Effect of L-arginine on synaptosomal mitochondrial function

Objective: Specific aim of this study is to elucidate the direct effects of l-arginine on the synaptosomal neurotransmission related to the mitochondrial respiratory function. Methods: Using isolated endbrains from wild-type mice (ICR), crude synaptosome was analyzed for their concentration of γ-aminobutyric acid (GABA) and glutamate (Glu) with/without addition of l-arginine. We analyzed the contents of releasing amino acids evoked by high potassium condition and uptake of them in three separated fractions (cytosol, vesicles, and intact mitochondria). The oxygen consumption was also measured by oxygen electrode. Results: The entire uptakes of GABA and Glu were inhibited by rotenone (about 30 nmol/mg protein) with dose-dependent manner and showed a plateau at about 70% of total uptake. l-arginine inhibited the uptake of Glu logarithmically, however it showed no change in uptake of GABA. The contents of GABA and Glu in synaptosome were decreased in the presence of l-arginine. l-arginine enhanced the respiration of state II by succinate on synaptosomal respiration, although the respiration of synaptosomal mitochondrial fraction and the respiratory chains enzyme activities were almost unaffected by l-arginine. In the presence of rotenone, l-arginine decreased the uptake of Glu without changing the uptake of GABA, increased the releasing of GABA, and may modulate the excitability of neuronal state on the cytosol, cytomembrane, and/or organelles except for mitochondria. Conclusions:l-arginine may modulate excitation by neurotransmitters at nerve endings, in relation to potentiated respiratory metabolism of succinate in synaptosomes. Such effects might contribute to alleviation of stroke-like symptoms in MELAS.     

咪达唑仑对利多卡因致惊厥作用的影响

目的从致惊厥的行为学、安全性角度探讨咪达唑仑对利多卡因致惊厥作用的影响。方法皮下注射咪达唑仑20min后,腹腔注射不同剂量利多卡因,观察小鼠惊厥潜伏期、持续时间、未惊厥率及其死亡率;并按序贯法计算咪达唑仑对利多卡因致惊厥半数有效量（EDS0）和半数致死量（LD50）的影响。结果1．0mg／kg咪达唑仑可显著延长利多卡因致小鼠惊厥的潜伏期（P〈0．01）、显著缩短惊厥持续期（P〈0．01）、减少惊厥的发生;且2mg／kg、5mg／kg的咪达唑仑可减小利多卡因的LD50（P〈0．01）。结论1mg／kg咪达唑仑可拮抗利多卡因的致惊厥作用,结果对临床联合用药有一定的参考意义。     

c-FOS and n-NOS reactive neurons in response to circulating Phoneutria nigriventer spider venom

Drugs and neurotoxins activate specific neural circuits by increasing or decreasing the formation and release of neurotransmitters, such as nitric oxide (NO), and by inducing immediate early genes, such as FOS. We have previously shown that Phoneutria nigriventer spider venom (PNV) impairs the microtubule-dependent transcellular barrier of the blood-brain interface and causes structural alterations in perivascular astrocytic end-feet without producing morphological changes in central neuronal cells. In the present study, we used FOS and neuronal nitric oxide synthase (n-NOS) immunolabeling to investigate the ability of PNV to activate the central nervous system. Three groups of rats were used: the first group received a sublethal dose of PNV (850 microg/kg, via a tail vein), the second received an equal volume of 0.9% saline (sham group) and the third group received no injection. Envenomed rats showed salivation, lachrymation, tremors and flaccidity followed by spastic paralysis of the hind limbs and convulsions. Cryosections (30 microm thick) were serially collected at 600 microm intervals for free-floating immunohistochemical analysis. FOS-like positive neurons predominated in motor-related areas such as dorsolateral (dlPAG) and ventral periaqueductal gray matter (vPAG), frontal (FCM) and parietal motor cortex (PCM), and periventricular thalamic nucleus (PTN) and in acute stress-related areas (rhinal cortex and lateral septal nuclei). The greatest relative increases in FOS-like positive neurons occurred in the vPAG, PCM and PTN motor-related areas. n-NOS-positive neurons predominated in the periventricular thalamic nuclei, followed by the dorsolateral periaqueductal gray matter and parietal cortex motor area. The marked activation of motor areas and, to a lesser extent, of acute stress-related areas suggested the involvement of neuronal pathways in these regions in the response to envenoming by PNV. In addition, the occurrence of n-NOS immunolabeling in some anatomical regions with FOS-like positive neurons suggests that NO may modulate the response to PNV in these regions.     

Ovariectomy aggravates convulsions and hippocampal γ-aminobutyric acid inhibition induced by cyclosporin A in rats

The possible cyclosporin A application for rheumatoid arthritis that develops preferentially in middle-aged women raises concerns about adverse effects of cyclosporin A, including neurotoxicity in patients with climacterium. The present study was aimed at elucidating the effect of cyclosporin A on the convulsive activity and γ-aminobutyric acid (GABA) neural activity of the hippocampus in ovariectomized rats, as a menopause/climacterium model. Ovariectomy markedly aggravated the effect of repeated administration of cyclosporin A (40 mg/kg, once a day for 5 or 6 days), convulsions and reduction of the basal GABA levels and aminooxyacetic acid-evoked GABA accumulation. These aggravations were blocked by estradiol replacement. The present findings demonstrated that ovariectomy increased the susceptibility to cyclosporin A-induced convulsions by accelerating an inhibitory action of cyclosporin A on GABA neural activity in the hippocampus, this being blocked by estrogen replacement. Menopause/climacterium is, therefore, included in the risk factors for cyclosporin A-induced neurotoxicity and this risk is lowered by estrogen replacement therapy.     

热性惊厥儿童IMPA2基因多态性分析

目的:分析IMPA2基因多态性与儿童热性惊厥易感性的关系。方法:采用病例-对照研究方法和聚合酶链反应-限制片断长度多态分析技术(PCR-RFLP),检测热性惊厥病例组和健康对照组的IMPA2基因多态性。结果:IMPA2基因单核甘酸多态性位点159T>C病例组与对照组基因型分布无显著差异,而单核甘酸多态性位点558C>T病例组与对照组基因型分布有显著差异(P<0.01)。结论:IMPA2的基因位点558C>T可能是热性惊厥的多基因遗传位点之一。     

Convulsant activity of sitafloxacin and its interactions with anti-inflammatory drugs in mice

We studied the convulsant activity of sitafloxacin, a newly developed quinolone, and its interaction with anti-inflammatory drugs in mice. Intraventricular injections of sitafloxacin and levofloxacin induced convulsions dose-dependently in the mice. The value of the effective dose for producing convulsions in 50% of the mice (ED₅₀) of sitafloxacin was 50.6 nmol/head, whereas that of levofloxacin was 76.7 nmol/head. The convulsant activity of these quinolones was not affected by concurrent administration with anti-inflammatory drugs. From these results obtained in a mouse model, it is suggested that sitafloxacin has weak convulsant activity and that the convulsant activity of sitafloxacin is not enhanced when it is administered with anti-inflammatory drugs.     

88例热性惊厥患儿缺铁性贫血相关指标分析

目的了解热性惊厥与缺铁性贫血的关系。方法检测88例热性惊厥患儿的红细胞计数、血红蛋白、红细胞平均容积、红细胞平均血红蛋白、红细胞平均血红蛋白浓度、血清铁、血清铁蛋白,并以同期住院的76例呼吸道、肠道感染而无惊厥患儿为对照组,将两组数据进行统计分析。结果热性惊厥组缺铁性贫血的发生率为61.36%,对照组为43.42%,血红蛋白、血清铁含量与对照组有显著性差异(P<0.05);而且复杂型热性惊厥的缺铁性贫血的发生率占85%,与单纯型比较亦有显著性差异(P<0.05)。结论血清铁与小儿热性惊厥密切相关,缺铁性贫血可能是引起热性惊厥的原因之一。     

针药结合治疗小儿高热惊厥的疗效观察

目的　观察醒脑开窍针刺法配合安定针治疗小儿高热惊厥疗效及安全性。方法　 6 0例高热惊厥患儿按随机数字表法随机分成两组 ,每组 30例 ,针药组采用针刺醒脑开窍法配合安定静脉推注 ,药物组单纯采用安定 ,观察止痉起效时间、复发率及呼吸抑制情况。结果　在止痉起效时间和复发率上 ,针药组明显少于药物组 ,两组均未发现呼吸抑制情况。结论　针刺配合安定针治疗高热惊厥是一种快速、有效、安全的方法。     

依托咪酯对布比卡因致惊厥作用的影响

目的观察依托咪酯（etomidate,Eto）对布比卡因（bupivacaine,Bup）致惊厥作用及半数有效量（ED50）、半数致死量（LD50）的影响。方法皮下注射3种不同剂量的依托咪酯20min后,腹腔注射致惊厥作用的布比卡因,观察小鼠惊厥潜伏期、持续时间、未惊厥数和死亡数;并以序贯法测定预先给予依托咪酯20min后布比卡因的致惊厥ED50和LD50。结果依托咪酯2、4mg/kg可延长布比卡因致小鼠惊厥的潜伏期（P〈0.01）,缩短持续时间（P〈0.01）,减少惊厥发生数和死亡数;增大布比卡因致惊厥的ED50（P〈0.05,P〈0.01）,增大布比卡因的LD50（P〈0.01）。结论依托咪酯能够拮抗布比卡因的致惊厥作用,降低布比卡因的毒性。     

神经肽Y在惊厥性疾病患儿血浆和脑脊液中质量浓度变化及临床意义

目的观察血浆、脑脊液中神经肽Y(NPY)的质量浓度变化，探讨NPY在惊厥性疾病中的作用及临床意义。 方法选取2002 09—2003 08在陕西省人民医院儿科住院的惊厥性疾病患儿,采用放射免疫分析方法检测血浆和脑脊液中NPY的质量浓度。 结果(1)惊厥组血浆中NPY质量浓度第7天较第1天增高，差异有显著性(t=5366,P<001)，惊厥组各组第7天与第1天自身比较差异有显著性(t=3509,3480,3379,P<005)；脑炎无惊厥组第7天较第1天增高，但差异无显著性(t=1056,P=0309)；惊厥组与脑炎无惊厥组、对照组相比,差异有显著性(t=5728,P<001；t=6990,P<0001)，脑炎无惊厥组与对照组比较差异无显著性意义(t=0987,P>005)，惊厥组各组之间差异也有显著性(F=34674,P<001)。(2)惊厥组脑脊液中NPY质量浓度与脑炎无惊厥组、对照组比较差异有显著性(t=7830，5699，P<0001)，脑炎无惊厥组与对照组比较差异无显著性(t=0112，P=0911)，惊厥组各组之间差异也有显著性(F=68931，P<001)。(3)血浆和脑脊液中NPY质量浓度与惊厥发作次数有关(P<005),与性别、年龄、体重无显着相关，P均大于005;第1、7天血浆NPY质量浓度与第1天脑脊液NPY质量浓度有显着正相关性(r=0954，P<0001;r=0950，P<0001)。 结论(1)惊厥性疾病患儿血浆、脑脊液中NPY质量浓度均增高，与惊厥发作次数有关，但在惊厥发生的不同阶段质量浓度不同。(2)血浆与脑脊液中NPY质量浓度呈正相关性，血浆中的质量浓度能间接反映脑脊液质量浓度。提示动态监测NPY质量浓度可能有助于对惊厥的临床诊断、治疗及预后的判断。