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101.
Toivo Halonen† Asla Pitkanen Esa Koivisto Juhani Partanen‡ Paavo J. Riekkinen 《Epilepsia》1992,33(1):122-127
Vigabatrin (gamma-vinyl GABA; GVG) is a new antiepileptic drug (AED) that increases the level of the inhibitory transmitter, gamma-aminobutyric acid (GABA) in the brain. We evaluated the effect of GVG on the EEG of normal rats. GVG was administered intraperitoneally (i.p.) at a dose of 100 mg/kg once a day for 12 days. EEG was recorded at baseline, on the fourth day, at the end of the 12-day GVG period and 10 days after discontinuation of GVG. GVG increased the amplitude of delta (1-4 Hz) and theta (4-8 Hz) frequency bands and resulted in slowing of the peak frequency (Fp) and mean frequency (Fm) in both the frontal and occipital cortex, especially during waking-immobility. EEG changes normalized within 10 days after the last GVG injections. The results suggest that a relationship may exist between the EEG changes and increase in GABA levels with GVG. 相似文献
102.
To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia. 相似文献
103.
Jose Rodriguez Wendy Jacques-Berg Coral Sanfeliu Ambrish J. Patel 《Brain research》1992,590(1-2):109-117
The possible involvement of ionotropic and metabotropic quisqualate (QA) receptors in neuronal plasticity was studied in cultured glutamtergic cerebellar or hippocampal cells in terms of the specific activity of phosphate-activated glutaminase, an enzyme important in the synthesis of the putative neurotransmitter pool of glutamate. When cerebellar of hippocampal neurons were treated with QA, it elevated the specific activity of glutaminase in a dose-dependent manner. The half-maximal effect was obtained at about 0.1 μM, the maximum increase was at about 1 μM, but levels higher than 10 μM QA produced progressive reduction in glutaminase activity. In contrast, QA had little effects on the activities of lactate dehydrogenase and aspartate aminotransferase and the amount of protein, indicating that the increase in glutaminase was relatively specific. The QA-mediated increase in glutaminase was mimicked by the ionotropic QA receptor agonist -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; EC50, about 0.5 μM), but not by the metabotropic QA receptor agonist trans-(±)-1-aino-cyclopentyl-1,3,dicarboxyalte (t-ACPD; up to 0.5 mM). The specific ionotropic QA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited QA- and AMPA-mediated increases in glutaminase activity in a dose-dependent manner, whereas other glutamate receptor antagonists,
-2-amino-5-phosphonovalerate, γ-
-glutamyl aminomethyl sulphonic acid and γ-
-glutamyl diethyl ester were ineffective. The elevation of neurotransmitter enzyme was Ca2+-dependent. The increase in Ca2+ influx essentially through the activation of L-type voltage-operated Ca2+ channels, and not the mobilization of internal Ca2+ stores, was responsible for these QA receptor-mediated long-term plastic changes in hippocampal and cerebellar neurons. 相似文献
104.
为探索天然超氧化物岐化酶(SOD)岐化超氧离子的机理,及用于临床的可能性,我们合成了乳酸、柠檬酸和酒石酸的锰(Ⅱ)配合物作为Mn-SOD的模拟物,用光照法测定了它们的活性,得到了有意义的结果:锰配合物作为Mn-SOD的模拟物,有肯定的活性,其中以乳酸锰配合物活性最高。 相似文献
105.
J. P. De La Cruz S. Cámara M. A. Frutos F. Sánchez De La Cuesta 《European journal of clinical pharmacology》1992,43(3):307-309
Summary The antiproteinuric effect of the antiplatelet agent dipyridamole has been assessed after inhibiton of thromboxane B2 (TxB2) synthesis in 8 patients with confirmed membranous glomerulonephritis.
There were three study periods, each of 30 days, and 45 days apart, namely a washout period, treatment with dipyridamole 300
mg/d, and dipyridamole 225 mg/d plus aspirin 150 mg/d. On Days 1 and 30 of each study period serum and urine creatinine, 24-h
excretion of protein, creatinine clearance, platelet aggregometry on whole blood and serum TxB2 were measured.
Treatment with dipyridamole alone or with aspirin produced significant inhibition of platelet aggregation and a fall in 24-h
protein excretion; the latter amounted to 54% with dipyridamole alone and 56 % with dipyridamole plus aspirin (NS). Dipyridamole
plus aspirin caused an 82 % reduction in serum TxB2. 相似文献
106.
Toshio Kawai Kazunori Mizunuma Tomojiro Yasugi Shun'ichi Horiguchi Masayuki Ikeda 《International archives of occupational and environmental health》1994,66(5):309-315
The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels. 相似文献
107.
Jason N. MacLean Brian J. Schmidt Shawn Hochman 《The European journal of neuroscience》1997,9(12):2702-2711
Whole-cell recordings of lumbar motoneurons in the intact neonatal rat spinal cord in vitro were undertaken to examine the effects of Kmethyl-D-aspartate (NMDA) receptor activation on membrane behaviour. Bath application of NMDA induced rhythmic voltage oscillations of 5.9 ± 2.1 mV (SD) at a frequency of 4.4 ± 1.5 Hz. Amplitude, but not frequency, of the voltage oscillations was membrane potential-dependent. Voltage oscillations could recruit action potentials and/or plateau potentials with or without superimposed bursting. Blockade of synaptic transmission with tetrodotoxin (TTX) sometimes resulted in a loss of oscillatory activity which could then be restored by increasing the NMDA concentration. After application of TTX, the trajectory of NMDA-induced oscillations was similar to the trajectory induced in the presence of intact synaptic networks, although the mean oscillation duration was longer and the oscillation frequency was slower (1.8 ± 1.1 Hz). Current ramps delivered after bath application of NMDA demonstrated bistable membrane properties which may underlie the plateau potentials. Injection of intracellular current pulses could initiate, entrain and terminate individual plateau potentials. The results suggest that membrane depolarization produced by oscillations may activate other intrinsic conductances which generate plateau potentials, thereby providing the neuron with enhanced voltage sensitivity, compared to that produced by NMDA receptor activation alone. These oscillatory events may have a role in the regulation of motor output in a variety of rhythmic behaviours including locomotion. 相似文献
108.
Circling behavior in honey bees 总被引:1,自引:0,他引:1
Unilateral microinjections of gamma-aminobutyric acid (GABA), acetylcholine (ACh) and related substances into central parts of the brain of the honey bee elicit a quantifiable circling behavior. GABA (40 nl, 10(-2) M, muscimol (40 nl, 10(-4) M) and flaxedil (10(-3) M, 40 nl) induce contralateral circling whilst ACh (40 nl, 10(-2) M), nicotine (40 nl, 10(-4) M) and picrotoxin (40 nl, 10(-3) M) induce ipsilateral circling if injected in the proximity of the alpha-lobe (50-100 microns) of the of the mushroom body. Mechanical lesions of the pedunculus induce ipsilateral circling. This can be reversed by ipsilateral injections of GABA and flaxedil. Intracellular recordings demonstrate a hyperpolarizing effect of GABA and a depolarising effect of ACh on individual neurons in this region. These results suggest that circling behavior in the bee is controlled by the balance of GABA in the alpha-lobes and mediated by acetylcholinergic neurons. 相似文献
109.
目的观察耐药乳腺癌细胞c-myc表达及其反义寡核苷酸对耐药的逆转效应,探讨c-myc在耐药调控中的作用。方法运用流式细胞仪检测乳腺癌耐药细胞MCF-7/Adr和其药敏亲本系MCF-7的c-myc表达水平。MTT法测定阿霉素作用于上述细胞的药物半数抑制浓度(IC50)。结果MCF-7/Adr耐药细胞c-myc的表达率为70.48%,其亲本药敏细胞系MCF-7c-myc表达率仅46.02%,前者显著高于后者(P<0.05)。阿霉素单独作用于MCF-7/Adr,IC50值为(22.00±1.92)μmol/L,但与4μmol/Lc-myc反义寡核苷酸共孵育后,阿霉素的IC50值则显著下降为(9.60±1.04)μmol/L。结论与其亲本药敏细胞相比较,MCF-7/Adr的c-myc表达显著上调,抑制c-myc的过表达可部分逆转MCF-7/Adr的阿霉素抵抗,提示c-myc参与肿瘤耐药的发生。 相似文献
110.
Intraparenchymal fetal striatal transplants and recovery in kainic acid lesioned rats 总被引:1,自引:0,他引:1
Striatal kainic acid (KA) lesions induce behavioral and biochemical deficits which resemble symptoms encountered in patients suffering from Huntington's disease. In rats with KA lesions, fetal striatal transplants have shown to reverse the pervasive nocturnal hyperactivity induced by the lesion. In the present study 4.6 mm3 of fetal striatal tissue were delivered bilaterally into the anterodorsal portion of the lesioned caudate nucleus. Care was taken to deliver the transplant within the host parenchyma and away from the lateral ventricles. Locomotor behavior analyzed using the Digiscan animal activity monitors before and after the transplants demonstrated a reversal of the hyperactivity following transplants in 70% of lesioned animals. Microinjections of horseradish peroxidase delivered into the globus pallidus and substantia nigra of a small group of functionally recovered transplanted animals, did not reveal evidence for reinnervation between host nigra or pallidum and the transplant at 10 weeks post-transplantation. Other laboratories have reported anatomical connections by 6 months post-transplantation. Ventricular/brain ratios demonstrated that intraparenchymal transplants significantly reduced the ventricular dilation following KA lesion. These results suggest that functional recovery can be obtained when the transplant is immersed into the host's striatal parenchyma regardless of the existence of long-range anatomical connections. 相似文献