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1.
Callus stimulation in distraction osteogenesis   总被引:5,自引:0,他引:5  
Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared.Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the contralateral hemimandible (83 percent versus 49 percent, respectively; p < 0.007). The ratio of cortical to cancellous bone in the distracted callus was uniformly found to be greater in the experimental specimens. The mineral apposition rate was calculated by using fluorescence microscopy and found to be significantly greater in the experimental group both during the period of sequential compression and distraction (3.2 microm/day versus 2.1 microm/day, p = 0.02) and after the period of sequential compression and distraction (1.4 microm/day versus 1.1 microm/day, p = 0.006). Mechanical testing revealed no significant differences in bending strength or stiffness between experimental or control groups (p = 0.54 and 0.47, respectively). This study has demonstrated that daily alternating compression and distraction of 1 mm amplitude during the early consolidation period has a stimulatory impact on callus formation with respect to osteoblastic activity, remodeling, and maturation of bone. Optimal timing and amplitude of sequential movement, long-term biomechanical differences, and molecular pathways have yet to be elucidated.  相似文献   

2.
Zinc homeostasis in the brain is associated with the etiology and manifestation of epileptic seizures. Adult Noda epileptic rats (NER, >12-week-old) exhibit spontaneously generalized tonic-clonic convulsion about once a day. To pursue the involvement of synaptic Zn2+ signal in susceptibility to spontaneous seizures, in the present study, the effect of zinc chelators on epileptogenesis was examined using adult NER. Clioquinol (CQ) and TPEN are lipophilic zinc chelotors, transported into the brain and reduce the levels of synaptic Zn2+. The incidence of tonic-clonic convulsion was markedly increased after i.p. injection of CQ (30–100 mg/kg) and TPEN (1 mg/kg). The basal levels of extracellular Zn2+ measured by ZnAF-2 were decreased before tonic-clonic convulsion was induced with zinc chelators. The hippocampal electroencephalograms during CQ (30 mg/kg)-induced convulsions were similar to those during sound-induced convulsions in NER reported previously. Exocytosis of hippocampal mossy fibers, which was measured with FM4-64, was significantly increased in hippocampal slices from CQ-injected NER that did not show tonic-clonic convulsion yet. These results indicate that the abnormal excitability of mossy fibers is induced prior to epileptic seizures by injection of zinc chelators into NER. The incidence of tonic-clonic convulsion induced with CQ (30 mg/kg) was significantly reduced by co-injection with aminooxyacetic acid (5–10 mg/kg), an anticonvulsant drug enhancing GABAergic activity, which did not affect locomotor activity. The present paper demonstrates that the abnormal excitability in the brain, especially in mossy fibers, which is potentially associated with the insufficient GABAergic neuron activity, may be a factor to reduce the threshold for epileptogenesis in NER.  相似文献   

3.
The purpose of this investigation was to examine the effects of chronic and acute exercise on the main components involved in excitation-contraction coupling and relaxation in rat heart. Sixty male Wistar rats were divided into a sedentary (S) and three 12-wk treadmill-trained groups (T-1, moderate intensity; T-2, high intensity; T-3, interval running). After 12-wk, 15 rats from the S group and 15 rats from the T-2 group were subjected to a single treadmill-exercise session until exhaustion before being killed at 0, 24, or 48 h (acute exercise). The remaining animals were killed 48 h after the last standard exercise session (chronic exercise). The efficacy of the training programs was confirmed by an increase in treadmill endurance time and in skeletal muscle citrate synthase activity. None of the exercise programs modified heart weight or cardiac oxidative capacity. [(3)H]PN200-110 and [(3)H]ryanodine binding to cardiac homogenates indicated that the density of L-type and sarcoplasmic reticulum (SR) Ca(2+) channels was the same in S and trained rats. The SR Ca(2+)-ATPase activity was also unmodified. Finally, the activities of the ectoenzymes Mg(2+)-ATPase and 5'-nucleotidase, which are involved in degradation of extracellular nucleotides, were not affected by either of the running programs. After the acute exercise session, no changes were detected in either of the tested parameters in heart homogenates of S and T-2 animals. We conclude that neither treadmill-exercise training for 12 wk nor exhaustive exercise alters the density of Ca(2+) channels involved in excitation-contraction coupling or the SR Ca(2+)-ATPase and the ectonucleotidase activities in rat heart.  相似文献   

4.
This study examined the effect of 12 weeks of exercise training on daily physical activity in elderly humans. Training consisted of a weekly group session and an individual session with cardio- and weight-stack machines. A group of 15 subjects served as the exercise group [EXER mean age 59 (SD 4) years], and 7 subjects as the controls [CONT mean age 57 (SD 3) years]. Physical activity and physical fitness were measured before the start of training (T), at week 6 and week 12 (T0, T6, T12 respectively) in EXER, and at T0 and T12 in CONT. Physical activity over 14 days was measured using a tri-axial accelerometer and physical fitness was measured during an incremental exercise test. At T12, mean maximal power output had significantly increased in EXER compared to CONT 8 (SD 12) vs -5 (SD 9) W; P < 0.02] and mean submaximal heart rate (at 100 W) had reduced [-10 (SD 7) vs -2 (SD 6) beats x min(-1); P < 0.05]. No differences or changes in physical activity were observed between EXER and CONT. At T6, physical activity on training days was significantly higher than on non-training days (P < 0.001). When the accelerometer output of the training session was subtracted from the accelerometer output on training days, at T12 non-training physical activity was significantly lower than on non-training days (P < 0.004). Accelerometer output of the individual training session at T12 had significantly increased compared to T6 (P < 0.05), whereas, accelerometer output of the group training session had remained unchanged. In conclusion, in elderly subjects an exercise training programme of moderate intensity resulted in an improved physical fitness but had no effect on total daily physical activity. Training activity was compensated for by a decrease in non-training physical activity.  相似文献   

5.
Abstract— The concentrations of several metabolites, including glucose, glycogen, hexose phosphates, adenine nucleotides, amino acids and some tricarboxylic cycle intermediates were estimated in cerebral tissue of rats killed at various stages of pentamethylenetetrazole convulsions. Prior to and during the seizure there was an increase in glycolytic flux and depletion of energy reserves. An accumulation of alanine concomitant with a decreased citrate level observed before the convulsion indicated that a possible interference of pyruvate entry into the tricarboxylic cycle had occurred. At the tonic extensor phase of the seizure and during post-convulsive sedation a small but significant rise in GABA and an attempt to restore some of the labile constituents to more normal values was apparent. The significance of these results in relation to cerebral metabolic control and possible mechanisms of initiation and arrest of the seizure is discussed.  相似文献   

6.
7.
乙酰唑胺对氧惊厥潜伏期的影响   总被引:2,自引:1,他引:1  
Huang JL  Ma YW  Lian QL  Xu JP  Jiang CL  Guo MZ  Sun XJ 《生理学报》2004,56(2):158-162
为探讨脑血流调节与氧惊厥的关系,在复制大鼠氧惊厥模型的基础上,采用行为学方法测定氧惊厥潜伏期,并测定不司部位脑组织氧化与抗氧化指标,采用腹腔注射不同剂量脑血管扩张药物乙酰唑胺,观察脑血管扩张对氧化状态以及氧惊厥潜伏期的影响。观察结果为:(1)与生理盐水组相比,乙酰唑胺200、20 mg/kg体重组腹腔给药后氧惊厥潜伏期(纯氧6 ATA暴露)明显缩短(P<0.01),乙酰唑胺2 mg/kg体重组无明显改变(P>0.05);(2)腹腔给乙酰唑胺(20 mg/kg体重)或生理盐水后,各组各部位脑组织GSH-PX无显著差异(P>0.05),但随暴露时间的延长,其活力呈现先升高后降低的趋势;与对照组相比,乙酰唑胺6min组和生理盐水16min组皮层丙二醛(maleic dialdehyde,MDA)含量均明显增多(P<0.01),乙酰唑胺16 min组海马MDA含量明显增多(P<0.01)。结果表明,乙酰唑胺可缩短氧惊厥潜伏期,加重脑组织氧化损伤。  相似文献   

8.
Febrile convulsion is the most common disorder in childhood with good prognosis. There are different hypotheses about neurotransmitters and trace element changes in biological fluids which can have a role in pathogenesis of febrile convulsion. In this study, serum selenium, zinc, and copper were measured by atomic absorption spectrometry in the children with febrile convulsion (n?=?30) and in the control group (n?=?30). The age and sex of the subjects were registered. Selenium and zinc were found to be significantly lower in febrile convulsion cases than in the control group (p?<?0.0001 and p?<?0.0001, respectively). There was no significant difference in the value of copper between the two groups (p?=?0.16). While selenium and zinc levels were 44.92?±?10.93 μg/l and 66.13?±?18.97 μg/dl in febrile convulsion, they were found to be 62.98?±?9.80 μg/l and 107.87?±?28.79 μg/dl in healthy children. Meanwhile, copper levels were 146.40?±?23.51 μg/dl in the patients and 137.63?±?24.19 μg/dl in the control group, respectively. This study shows that selenium and zinc play an important role in the pathogenesis of febrile convulsion.  相似文献   

9.
Twenty-four college students participated in a single session of electromyographic (EMG) biofeedback in a comparison of three experimental control procedures commonly employed in biofeedback relaxation training research. One group received contingent EMG biofeedback from the forehead area, and each subject in this group served as his or her own control. Subjects in a second group received noncontingent EMG feedback from a tape recorder but were instructed to use the feedback signal to relax their forehead muscles (single blind). Subjects in a third group received the same auditory feedback as those in the second group but were not told the purpose or source of the feedback stimulus (yoked control). The contingent feedback group showed significantly less EMG activity when compared to the other two groups. However, this group did not exhibit significant EMG level decrements from the beginning to end of the session. This seemingly contradictory finding may have been due to statistically capitalizing on the artifactually high EMG level of the experimental and control groups, although the single-blind and yoked-control groups showed nonsignificant increases across the session. The single-blind group's data had a variance several times larger than the other two groups' variance. Findings are discussed with respect to a probing hypothesis as opposed to the previously offered frustration hypothesis. Of the three control procedures, the data suggest the yoked control as the procedure of choice for EMG biofeedback relaxation research.The authors would like to thank David Kazar and Claudia Coleman for their technical assistance with this article.  相似文献   

10.
This study was conducted to elucidate some of the effects of a synthetic progestagen and natural ovarian hormones on spermicidal activity in the sheep vagina. In the first experiment, parous ewes were treated for 17 days either intravaginally with medroxyprogesterone acetate (MAP) or subcutaneously with progesterone. They were inseminated artificially either on the last day of progestagen treatment or during estrus after progestagen withdrawal. Their vulvovaginal junctions were ligated to prevent the loss of sperm cells by drainage to the exterior. Untreated control ewes were inseminated during either estrus or the luteal phase of the estrous cycle. The ewes were killed 22 hr. after insemination, their vaginas flushed, and intact sperm cells and tailless sperm heads counted. In the second and third experiments, some of the ewes were bilaterally ovariectomized and inseminated several weeks later. Other ewes were ovariectomized and given subcutaneous injections of estradiol, progesterone, or both hormones.In the first experiment, most sperm cells were recovered intact from estrous or luteal phase control ewes. The intravaginal administration of MAP increased both the breakage of sperm cells into heads and tails and the disappearance of sperm cells. The spermicidal effects of MAP were just as great in ewes inseminated on the last day of treatment. as in those inseminated during the ensuing estrus; these results indicated that the peak estrogen secretion that occurs near the beginning of estrus was not necessary for the intensification of spermicidal activity.In the second experiment, ovariectomized ewes were compared to estrous and luteal phase ewes in regard to vaginal spermicidal activity. Sperm breakage and disappearance occurred least in estrous ewes, to a somewhat greater degree in luteal phase ewes, and to the greatest extent in ovariectomized ewes. The results suggested that endogenous ovarian hormones, particularly those in estrous ewes, suppress spermicidal mechanisms in the vagina.In the third experiment, the administration of estradiol and progesterone to ovariectomized ewes prevented the increase in sperm cell disappearance. Neither hormone alone prevented the increase.  相似文献   

11.
The immunosuppressive effect of Trypanosoma lewisi infection on alveolar macrophage (AM) activities against Cryptococcus neoformans was studied in an animal model. Two groups of rats were treated with T. lewisi and killed after 4 (4d-rats) and 7 days (7d-rats), respectively. A third group not given T. lewisi, served as control. AM were challenged in vitro with C. neoformans. Phagocytosis was assessed with a fluorescence method. Superoxide anion production was evaluated with the nitroblue tetrazolium (NBT) test. The survival of cryptococci was estimated by counting colony-forming units. The numbers of detached AM from culture plates were determined using a Bürker chamber. The NBT response, adhesion to plate surface and killing activity, but not the phagocytosis of AM from 4d-rats were significantly impaired compared to control or 7d-rats. Thus, T. lewisi causes transitory immunosuppressive effects on AM activities. This rapid T. lewisi immunosuppression model may be useful to study new approaches to anticryptococcal therapy.  相似文献   

12.
Physical activity is known to induce oxidative stress in individuals subjected to intense exercise. Contrarily, there are enzymatic and nonenzymatic defence systems against oxygen radicals in aerobic organisms. Sulphydryl groups such as thiol and glutathione (GSH) can be given as an example to non-enzymatic low molecular weight antioxidants. Carnitine may be related to the performance enhancement in high intensity intermittent exercises and might probably improve the aerobic capacity by stimulating lipid oxidation in muscle cells during long term exercise. But, the effects caused by this supplement during physical activity have not been fully described in the literature. The aim of the study was to compare plasma thiols (PSH), malondialdehyde (MDA) and carnitine levels and maximal oxygen uptake (VO2(max)) of the soccers under regular training with the values of the healthy controls. Our results demonstrates that soccers seem to be under less oxidative stress, as their MDA levels were significantly lower (P < 0.001) when compared with the control group while their PSH levels were significantly elevated (P < 0.001), during resting condition. In addition, the plasma carnitine concentrations of the soccer group yields lower values while the VO2(max) yields a higher value when compared with the control group. The differences between the soccer and the control groups are significant (for both, P < 0.001). The present research reveals the fact that regular soccer training shows beneficial effect on decreasing of lipid peroxidation levels. Furthermore; the sportsmen who are under intense training programs have low plasma carnitine values which do not cause negative effect on their sportive performance.  相似文献   

13.
Osteoporosis-related fractures are one of the complications of Graves’ disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves’ disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves’ disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves’ disease.  相似文献   

14.
慢性镉负荷雄性大鼠的睾丸及生殖内分泌功能活动   总被引:18,自引:0,他引:18  
Chen L  Ren WH  Zhu SL  Gao W  Zhou J  Jiang YZ  Gu Y 《生理学报》2002,54(3):258-262
选择健康SD雄性成年大鼠60只,随机分成对照组(C组)、镉负荷中剂量组(M组)和镉负荷高剂量组(H组),每天分别饲喂含镉0,5,10mg/kg的大鼠全价饲料,连续6周,研究了镉负荷对大鼠睾丸及生殖内分泌功能活动的影响。结果显示:在整个实验期内,M和H组大鼠睾丸组织中的镉含量极明显上升,锌含量销有下降,与对照组差异不显著;血浆镉、锌含量虽分别表现稍有升高和下降,但与对照组比较无明显差异;H组睾丸精子头计数和每日精子生成量在镉负荷第3周极显著下降,第6周时,M和H组均极明显低于对照组;在整个实验期内,H组大鼠ALP活明显低于C组;LDH-X活性在M和H组大鼠均极明显低于C组;M和H组血浆T水平下降,均低于或显著低于C组;3组间的FSH和LH水平无明显差异。结果提示:慢性镉负荷在睾丸组织中逐步蓄积可引起睾丸一些酶活性改变、精子生成减少及内分泌功能活动低下。  相似文献   

15.
One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage.  相似文献   

16.
The effects of electroconvulsive shock on the levels of acetylcholinesterase in several brain regions of the rat were studied. Hippocampus, mesencephalon, cortex, and striatum exhibited rapid changes in acetylcholinesterase activity during the first few minutes following the convulsion, whereas brainstem and basal forebrain levels remained unchanged. In both hippocampus and midbrain there was a sustained decrease in activity: the total acetylcholinesterase activity was decreased by up to 40% within 2 min of the convulsion and did not return to control values for another 3 h. Thirty minutes after a flurothyl-induced convulsion there was a similar fall in acetylcholinesterase activity in both these regions, whereas a subconvulsive electric shock produced no change. It is concluded that a convulsion produces significant short-term decreases in acetylcholinesterase activity in areas of the rat brain that are involved in the generation and propagation of seizures, and the question is raised of whether this is related to the increase in seizure threshold that follows a convulsion.  相似文献   

17.
Obesity is a multifactorial disease developing following impairment of the energy balance. The endocrine system is known to be affected by the condition. Serum thyroid hormones and trace element levels have been shown to be affected in obese children. Changes in serum thyroid hormones may result from alterations occurring in serum trace element levels. The aim of this study was to evaluate whether or not changes in serum thyroid hormone levels in children with exogenous obesity are associated with changes in trace element levels. Eighty-five children diagnosed with exogenous obesity constituted the study group, and 24 age- and sex-matched healthy children made up the control group. Serum thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (TG), selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn) levels in the study group were measured before and at the third and sixth months of treatment, and once only in the control group. Pretreatment fT4 levels in the study group rose significantly by the sixth month (p?=?0.006). Zn levels in the patient group were significantly low compared to the control group (p?=?0.009). Mn and Se levels in the obese children before and at the third and sixth months of treatment were significantly higher than those of the control group (p?=?0.001, p?=?0.001). In conclusion, fT4, Zn, Cu, Mn, and Se levels are significantly affected in children diagnosed with exogenous obesity. The change in serum fT4 levels is not associated with changes in trace element concentrations.  相似文献   

18.
【目的】探索农田重金属Cd~(2+)和Ni~(2+)污染对植食性昆虫求偶行为潜在的影响。【方法】在人工饲料中添加不同类型的重金属,设置成Cd~(2+)、Ni~(2+)、Cd~(2+)-Ni~(2+)和空白对照(CK)4个处理,重金属浓度均为5 mg/kg。实验室条件下饲养亚洲玉米螟Ostrinia furnacalis(Guenée)初孵幼虫,系统观察其各代存活雌蛾求偶行为。【结果】重金属Cd~(2+)和Ni~(2+)对亚洲玉米螟3代存活雌蛾求偶百分率、求偶高峰期出现的时间及求偶持续时间都产生了影响。其中第2代求偶百分率与对照组差距最大,第3代受到的影响最小,甚至表现出促进作用;各重金属处理的求偶高峰期出现的时间仅在第2代与对照组保持一致外,第1代、第3代均发生改变;存活雌蛾求偶平均持续时间随着重金属饲养亚洲玉米螟代数的增加而逐代减少。与对照组各代各暗期最长求偶持续时间为4.89 h相比,重金属处理的雌蛾平均求偶持续时间最大值出现在Ni~(2+)处理第1代的第3个暗期,值为5.56 h;最小值为Cd~(2+)处理的第2代的第2、第3个暗期,值均为3.08 h。【结论】重金属Cd~(2+)和Ni~(2+)对亚洲玉米螟存活雌蛾的求偶行为产生了影响。  相似文献   

19.
This study was designed to investigate the protective effect of CD4+CD25+ regulatory T cells (Tregs) against zona pellucida glycoprotein 3 peptide (pZP3) immunization‐induced premature ovarian insufficiency (POI) in mice. A mouse POI model was induced by two subcutaneous injections of pZP3 (50 nmol/L). Mice in the pZP3‐Treg group were intraperitoneally injected with 5 × 105 CD4+CD25+ Tregs after the POI model was established. Sex hormone levels, follicle numbers, apoptotic events, and the Akt/FOXO3a signaling pathway molecules in the ovaries were assessed. Compared with control group, the weight of ovaries in both pZP3 group and pZP3‐Treg group was decreased and no difference was found between them. The number of follicles in the Treg transferred mice, like in pZP3 group, was significantly reduced compared to the control group, but showed a modest improvement when compared the pZP3 group alone. Significantly lower serum concentrations of follicle‐stimulating hormone, luteinizing hormone, and anti‐zona pellucida antibodies (AZPAbs) were found, while the concentrations of estradiol and anti‐Mullerian hormone increased. In mechanism, Treg cell transfer to ZP3 treated mice restored the levels of Caspase3 to control levels, and partially restored Bax, however, had no effect on Bcl‐2. Moreover, Treg cell transfer to ZP3 treated mice partially restored the levels of Akt and FOXO3a, and partially restored the ratios of p‐Akt/Akt and p‐FOXO3a/FOXO3a. In conclusion, Treg cells improved some aspects of ZP3‐induced POI which may be mediate by suppressing ovarian cells apoptosis and involving the Akt/FOXO3a signaling pathway. Therefore, Treg cells may be protective against autoimmune POI.  相似文献   

20.
Exploratory locomotor activity was studied in the experiments on adult male mice. It was shown that routine nootropic drugs as well as newly synthesized nootropic compounds were able to facilitate the development of inhibition during one registration session. Inhibition may be used for revealing only selective nootropic drugs devoid of sedative and stimulating effects.  相似文献   

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