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1.
Labeled morphine, codeine, heroin, or methadone was injected as a bolus into the common carotid artery of the rat, and the rat was decapitated 15 seconds later. The brain uptake of the drug was calculated by measurement of the brain content of the drug as a percentage of a labeled, highly diffusible reference substance simultaneously injected. The uptake of morphine was below measurability; the uptake of codeine was 24 percent; heroin, 68 percent; and methadone, 42 percent. Brain uptakes of morphine and codeine were also studied after intravenous injection and correlated well with uptakes after carotid injection; the uptake of codeine being nearly complete by 30 seconds. These studies indicate that brain uptake of certain of these drugs is very rapid and that uptake of heroin injected intravenously is probably limited by the regional flow of blood in the brain. The possible relation of this rapid penetration of the blood-brain barrier by heroin to its strongly addictive properties is discussed.  相似文献   

2.
N-methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein PSD-95. This procedure dissociated NMDARs from downstream neurotoxic signaling without blocking synaptic activity or calcium influx. The peptides, when applied either before or 1 hour after an insult, protected cultured neurons from excitotoxicity, reduced focal ischemic brain damage in rats, and improved their neurological function. This approach circumvents the negative consequences associated with blocking NMDARs and may constitute a practical stroke therapy.  相似文献   

3.
重金属离子相互作用对Cu在鲫鱼组织中积累的影响   总被引:11,自引:0,他引:11       下载免费PDF全文
研究了重金属离子相互作用对其在鲫鱼组织中积累的影响,结果表明: 混合重金属离子相互作用对Cu在鲫鱼组织中积累的影响与离子的种类、数量及组织的类型有关.随着重金属离子种类的增加,相互作用对其积累的影响变得显著,Cu离子在鱼脑和肝脏中的积累浓度升高 ,在鳃中的积累降低,在肌肉中的积累无影响.重金属离子相互作用不会改变Cu在鲫鱼组织中的分布规律,Cu在鲫鱼组织中的积累顺序为肝脏>鱼鳃>鱼脑>肌肉.  相似文献   

4.
gamma-Hydroxybutyrate and ethanol, as well as gamma-butyrolactone and ethanol are potentiative with respect to duration of loss of the righting reflex (sleep time). The concentration of ethanol in the liver decreases from 30 to 90 minutes after rats are injected with ethanol, but there is no change when ethanol is injected with gamma-butyrolactone. In view of the fact that gamma-hydroxybutyrate is a natural intermediate in brain, the effects of ethanol on the central nervous system may be mediated through its interaction with gamma-butyrolactone.  相似文献   

5.
本试验旨在研究脱氧雪腐镰刀菌烯醇(DON)和黄曲霉毒素B1(AFB1)单一及联合染毒对小鼠脑组织病理变化、抗氧化性能和紧密连接蛋白mRNA表达量的影响。选取96只18日龄昆明系雄性小鼠,随机分为对照组、DON组、AFB1组和AD组(DON+AFB1组),每组分别灌服生理盐水、500 μg·kg-1 DON、200 μg·kg-1 AFB1和200 μg·kg-1 AFB1+500 μg·kg-1 DON,连续灌服45 d。分别于试验的第0、15、30、45天,每组随机选取6只小鼠,麻醉后处死,取脑组织观察病理变化,并检测脑组织氧化与抗氧化指标及紧密连接蛋白ZO-1和Occludin mRNA的表达量。结果显示,与对照组相比,DON组小鼠脑组织超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性显著下降(P<0.05),NO含量显著升高(P<0.05);AFB1组小鼠脑组织中CAT活性显著下降(P<0.05);AD组脑组织总抗氧化能力(T-AOC)、CAT、SOD活性显著下降(P<0.05),丙二醛(MDA)和NO含量显著上升(P<0.05);各染毒组脑组织ZO-1和Occludin mRNA的表达量显著下降(P<0.05)。研究结果表明,DON与AFB1单一及联合染毒均能造成小鼠脑组织不同程度的病理变化,降低抗氧化性能及紧密连接蛋白ZO-1和Occludin mRNA的表达量,且DON与AFB1的联合毒性大于单一毒性。  相似文献   

6.
The gene Microcephalin (MCPH1) regulates brain size and has evolved under strong positive selection in the human evolutionary lineage. We show that one genetic variant of Microcephalin in modern humans, which arose approximately 37,000 years ago, increased in frequency too rapidly to be compatible with neutral drift. This indicates that it has spread under strong positive selection, although the exact nature of the selection is unknown. The finding that an important brain gene has continued to evolve adaptively in anatomically modern humans suggests the ongoing evolutionary plasticity of the human brain. It also makes Microcephalin an attractive candidate locus for studying the genetics of human variation in brain-related phenotypes.  相似文献   

7.
Identification and location of brain protein 4.1   总被引:8,自引:0,他引:8  
Protein 4.1 is a membrane skeletal protein that converts the low-affinity interaction between spectrin and actin into a high-affinity ternary complex of spectrin, protein 4.1, and actin that is essential to the structural stability of the erythrocyte. Pig brain was shown to contain an 87-kilodalton immunoreactive analog of protein 4.1 that has partial sequence homology with pig erythrocyte protein 4.1 and the same location as spectrin in the cortical cytoplasm of neuronal and glial cell types of the cerebellum.  相似文献   

8.
A selective imidazobenzodiazepine antagonist of ethanol in the rat   总被引:9,自引:0,他引:9  
Ethanol, at pharmacologically relevant concentrations of 20 to 100 mM, stimulates gamma-aminobutyric (GABA) receptor-mediated uptake of 36Cl-labeled chlorine into isolated brain vesicles. One drug that acts at GABA-benzodiazepine receptors, the imidazobenzodiazepine Ro15-4513, has been found to be a potent antagonist of ethanol-stimulated 36Cl- uptake into brain vesicles, but it fails to antagonize either pentobarbital- or muscimol-stimulated 36Cl- uptake. Pretreatment of rats with Ro15-4513 blocks the anticonflict activity of low doses of ethanol (but not pentobarbital) as well as the behavioral intoxication observed with higher doses of ethanol. The effects of Ro15-4513 in antagonizing ethanol-stimulated 36Cl- uptake and behavior are completely blocked by benzodiazepine receptor antagonists. However, other benzodiazepine receptor inverse agonists fail to antagonize the actions of ethanol in vitro or in vivo, suggesting a novel interaction of Ro15-4513 with the GABA receptor-coupled chloride ion channel complex. The identification of a selective benzodiazepine antagonist of ethanol-stimulated 36Cl- uptake in vitro that blocks the anxiolytic and intoxicating actions of ethanol suggests that many of the neuropharmacologic actions of ethanol may be mediated via central GABA receptors.  相似文献   

9.
In our studies on the entry of drugs into the central nervous system we have found the technique of autoradiography combined with radioassay to be a valuable research tool. It has disclosed such unsuspected phenomena as the dual routes of entry into the brain of acetazolamide. Although many factors controlling drug entry remain to be studied, we propose certain general conclusions. 1) The anatomical boundaries of brain are clearly reflected by the penetration and accumulation of all compounds we have studied-a finding that confirms the original proposition that whole-brain homogenates are inadequate for the study of drug and brain relationships. 2) Circulation, expressed as egional blood flow or volume of capillary blood, was seldom decisive in nfluencing entry or accumulation of exogenous substances in the brain. To date, the only compounds demonstrated to be circulation-dependent are trifluoroiodomethane and thiopental. Both are extremely fat-soluble. Tissue binding appears to be an additional factor in the case of thiopental. 3) Penetration is retarded by myelin. All substances we have studied have shown a relatively slower rate of entry into this tissue. In immature brain, before myelinization has taken lace, the primordial white matter is readily penetrated. We have suggested that entry into mature white matter is retarded by the lamellated membranes of the myelin sheath, which should be regarded, therefore, as a component of the blood-brain barrier. The small interstitial space indicated by the limited entry of sulfate ion is an additional hindrance to dispersal of exogenous substances into brain parenchyma. The blood-brain barrier is a complex anatomical, physiological, and biochemical phenomenon, and no unitary hypothesis is adequate to embrace all the observed events. 4) Accumulation of a drug in the brain implies some form of binding or interaction between drug and tissue. Findings on injection of phenobarbital, thiopental, or diphenylhydantoin illustrate such an accumulation. These binding interactions may be nonspecific, as is probable in the case of drugs bound to plasma protein. However, a more fundamental significance is suggested when a drug is found to bind, react with, or accumulate in, a specific anatomical structure of the brain. We have made reference to this possibility in connection with the localization of isonicotinic acid hydrazide or its metabolites in the hippocampus (46), and we have also reported the striking accumulation of acetazolamide in hippocampus, caudate nucleus, and hypothalamus. Although the binding process is poorly understood, further investigation of these phenomena should lead to a clearer understanding of regional variations in brain chemistry. While one should not assume that the demonstration of a focal concentration of a drug implies site of action, correlation between pharmacological action, electrophysiological events, biochemical changes, and temporal and regional drug concentrations may indeed exist (47).  相似文献   

10.
The chlorophenyl groups of DDT and several of its metabolites are capable of participating in a charge-transfer interaction with tetracyanoethylene detectable in the ultraviolet region of the spectrum. In addition, during a change of state DDT undergoes ultraviolet spectral alterations that closely resemble those previously claimed to support the hypothesis suggesting charge-transfer interaction between this pesticide and a component of insect nerve tissue. The pesticide DDT possesses structural characteristics that would permit it to participate in several types of molecular association.  相似文献   

11.
The brain of Homo floresiensis was assessed by comparing a virtual endocast from the type specimen (LB1) with endocasts from great apes, Homo erectus, Homo sapiens, a human pygmy, a human microcephalic, specimen number Sts 5 (Australopithecus africanus), and specimen number WT 17000 (Paranthropus aethiopicus). Morphometric, allometric, and shape data indicate that LB1 is not a microcephalic or pygmy. LB1's brain/body size ratio scales like that of an australopithecine, but its endocast shape resembles that of Homo erectus. LB1 has derived frontal and temporal lobes and a lunate sulcus in a derived position, which are consistent with capabilities for higher cognitive processing.  相似文献   

12.
Sulfonylurea-sensitive adenosine triphosphate (ATP)-regulated potassium (KATP) channels are present in brain cells and play a role in neurosecretion at nerve terminals. KATP channels in substantia nigra, a brain region that shows high sulfonylurea binding, are inactivated by high glucose concentrations and by antidiabetic sulfonylureas and are activated by ATP depletion and anoxia. KATP channel inhibition leads to activation of gamma-aminobutyric acid (GABA) release, whereas KATP channel activation leads to inhibition of GABA release. These channels may be involved in the response of the brain to hyper- and hypoglycemia (in diabetes) and ischemia or anoxia.  相似文献   

13.
依据两种不同的计算输电塔、螺旋锚基础、土体系相互作用的简化计算模型,用有限元原理分析了风荷载作用下计算模型不同时对相互作用下体系可靠度的影响:考虑相互作用时,主要失效路径并无不同,失效概率增大;不同的计算模型对相互作用下的可靠度有影响。  相似文献   

14.
目的观察粒细胞集落刺激因子(G-CSF)对脑挫伤大鼠血清及脑组织中一氧化氮(NO)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量的影响,探讨G-CSF在治疗脑挫伤中的作用.方法将大鼠随机分为治疗组、对照组和正常组,采用自由落体法致SD大鼠脑挫伤动物模型,正常组不致伤.治疗组脑挫伤2h后开始应用G-CSF(浓度为2mg/L)一次性皮下注射50μg/kg治疗.对照组和正常组皮下注射等量生理盐水.给药结束后24h检测治疗组、对照组及正常组大鼠血清及脑组织中NO、MDA和SOD的含量.结果脑挫伤后,对照组大鼠血清及脑组织中NO和MDA含量明显高于正常组,SOD的活性明显低于正常组.治疗组大鼠血清及脑组织中NO和MDA含量明显低于对照组,SOD的活性明显高于对照组.结论G-CSF能有效地提高脑挫伤大鼠血清及脑组织中SOD的活性,降低NO和MDA含量,保护脑组织,改善脑水肿,从而起到了一定的治疗作用.  相似文献   

15.
Turnover of the brain specific protein, S-100   总被引:2,自引:0,他引:2  
Rats were killed after intraventricular administration of [(3)H]leucine, and the turnover rates of total soluble proteins and of the brain specific S-100 protein were determined. The half-life of S-100 was estimated to be 16 days. The S-100 protein, thus, has a turnover not unlike that of the average water-soluble protein of brain.  相似文献   

16.
Extreme gene duplication is a major source of evolutionary novelty. A genome-wide survey of gene copy number variation among human and great ape lineages revealed that the most striking human lineage-specific amplification was due to an unknown gene, MGC8902, which is predicted to encode multiple copies of a protein domain of unknown function (DUF1220). Sequences encoding these domains are virtually all primate-specific, show signs of positive selection, and are increasingly amplified generally as a function of a species' evolutionary proximity to humans, where the greatest number of copies (212) is found. DUF1220 domains are highly expressed in brain regions associated with higher cognitive function, and in brain show neuron-specific expression preferentially in cell bodies and dendrites.  相似文献   

17.
从尼罗罗非鱼的细菌人工染色体基因文库中提取和纯化含有卵巢和脑芳香化酶基因的重组质粒DNA,通过简并PCR制备芳香化酶基因原位杂交探针,并用荧光素进行标记。结果显示,尼罗罗非鱼卵巢和脑芳香化酶基因位于2对不同的小染色体上,而不是位于性染色体上。结果提示:芳香化酶基因不是尼罗罗非鱼主要的性别决定基因。  相似文献   

18.
19.
E L Way  H H Loh  F Shen 《Science (New York, N.Y.)》1968,162(859):1290-1292
Tolerance and physical dependence development to morphine in mice can be prevented by concomitant administration of cycloheximide. The fact that the rate of synthesis of brain 5-hydroxytryptamine (5HT) increases with tolerance to morphine suggests that the protein involved may be associated with 5HT synthesis. Inhibition of this synthesis with p-chlorophenylalanine markedly decreases tolerance and physical dependence development to morphine.  相似文献   

20.
Specific sigma binding sites have been identified in the mammalian brain and lymphoid tissue. In this study, certain gonadal and adrenal steroids, particularly progesterone, were found to inhibit sigma receptor binding in homogenates of brain and spleen. The findings suggest that steroids are naturally occurring ligands for sigma receptors and raise the possibility that these sites mediate some aspects of steroid-induced mental disturbances and alterations in immune functions.  相似文献   

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