Hippocampal EEG responses induced by carbachol and atropine infusions into the septum and the hippocampus in the urethane-anaesthetized rat

Infusion of 1 μg of carbachol, a potent cholinergic agonist, into the lateral septum of the urethane-anaesthetized rat systematically caused the induction of clear-cut hippocampal theta (θ). However, infusion of an equivalent amount of the drug into the hippocampus, close to the recording electrode, failed to induce θ in 50% of the animals and produced a mixture of θ waves and desynchronized activity, resulting in atypical EEG patterns, in the remaining subjects. Both carbachol EEG effects were blocked by intraseptal infusion of the antimuscarinic agent, atropine. Our data demontrate that muscarinic receptors in the septum are predominent sites for cholinergic agonist-antagonist action capable of generating or suppressing hippocampal θ in the rat. They also indicate that intraseptal cholinergic mechanisms play an important role in the initiation and generation of this rhythm.     

风湿性心脏病二尖瓣置换术中细胞因子水平的变化

目的测定风湿性心脏病二尖瓣置换术中细胞因子水平,了解它们的变化规律。方法 11例体外循环(CPB)下二尖瓣置换术患者,分别于术前,主动脉阻断前,主动脉阻断后5min,主动脉开放后10min、1h、2h、4h、24h测定白介素6(IL-6)、白介素8(IL-8)、白介素10(IL-10)以及肿瘤坏死因子(TNF)。结果IL-6、IL-8、IL-10水平在CPB开始后逐渐升高,在主动脉开放后2h左右达到高峰(P<0.01)。之后逐渐下降,到主动脉开放后24h已显著下降。TNF水平在CPB开始后逐渐升高,在主动脉开放后24h仍维持在很高的水平(P<0.01)。结论CPB下二尖瓣置换术中既有促炎因子水平的升高,又有抗炎因子的激活。     

Neutrophil superoxide release and interleukin 8 in acute myocardial infarction: distinction between complicated and uncomplicated states

Superoxide release in neutrophils and sera levels of interleukin 8 (IL-8) were determined in 15 patients with complicated acute myocardial infarction (MI) and 15 patients with uncomplicated MI. All patients showed increased superoxide release in unstimulated and stimulated neutrophils compared with healthy control subjects, indicating priming of these cells. Superoxide release of unstimulated or stimulated neutrophils was found to be significantly higher in patients with complicated MI than in patients with uncomplicated MI. Thrombolytic therapy did not affect the rates of superoxide release. The neutrophil chemoattractant/activator IL-8 was detected in the sera of all patients, with significantly higher levels in those with complicated MI. The highest levels of IL-8 were detected at admission to the Coronary Care Unit and significantly decreased thereafter, suggesting its contribution to neutrophil-mediated tissue injury. The high levels of IL-8 may be one of the major contributors to the priming of neutrophils in these patients.     

The effects of A 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635

The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT_1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin (TTX), 60 mM K⁺ and perfusion with Ca²⁺-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT_1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT_1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT_1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT_1A receptors. Received: 11 September 1996 / Accepted: 25 November 1996     

Identification of neutrophil chemotactie factors in bronchoalveolar lavage fluid of asthmatic patients

Background Although neutrophils have been implicated in bronchial asthma, the mechanism(s) which bring these cells into the airways is poorly understood. Objective To investigate the presence and identity of neutrophil chemotactic factors in bronchoalveolar lavage (BAL) fluid from atopic asthmatic subjects. Method BAL fluid was obtained from 13 subjects (seven asthmatics and six normals). aged 19 to 60 yr, at bronchoscopy. Separation of neutrophil chemotactic activity (NCA) was achieved by FPLC cation exchange chromatography. Fractions were collected and assayed for chemotaxis multiwell micro-chemotaxes chambers using polycarbonate filters, for the complement peptide C5a/C5a des Arg by radioimmunoassay (RIA) and for interleukin-8 (IL-8) by ELISA. Results NCA was found in FPLC fractions of BAL samples in four out of seven asthmatics and each of these subjects had at least three similar peaks of NCA. The major peak of NCA was found to contain immunoreactive C5a/C5a des Arg and chemotaxis. In response to this NCA could be blocked by desensitization of the neutrophils with recombinant C5a. Purified serum derived C5a/C5a des Arg was found to have altered chromatographic properties when added to BAL fluid; this suggested that BAL fluid contained proteins which interacted with the C5a/C5a des Arg. Immunoreactive IL-8 (iIL-8) was also detected but its concentration or chemical form was insufficient to induce neutropbil chemotaxis. Conclusion This study demonstrates that bronchial asthmatic lavage fluid contains C5a/C5a des/Arg and iL-8, together with other as yet unidentified factors which may contribute to neutropbil recruitment in this disease.     

局灶性脑缺血对细胞周期蛋白D1/CDK4基因表达的影响

目的观察脑缺血后细胞周期蛋白（cyclin）D1和它的酶CDK4基因表达，以及这种表达的改变是否影响神经细胞凋亡。方法成年雄性SD大鼠32只随机分为假手术组（n=4）和实验组（n=28），实验组再进一步分为7个亚组（再灌注2h，6h，12h，1d，3d，7d和14d，每组n=4）。应用线栓法建立SD大鼠大脑中动脉阻塞／再灌注模型．TUNEL法检测神经细胞凋亡。原位杂交检测cyclinD1和CDK4mRNA的表达。结果CyclinD1mRNA和CDK4mRNA的表达与凋亡细胞的区域基本相同。再灌注2h脑组织即开始出现神经细胞凋亡，并于1d分别在皮层区和纹状体区达高峰（分别为72．80±4．66和87．75±0．85）。神经细胞cyclinD1mRNA和CDK4mRNA的表达分别于再灌注2h和6h开始逐渐增强，并于12h和1d达高峰（皮质区分别为94．50±2．75和85．75±3．73，纹状体区分别为88．25±5．06和89．80±2．93）。结论CyclinD1和CDK4选择性地在形态学完整或已经有改变的缺血侧神经元和少突胶质细胞内表达。CyclinD1／CD1（4mRNA表达可能是诱导细胞凋亡的重要因素之一。     

Two selective 5-HT1A receptor antagonists, WAY-100 635 and NDL-249, stimulate locomotion in rats acclimatised to their environment and alter their behaviour: a behavioural analysis

The aim was to study firstly, the motor effects of a new 5-HT_1A antagonist, NDL-249 [(R)-3-(N-cyclopentyl-N-propylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrochloride] and of the reference 5-HT_1A antagonist WAY-100 635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride], in comparison to the 5-HT_1A agonist (±)-8-OH-DPAT [(8-hydroxy-2-(di-N-propylamino) tetralin, hereafter 8-OH-DPAT], in rats acclimatised to the automated activity cages; secondly, to study whether the behavioural effects of NDL-249 and 8-OH-DPAT are sensitive to the 5-HT depleting effects of p-chlorophenylalanine (PCPA); thirdly, to characterise the nature of the antagonist-induced activation seen in the automatic activity cages with the aid of a behavioural observation analysis; fourthly, to examine the interaction between the 5-HT_1Areceptors mediating the behavioural effects and dopamine (DA) receptors. NDL-249 was found to bind in vitro to rat hippocampal 5-HT_1A receptors with high affinity and selectivity. In second messenger studies, it was devoid of agonist-like effects. In the locomotor activity studies, each antagonist significantly increased the incidence of horizontal activity, peripheral activity and rearing. 8-OH-DPAT, while significantly increasing peripheral and horizontal activities, decreased the incidence of rearing. PCPA blocked the motor effects of NDL-249 but did not affect those of 8-OH-DPAT. Observational analyses indicated that NDL-249 induced significant increases at one or more doses in sniffing, rearing and locomotion together with a significant reduction in stillness. WAY-100 635 significantly increased the incidence of rearing, intense grooming and vacuous chewing. The significant increases in sniffing, grooming and intense grooming and the significant decrease in stillness induced by the DA D₁ agonist, SK&F 38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride], were not altered by concomitant pre-treatment with NDL-249. Pre-treatment of rats with either the DA D₁ antagonist SCH-23390 (2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) or the DA D₂ antagonist, raclopride, blocked the reduced stillness and increased sniffing and rearing induced by NDL-249. In conclusion, 5-HT_1A antagonists including the new selective antagonist, NDL-249, induce mild behavioural activation in rats, which is mediated probably indirectly via DA systems. Received: 3 April 1997/Final version: 23 February 1998     

Behavioural specificity of 8-OH-DPAT-induced feeding

8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) has been reported to increase food intake. This effect was confirmed in rats consuming plain or sweetened wet mash. However, the consumption of a 35% sucrose solution or of a range of other flavoured liquids was enhanced marginally if at all by a single low dose of 8-OH-DPAT, and the drug actually decreased the consumption of a high protein liquid diet. 8-OH-DPAT did, however, increase gnawing on a wooden block. These results suggest that 8-OH-DPAT-induced hyperphagia may to some extent be secondary to the elicitation of chewing behaviour. 8-OH-DPAT also caused certain other behavioural changes, including a suppression of grooming.     

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase α monoclonal antibodies,bromodeoxyuridine labeling,and nucleolar organizer region counts

Summary The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P<0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P<0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P<0.005). These results suggest that the Ki-67 and DNA polymerase PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.Supported by grants CA-13525 and CA-50210 from the National Cancer Institute, by a grant from the Phi Beta Psi Sorority, and by Grant-in-Aid A 63771083 from the Ministry of Education, Science, and Culture of Japan     

The reduction of water intake in rats caused by a low dose of apomorphine is unaltered by α-methyl-p-tyrosine: are autoreceptors not involved?

Summary Low doses of the dopamine (DA) agonist apomorphine (APO) induces a behavioural syndrome characterized by reduced spontaneous activity, reduced food and water intake and induction of yawning and penile erections. Traditionally these effects of APO have been considered to be caused by a preferential stimulation of DA autoreceptors, causing a decreased amount of transmitter at the postsynaptic receptors. If this is so, it could be hypothesized that 1) the same behavioural effects should be obtained if DA transmission is decreased by some other means, for example by synthesis inhibition, and that 2) the response to APO should be altered if DA transmission is already lowered.It was found that high doses of -methyl-p-tyrosine (-MPT; 50–200 mg/ kg) did not reduce water intake in thirsty rats, which low doses of APO do. It was further found that pretreatment with -MPT did not alter the response to APO. These results are difficult to reconcile with the DA autoreceptor hypothesis claiming that behavioural effects of low doses of APO are caused by a decreased release of DA. An alternative interpretation is that low doses of APO stimulates a certain population of sensitive postsynaptic D-2 receptors.