K+ channel (CHM), the point reversion CHM V 369I produced fast inactivation and CHM V 369S had the additional effect of halving K+ conductance consistent with a position in the pore. The result was not restricted to CHM; mutating position 369 in the naturally occurring channel Kv2.1 also produced fast inactivation. Like N- and C-types of inactivation, pore or P-type inactivation was characterized by short bursts terminated by rapid entry into the inactivated state. Unlike C-type inactivation, in which external tetraethylammonium (TEA) produced a simple blockade that slowed inactivation and reduced currents, in P-type inactivation external TEA increased currents. Unlike N-type inactivation, internal TEA produced a simple reduction in current and K+ occupancy of the pore had no effect. External TEA was not the only cation to increase current; external K+ enhanced channel availability and recovery from inactivation. Additional features of P-type inactivation were residue-specific effects on the extent of inactivation and removal of inactivation by a point reversion at position 374, which also regulates conductance. The demonstration of P-type inactivation indicates that pore residues in K+ channels may be part of the inactivation gating machinery. 相似文献
40.
Vectorial secretion of cationic compounds across tubular epithelial cells is an important function of the kidney. This uni-directed transport is mediated by two cooperative functions, which are membrane potential-dependent organic cation transporters at the basolateral membranes and H+/organic cation antiporters at the brush-border membranes. More than 10 years ago, the basolateral organic cation transporters (OCT1-3/SLC22A1-3) were isolated, and molecular understandings for the basolateral entry of cationic drugs have been greatly advanced. However, the molecular nature of H+/organic cation antiport systems remains unclear. Recently, mammalian orthologues of the multidrug and toxin extrusion (MATE) family of bacteria have been isolated and clarified to function as H+/organic cation antiporters. In this commentary, the molecular characteristics and pharmacokinetic roles of mammalian MATEs are critically overviewed focusing on the renal secretion of cationic drugs. 相似文献