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1.
Transport of bretylium into adrenergic neurons was studied, using rabbit isolated periarterial nerve ileum preparations, by determining the effects of various incubation procedures, which inhibit noradrenaline uptake, to prevent or reverse the blockade. Adrenergic neuron blockade by bretylium 5 X 10(-5) (g/ml) was prevented but not reversed by incubation with sodium free and low temperature (10 degrees C) media. Ouabain 2.2 X 10(-8) and anoxia prevented bretylium-induced blockade. Noradrenaline 5 X 10(-6) and 8 X 10(-5) prevented and also reversed the blockade, but the reversing effect was transient. High calcium (totally 10 mM) readily reversed the bretylium-induced blockade, the recovery being complete and long-lasting. In light of the results, a sodium sensitive active transport of bretylium into adrenergic neurons is apparently necessary for development of adrenergic neuron blocking action in rabbit ilea. 相似文献
2.
L Gandía M Villarroya F Sala JA Reig S Viniegra JL Quintanar AG García LM Gutiérrez 《Canadian Metallurgical Quarterly》1996,118(5):1301-1307
1. The effects of diltiazem on various functional parameters were studied in bovine cultured adrenal chromaffin cells stimulated with the nicotinic receptor agonist dimethylphenylpiperazinium (DMPP) or with depolarizing Krebs-HEPES solutions containing high K+ concentrations. 2. The release of [3H]-noradrenaline induced by DMPP (100 microM for 5 min) was gradually and fully inhibited by increasing concentrations of diltiazem (IC50 = 1.3 microM). In contrast, the highest concentration of diltiazem used (10 microM) inhibited the response to high K+ (59 mM for 5 min) by only 25%. 3. 45Ca2+ uptake into cells stimulated with DMPP (100 microM for 1 min) was also blocked by diltiazem in a concentration-dependent manner (IC50 = 0.4 microM). Again, diltiazem blocked the K(+)-evoked 45Ca2+ uptake (70 mM K+ for 1 min) only by 20%. In contrast, the N-P-Q-type Ca2+ channel blocker omega-conotoxin MVIIC depressed the K+ signal by 70%. In the presence of this toxin, diltiazem exhibited an additional small inhibitory effect, indicating that the compound was acting on L-type Ca2+ channels. 4. Whole-cell Ba2+ currents through Ca2+ channels in voltage-clamped chromaffin cells were inhibited by 3-10 microM diltiazem by 20-25%. The inhibition was readily reversed upon washout of the drug. 5. The whole-cell currents elicited by 100 microM DMPP (IDMPP) were inhibited in a concentration-dependent and reversible manner by diltiazem. Maximal effects were found at 10 microM, which reduced the peak IDMPP by 70%. The area of each curve represented by total current (QDMPP) was reduced more than the peak current. At 10 microM, the inhibition amounted to 80%; the IC50 for QDMPP inhibition was 0.73 microM, a figure close to the IC50 for 45Ca2+ uptake (0.4 microM) and [3H]-noradrenaline release (1.3 microM). The blocking effects of diltiazem developed very quickly and did not exhibit use-dependence; thus the drug blocked the channel in its closed state. The blocking effects of 1 microM diltiazem on IDMPP were similar at different holding potentials (inhibition by around 30% at -100, -80 or -50 mV). Diltiazem did not affect the current flow through voltage-dependent Na+ channels. 6. These data are compatible with the idea that diltiazem has little effect on Ca2+ entry through voltage-dependent Ca2+ channels in bovine chromaffin cells. Neither, does diltiazem affect INa. Rather, diltiazem acts directly on the neuronal nicotinic receptor ion channel and blocks ion fluxes, cell depolarization and the subsequent Ca2+ entry and catecholamine release. This novel effect of diltiazem might have clinical relevance since it might reduce the sympathoadrenal drive to the heart and blood vessels, thus contributing to the well established antihypertensive and cardioprotective effects of the drug. 相似文献
3.
We examined the effect of nitrous oxide (N2O) administration on the level of sensory block produced by intrathecal lidocaine in patients undergoing transurethral procedures. Twenty minutes after subarachnoid injection of 100 mg (5%) hyperbaric lidocaine, the level of block to pressure sensation was assessed. After establishing the baseline sensory block, patients were randomly assigned to receive either 50% nitrogen (control group) or 50% N2O in oxygen for 10 min, and the sensory level was reassessed. All patients then received 35% oxygen for 5 min, and the level of block to pressure was assessed again. Changes were measured in centimeters and standardized by dividing those results by the height of patients (in centimeters). Ten minutes after nitrogen or N2O administration, a 3.8-cm regression of sensory block was found in the control group, and a 1.8-cm cephalad increase was found in the treatment group (P < 0.0001). Discontinuation of N2O for 5 min resulted in a rapid regression of the level of sensory block (4 cm in the N2O group versus 1.9 cm in the control group, P < 0.0001). However, 5 min after discontinuation of N2O, the overall regression of the sensory block in the control group, when measured from the baseline, was 5.7 cm versus 2.2 cm in the N2O group (P < 0.001). The differences between the two groups before standardization are consistent with those after standardization (t = 9.02 at 10 min, t = 4.24 at 15 min, and t = 3.97 for the overall change at 15 min). The results suggest that inhalation of 50% N2O enhances the level of sensory block produced by intrathecal lidocaine. IMPLICATIONS: We measured the level of sensory block produced by subarachnoid anesthesia with lidocaine before and after inhalation of 50% nitrous oxide for 10 min. Nitrous oxide enhanced the level of subarachnoid anesthesia with minimal hemodynamic effects. These findings are of clinical importance when subarachnoid anesthesia subsides before the completion of surgery. 相似文献
4.
R Gáspár G Panyi DL Ypey Z Krasznai G Vereb C Pieri S Damjanovich 《Canadian Metallurgical Quarterly》1994,46(4):762-766
Using the patch-clamp technique, we determined that bretylium tosylate, a quaternary ammonium compound possessing immunomodulating activity, decreased the whole-cell K+ current in human T lymphocytes, in a dose-dependent manner, in the 0.05-5 mM extracellular concentration range. Bretylium tosylate prolonged the recovery from inactivation and accelerated the inactivation and deactivation of the K+ current but did not influence the kinetics of activation or the voltage dependence of activation and steady state inactivation of the K+ conductance. The percentage of drug-induced block was independent of membrane potential. K+ channel block by bretylium tosylate was partially and slowly removable by washing with drug-free extracellular solution. Bovine serum albumin (10 mg/ml) in the bath lifted the drug-induced block almost instantaneously, although not completely. In control experiments bovine serum albumin increased the inactivation time constant of the K+ channels but left the peak K+ current amplitude unaffected. On the basis of the experimental evidence, a gating-dependent allosteric interaction is suggested for the mechanism of drug action. The effective dose range, time of exposure, and reversibility of bretylium tosylate-induced K+ channel block correlated well with the same parameters of the drug-induced inhibition of T lymphocyte activation. The reported effects of bretylium tosylate on T cell mitogenesis can be regarded partly as a consequence of its blocking effects on voltage-gated K+ channels. 相似文献
5.
Clinical picture of development of segmental blocking after subarachnoidal injection of hyperbaric solutions of 0.75% bupivacaine, 5% ultracaine, and isobaric 0.5% bupivacaine is studied. A total of 152 patients operated on the lower part of the body and the lower limbs were examined under conditions of single, prolonged subarachnoidal, and combined spinal epidural anesthesia. Ultracaine and bupivacaine in different concentrations with different barism provided anesthesia equivalent by the efficacy, depth, and dissemination of sensory block. Segmental blocking with 5% ultracaine was characterized by the shortest latent period (3.14 +/- 0.16 min, p < 0.05) but was no shorter (124.1 +/- 3.37 min) than operative analgesia with 0.75% hyperbaric bupivacaine (120.0 +/- 5.10 min). Isobaric bupivacaine provided the longest effective analgesia (215.0 +/- 45.0 min, p < 0.05). Microcatheter technique improved the safety and control of subarachnoidal anesthesia in comparison with a single injection, and combined spinal epidural anesthesia shortened the latent period of segmental blocking and ensured intraoperative anesthesia and postoperative analgesia at the expense of the epidural component. 相似文献
6.
FJ Caliendo VJ Halpern CP Marini IM Nathan D Patel G Faust JR Cohen 《Canadian Metallurgical Quarterly》1999,13(1):11-16
A useful correlation between maximum thyroid uptake and radioiodine urine levels at different times after exposure was developed in order to determine when the intervention with an adequate blocking agent might still be effective. In an animal model (dog), six different doses were administered in the range of 100-600 kBq. The best correlation was found between the 125I uptake after 48 h (T-48) and urine radioactivity 4-6 h (U-4, U-5, U-6) after exposure. For the case of U-4, the equation Y(T-48) = 0.790 X(U-4) + 2.973 (r = 0.974 with a level of significance of p < 0.001) was obtained. An analogous study, carried out in humans (n = 20) to whom 1311 was administered, showed a similar correlation and level of significance: Y(T-24) = 1.162 X(U-4)+3.263 (r = 0.926; p < 0.001). The validity of this correlation was confirmed in four volunteers who received small doses of 125I(25-100 kBq), with good agreement between measured and extrapolated thyroid uptake and a mean difference of less than 10% (CV = 16.2%). Three different blocking agents were then tested in the same dog: potassium iodide, potassium perchlorate, and a thionamide (Tapazole). The blocking action of the first two compounds was about 90%, as opposed to only 48% for the third compound. Potassium iodide was chosen for its limited side effects and more universal utilization. The final study, carried out with four different doses, indicated that 25 mg of KI is the ideal amount to be administered to the dog. This corresponds to approximately 100 mg for a 70 kg human being (i.e., 1.4 mg kg(-1)). This dose, when administered to a volunteer 4 h after exposure, provided a thyroid blocking of 68%. 相似文献
7.
Iodine-123-metaiodobenzylguanidine [123I-MIBG] has been used to evaluate the cardiac sympathetic nervous system. We evaluated the effect of pulmonary hypertension on the sympathetic neuronal function of the left ventricle in patients with pulmonary hypertension. We studied 20 patients with either chronic lung disease or pulmonary vascular disease. The patients were divided into a pulmonary hypertensive group and a control group. Single photon emission tomography was performed in the resting state 15 min and 4 h after administration of 123I-MIBG. Regions of interest (ROI) were set in the left ventricular (LV) free wall, the interventricular septum (IVS) and outside the LV free wall on short-axis images. The washout rate and the ROI/LV uptake ratio were calculated in each ROI. The IVS:LV uptake ratio was significantly lower in the pulmonary hypertensive group than in the control group. Our results suggest that left heart sympathetic neuronal dysfunction initially occurs in the IVS before it involves the LV free wall subsequently. 相似文献
8.
DM Raffel JR Corbett RB del Rosario DL Gildersleeve PC Chiao M Schwaiger DM Wieland 《Canadian Metallurgical Quarterly》1996,37(12):1923-1931
The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. METHODS: Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. RESULTS: No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. CONCLUSION: PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED. 相似文献
9.
G Rossoni A Sala F Berti T Testa C Buccellati C Molta R Muller-Peddinghaus J Maclouf GC Folco 《Canadian Metallurgical Quarterly》1996,276(1):335-341
Perfusion of the isolated rabbit heart with 5 x 10(6) human polymorphonuclear leukocytes, under recirculating conditions (50 ml), and challenge with A-23187 (0.5 microM) caused an increase in coronary perfusion pressure (from a prechallenge value of 46 +/- 1.1 to 176.2 +/- 29.7 mm Hg, 30 min after challenge, n = 6-4), which was linearly correlated (P < .006) with formation of cysteinyl leukotrienes (29.7 +/- 7.3 pmol/ml, 30 min after challenge). Pretreatment with the leukotriene synthesis inhibitor BAY X1005 (1 microM) (n = 6) resulted in significant protection against the increase in coronary perfusion pressure (76.7 +/- 12.8 mm Hg, 30 min after challenge) and in almost complete inhibition of sulfidopeptide leukotriene synthesis (3.2 +/- 1.7 pmol/ml, 30 min after challenge). In in vivo experiments, ligation of the left anterior descending coronary artery in the rabbit (n = 10) resulted in acute myocardial infarction marked by a mortality rate of 60% compared with sham-operated animals (n = 10). Intravenous treatment of the rabbits with BAY X1005 (10 mg/kg/h, for 2 h) (n = 10) markedly reduced the mortality rate (20%), protected the rabbits against the marked electrocardiogram derangement and abolished the significant increase in plasma creatine phosphokinase activity and cardiac tissue myeloperoxidase activity induced by coronary artery ligation. BAY X1005 exerts a significant cardioprotection and suggests that specific leukotriene synthesis inhibitors may lead to innovative therapy in myocardial ischemia. 相似文献
10.
The beta-adrenoreceptor blocking agent propranolol was shown to activate noradrenaline-N3 absorption by the rat isolated organs by 30-180%. The alpha-adrenoreceptor blocking agent phentolamine only activated by 30-55% the noradrenaline-N3 absorption in the organs possessing the postsynaptic alpha-adrenoreceptors (ductus semen, spleen and amsll intestine). The beta-adrenoreceptor activator isopropylnoradrenaline decreased the intensity of noradrenaline-N3 absorption in all the organs by 15-50%. The alpha-adrenoreceptor activating agents (urine and mesaton) only depressed the noradrenaline-N3 absorption by 20-45% in the organs possessing postsynaptic alpha-adrenoreceptors. The data obtained suggest existence of reverse transsynaptic regulatory effects via adrenoreceptors of the cell-effector on the processes of noradrenaline absorption by adrenergic neuron. 相似文献
11.
CY Spong C Rasul JV Collea GS Eglinton A Ghidini 《Canadian Metallurgical Quarterly》1998,15(6):369-374
Primary neuronal injury due to acute traumatic brain-injury may cause significant damage to the CNS. However, impaired cognitive and behavioral function also occurs following secondary neuronal injury. Neuroprotective agents should be administered soon after the acute event to prevent this secondary phase. NMDA receptor antagonists, free radical scavengers and bradykinin antagonists are designed to protect the neuron from the damaging effects of mediators. Calcium-channel blocking agents and drugs promoting anaerobic glycolysis are designed to stop the intracellular processes causing ischemia. The standard treatment options for patients with brain injuries are limited. Thus, the possibility exists for poor outcomes. At this time, since there are no approved neuroprotective drugs available, experimental treatment offers a chance for improved outcomes. 相似文献
12.
OBJECTIVE: The therapeutic effects of methylphenidate in the treatment of attention deficit disorder have been attributed to its ability to increase the synaptic concentration of dopamine by blocking the dopamine transporters. However, the levels of dopamine transporter blockade achieved by therapeutic doses of methylphenidate are not known. This study measured, for the first time, dopamine transporter occupancy by orally administered methylphenidate in the human brain and its rate of uptake in the brain. METHOD: Positron emission tomography (PET) and [11C]cocaine were used to estimate dopamine transporter occupancies after different doses of oral methylphenidate in seven normal subjects (mean age=24 years, SD=7). In addition, the pharmacokinetics of oral methylphenidate were measured in the baboon brain through use of PET and [11C]methylphenidate administered through an orogastric tube. RESULTS: At 120 minutes after administration, oral methylphenidate produced a dose-dependent blockade of dopamine transporter; means=12% (SD= 4%) for 5 mg, 40% (SD=12%) for 10 mg, 54% (SD=5%) for 20 mg, 72% (SD=3%) for 40 mg, and 74% (SD=2%) for 60 mg. The estimated dose of oral methylphenidate required to block 50% of the dopamine transporter corresponded to 0.25 mg/kg. Oral methylphenidate did not reach peak concentration in brain until 60 minutes after its administration. CONCLUSIONS: Oral methylphenidate is very effective in blocking dopamine transporters, and at the weight-adjusted doses used therapeutically (0.3 to 0.6 mg/kg), it is likely to occupy more than 50% of the dopamine transporters. The time to reach peak brain uptake for oral methylphenidate in brain corresponds well with the reported time course to reach peak behavioral effects. 相似文献
13.
The hypothesis that there are differences in decompression risk between He and H2 was examined in 1,607 unanesthetized male albino rats subjected to dives on 2% O2-balance He or 2% O2-balance H2 (depths < or = 50 ATA, bottom times < or = 60 min). The animals were decompressed to 10.8 ATA with profiles varying from rapid to slow, with up to four decompression stops of up to 60 min each. Maximum likelihood analysis was used to estimate the relative decompression risk on a per unit pressure basis (termed "potency") and the rate of gas uptake and elimination, both factors affecting the decompression sickness risk, from a specific dive profile. H2 potency for causing decompression sickness was found to be up to 35% greater than that for He. Uptake rates were unresolvable between the two gases with the time constant (TC) estimated at approximately 2-3 min, leading to saturation in both cases in < 15 min. Washout of both gases was significantly slower than uptake, with He washout (TC approximately 1.5-3 h) substantially slower than H2 washout (TC approximately 0.5 h). It is unknown whether the decompression advantage of the faster washout of H2 or the disadvantage of its increased potency, observed in the rat, would be important for human diving. 相似文献
14.
BACKGROUND: Volatile general anesthetics depress neuronal activity in the mammalian central nervous system and enhance inhibitory Cl- currents flowing across the gamma-aminobutyric acid A (GABA(A)) receptor-ion channel complex. The extent to which an increase in GABA(A)-mediated synaptic inhibition contributes to the decrease in neuronal firing must be determined, because many further effects of these agents have been reported on the molecular level. METHODS: The actions of halothane, isoflurane, and enflurane on the firing patterns of single neurons were investigated by extracellular recordings in organotypic slice cultures derived from the rat neocortex. RESULTS: Volatile anesthetics depressed spontaneous action potential firing of neocortical neurons in a concentration-dependent manner. The estimated median effective concentration (EC50) values were about one half the EC50 values for general anesthesia. In the presence of the GABA(A) antagonist bicuculline (20 microM), the effectiveness of halothane, isoflurane, and enflurane in reducing the discharge rates were diminished by 48-65%, indicating that these drugs act via the GABA(A) receptor. CONCLUSIONS: Together with recent investigations, our results provide evidence that halothane, isoflurane, and enflurane reduced spontaneous action potential firing of neocortical neurons in cultured brain slices mainly by increasing GABA(A)-mediated synaptic inhibition. At concentrations, approximately one half the EC50 for general anesthesia, volatile anesthetics increased overall GABA(A)-mediated synaptic inhibition about twofold, thus decreasing spontaneous action potential firing by half. 相似文献
15.
HM Dey PB Hoffer E Lerner IG Zubal JF Setaro HR Black 《Canadian Metallurgical Quarterly》1993,34(9):1416-1419
Retrospective analysis of precaptopril and postcaptopril DTPA renograms from 88 hypertensive patients was performed to refine the quantitative criteria used to diagnose renal artery stenosis (RAS). Of the 88 patients, 45 had RAS and 43 had normal renal arteries at angiography. Using time-activity curves from the essential hypertensive group, diagnostic washout criteria for a positive DTPA renogram were developed. These were based on the 20 and 30 min/peak activity ratios in each kidney. When the washout criteria were retrospectively applied to patient data as a whole, sensitivity and specificity for RAS were 67% and 79%, respectively. When previously described uptake criteria, based on the time to peak activity in each kidney and the GFR ratio between the kidneys, were applied to the same data, sensitivity and specificity for RAS were 89% and 84%, respectively. Quantitative analysis of the DTPA renogram using the time to peak and GFR ratio was both sensitive and specific for RAS. Measurement of 20 and 30 min/peak renal activity ratios did not improve the accuracy of the test. 相似文献
16.
FC Chiodini E Tassonyi T Fuchs-Buder M Fathi D Bertrand D Muller 《Canadian Metallurgical Quarterly》1998,88(4):1003-1013
BACKGROUND: Although neuromuscular blocking agents do not cross the blood-brain barrier, they may penetrate the central nervous system under particular circumstances and eventually cause neurotoxic consequences. METHODS: The effects of neuromuscular blocking agents on excitatory and inhibitory transmission in area CA1 of rat hippocampal slices were investigated using extracellular and intracellular recording techniques. RESULTS: Application of atracurium in the perfusion medium resulted in a dose-dependent enhancement of excitatory synaptic responses averaging 48.7 +/- 4.3% at a concentration of 10 nM. This effect was correlated with an increase in the size of the presynaptic fiber volley. Laudanosine, but not pancuronium bromide or vecuronium bromide, produced similar changes. In addition, atracurium and laudanosine blocked inhibitory transmission and reduced intracellularly recorded gamma-aminobutyric acidA receptor-mediated potentials. These effects were observed only at concentrations >1 microM and were not reproduced by pancuronium bromide and vecuronium bromide. CONCLUSIONS: Atracurium and its metabolite, laudanosine, contrary to pancuronium bromide and vecuronium bromide, produce two distinct effects on hippocampal slices. They enhance excitatory transmission and neuronal excitability and they block inhibitory gamma-aminobutyric acidA-mediated synaptic responses. 相似文献
17.
STUDY OBJECTIVE: To explore the value of high-dose methotrexate (MTX). SUBJECTS: Blast cells from 15 patients with acute lymphoblastic leukemia. INTERVENTIONS: We compared uptake and polyglutamation of [3H]-MTX by freshly isolated leukemic blasts in vitro after 24-hour exposure to 1, 10, and 50 microM [3H]-MTX. MEASUREMENTS AND MAIN RESULTS: Mean MTX uptake (pmol/10(6) cells) was 0.78 +/- 0.19, 2.3 +/- 0.54, and 5.9 +/- 1.9, respectively, and mean polyglutamation was 82%, 66%, and 46%. Consequently, mean MTX polyglutamates were 0.68 +/- 0.18, 1.5 +/- 0.47, and 2.2 +/- 0.67 pmol/10(6) cells. Three of 15 patient samples had no detectable polyglutamation of MTX at 50 microM but MTX polyglutamates were detectable at 1 microM. Two of these three had a decrease in MTX polyglutamates at 10 versus 1 microM. In eight precursor B cell samples there was a significant difference in median MTX polyglutamates at 1 versus 10 microM but not 10 versus 50 microM. CONCLUSION: Increasing extracellular MTX concentrations may be counterproductive for some patients with acute lymphoblastic leukemia. If MTX polyglutamates are important for efficacy, optimal delivery of MTX may have to be determined by individual metabolism rather than by targeting a specific drug concentration. 相似文献
18.
S Todoroki S Goto Y Urata K Komatsu K Sumikawa T Ogura I Matsuda T Kondo 《Canadian Metallurgical Quarterly》1998,4(8):515-524
Hereditary argininemia manifests as neurological disturbance and mental retardation, features not observed in other amino acidemias. The cytotoxic effect of a high concentration of L-arginine (L-Arg) was investigated using NB9 human neuroblastoma cells (NB9), which express neuronal nitric oxide synthase (nNOS). When the concentration of L-Arg in the medium increased from 50 microM to 2 mM after incubation for 48 hr, the intracellular concentration of L-Arg increased from 68.0 +/- 1 pmol/10(6) cells to 1310.0 +/- 5 pmol/10(6) cells and that of L-citrulline (L-Cit) from undetectable levels to 47.1 +/- 0.2 pmol/10(6) cells (mean +/- SD of three independent analyses). This increase in intracellular L-Arg levels caused a decrease in NOS activity by approximately 71%. Flow cytometric analysis showed that reactive oxygen species (ROS) are produced in NB9 exposed to 2 mM L-Arg. The production of ROS was abolished by a NOS inhibitor, NG-nitro-L arginine-methylester. Production of ROS was also observed when NB9 were treated with L-Cit for 48 hr. To investigate the effect of L-Cit on the activity of NOS, a kinetic study on nNOS was conducted using cellular extracts from NB9. The apparent Km value of nNOS for L-Arg was 8.4 microM, with a Vmax value of 8.2 pmol/min/mg protein. L-Cit competitively inhibited NOS activity, as indicated by an apparent Ki value of 65 nM. These results suggest that L-Cit formed by nNOS in L-Arg-loaded neuronal cells inhibits NOS activity and nNOS in these L-Arg-loaded cells functions as a NADPH oxidase to produce ROS, which may cause neurotoxicity in argininemia. 相似文献
19.
SS Liu RA Stevens J Vasquez TC Kao T Sheikh M Aasen K Frey 《Canadian Metallurgical Quarterly》1997,84(4):780-783
Epinephrine test doses may be administered during combined spinal-epidural anesthesia to determine intravascular placement of epidural catheters. This study was designed to determine systolic blood pressure (SBP) and heart rate (HR) responses to intravenous injection of epinephrine (15 microg) during spinal anesthesia. Twelve volunteers received three spinal anesthetics (lidocaine 100 mg, tetracaine 15 mg, and bupivacaine 15 mg) in a randomized, double blind, cross-over fashion. Epinephrine was administered prior to spinal anesthesia (control), 30 min after injection of spinal anesthesia, and at regression of sensory block to T-10. SBP was measured with a radial arterial catheter and HR with an electrocardiogram. Positive responses were defined as peak increase in SBP > or = 15 mm Hg or HR > or = 20 bpm after injection of epinephrine. Compared with control, peak SBP responses decreased by a mean of 12 mm Hg during spinal anesthesia with tetracaine and bupivacaine (P < 0.05). Peak HR responses decreased by 11 bpm during all three spinal anesthetics (P < 0.05). Incidences of detection of intravenous injection by positive SBP and HR responses ranged from 50% to 100% and were not significantly affected by spinal anesthesia. Spinal anesthesia reduces hemodynamic responses to intravenous epinephrine injection but is unlikely to reduce detection by positive SBP and HR criteria. 相似文献
20.
JM Bailey 《Canadian Metallurgical Quarterly》1997,85(3):681-686
The length of anesthetic administration influences the rate at which concentrations of anesthetics decrease after their discontinuation. This is true for both intravenous (I.V.) and inhaled anesthetics. This has been explored in detail for I.V. anesthetics using computer simulation to calculate context-sensitive half-times (the time needed for a 50% decrease in anesthetic concentration) and other decrement times (such as the times needed for 80% or 90% decreases in anesthetic concentration). However, decrement times have not been reported for inhaled anesthetics. In this report, published pharmacokinetic parameters and computer simulation were used to compare the context-sensitive half-times and the 80% and 90% decrement times of the expected central nervous system concentrations for enflurane, isoflurane, sevoflurane, and desflurane. The context-sensitive half-times for all four anesthetics are small (<5 min) and do not increase significantly with increasing duration of anesthesia. The 80% decrement times of both sevoflurane and desflurane are also small (<8 min) and do not increase significantly with duration of anesthesia. However, the 80% decrement times of isoflurane and enflurane increase significantly after approximately 60 min of anesthesia, reaching plateaus of approximately 30 and 35 min. The 90% decrement time of desflurane increased slightly from 5 min after 30 min of anesthesia to 14 min after 6 h of anesthesia. It remained significantly less than the 90% decrement times of sevoflurane, isoflurane, and enflurane, which reached values of 65 min, 86 min, and 100 min, respectively, after 6 h of anesthesia. IMPLICATIONS: The major differences in the rates at which desflurane, sevoflurane, isoflurane, and enflurane are eliminated occur in the final 20% of the elimination process. 相似文献