Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

Modification of the noradrenergic cyclic AMP generating system in the rat limbic forebrain by amphetamine: Role of its hydroxylated metabolites

Summary The cyclic AMP responses to norepinephrine (NE) in slices of the rat limbic forebrain after the administration of (S)-amphetamine and the role of its para- and -hydroxylated metabolites were investigated. The chronic but not acute administration of (S)-amphetamine to rats causes a significant reduction in the sensitivity of the cyclic AMP generating system to NE without changing the basal level of the nucleotide. This change in the sensitivity of the system is not associated with a change in the EC₅₀ value for NE but reflects mainly a decrease in the maximal response. After withdrawal of the drug, the cyclic AMP response to NE returned to control values within 4 days. In vitro, (S)-p-hydroxyamphetamine (POH) and all stereoisomers of p-hydroxynorephedrine (PHN) except (S,R)-PHN enhanced the cyclic AMP response to low concentrations of NE. Since (S,R)-PHN [like the other stereoisomers of PHN and (S)-POH] inhibited in a dose-dependent manner the high affinity uptake of ³H-NE into crude synaptosomal fractions of the limbic forebrain, the results might suggest that the presumably physiological enantiomer of PHN also exerts receptor blocking properties. The inhibition by (S,R)-PHN of the cocaine induced potentiation of the cyclic AMP response to NE supports this supposition. The results provide evidence that the hydroxylated metabolites of (S)-amphetamine, (S)-POH and (S,R)-PHN, modify the action of the parent drug on central noradrenergic function at the level of the NE receptor coupled adenylate cyclase system.     

In vitro expression of inducible nitric oxide synthase in the nasal mucosa of guinea pigs after incubation with lipopolysaccharides or cytokines

In order to demonstrate the involvement of nitric oxide synthases (NOS) – in particular the inducible isoform (iNOS) – in inflammatory processes within the nasal airways, we used organ-bath incubation to study isolated inferior turbinates and mucosa of the maxillary sinus of guinea pigs. The pattern of the expression in various substructures of the nasal mucosa was of special interest. Mucosa was incubated for 6 h with lipopolysaccharides (LPS) produced by E. coli, interleukin II (IL-2) or tumor necrosis factor-alpha (TNF-α). Saline was used as the control solution. Following incubation the specimens were fixed in buffered 4% formaldehyde solution over a period of 4 h. Tissues were next exposed to nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase-reaction and immunostained with specific antibodies to iNOS. Results then showed a clearly increased or initiated expression of iNOS in epithelium, glands, leucocytes and blood vessels of treated tissues in comparison to the control specimens. The inflammatory mediator LPS and the cytokines Il-2 or TNF-α alone were found to be capable of increasing the expression of iNOS, although the effects of LPS clearly exceeded those of the cytokines. This finding implicates iNOS-generated nitric oxide as a key factor for causing nasal swelling, secretion and obstruction during nasal infections and allergic episodes. Received: 18 November 1997 / Accepted: 22 April 1998     

听力正常成年人同时多频听觉稳态诱发反应研究

目的　了解正常听力成人同时多频听觉稳态诱发反应的特性。方法　 32名受试者 (6 4耳 ) ,年龄 2 2～ 32岁 ,平均 2 8.3岁 ,男 12名 ,女 2 0名 ,双耳纯音听阈测试各频率听阈在 2 0dB以内。以载波频率为 0 .5、1、2和 4kHz的纯音 ,调制频率分别为 77、85、93和 10 1Hz(左耳 )以及 79、87、95、10 3Hz(右耳 )的调幅声作为测试信号 ,双耳 8个频率同时给声刺激 ,同时自动判定并记录反应。各载波频率的阈值、反应幅度等数据采用SPSS统计软件分析。结果　①同时多频听觉稳态诱发反应阈高于纯音听阈 7～ 19dB。②反应阈经双因素方差分析 (侧别×频率 ) ,左右耳之间无显著性差异 (F =1.94 2 ;μ 1,179;P =0 .16 5 ) ,但各频率之间有显著性差异 (F =31.2 5 4 ;μ 3,179;P =0 .0 0 0 ) ,各频率反应阈均值之间进一步的两两比较显示 0 .5kHz反应阈与其它频率之间存在显著性差异。③以 6 0dBSPL作为分析强度 ,男女受试者在各个频率的反应幅度的差异经双因素方差分析 (性别×频率 )有显著性差异 (F =2 .94 8;μ 3,175 ;P =0 .0 34) ,0 .5kHz反应幅度最低 ,4kHz最高。性别之间有显著性差异 (F =16 .4 90 ;μ 1,175 ;P=0 .0 0 0 ) ,男性反应幅度高于女性。④各频率不同状态下背景噪声的差异经双因素方差分析 ,提示清醒状     

不同麻醉诱导下小儿气管插管时的心血管应激反应

目的用随机对照前瞻性研究方法,比较小儿气管插管时心血管反应,评价不同麻醉诱导方式对插管时应激反应的抑制作用.方法68例1～6岁的患儿被随机分成P、PF及PFI组,P组静脉注射硫喷妥钠5 mg/kg;PF组先静脉注射芬太尼3 μg/kg,再静脉注射硫喷妥钠5 mg/kg;PFI组先静脉注射芬太尼3μg/kg,再静脉注射硫喷妥钠5 mg/kg,同时吸入3%异氟醚.所有患儿由同一位医师进行气管插管,记录其麻醉前以及插管前后的心率和血压.结果插管后P组的心率和血压最高,不仅显著高于插管前,还显著高于基础值（P＜0.05）.PF组插管后的心率和血压虽然也高于插管前,但低于P组,而且与基础值比较没有显著性差异.PFI组插管后的血压仅略高于插管前,但比基础值低（P＜0.05）,在3组中最低（P＜0.05）,且升幅最小（P＜0.05）,其收缩压和舒张压的升幅分别为11%和26%.结论给患儿插管时联合应用硫喷妥钠、芬太尼和异氟醚,心血管反应最小,提示其可以较好地抑制插管所至的应激反应.     

光导纤维支气管镜经口和经鼻气管插管患儿心血管反应的比较

目的比较小儿光导纤维支气管镜(FOB)经口和经鼻气管插管的心血管反应。方法选择美国麻醉医师协会(ASA)身体状态分级为Ⅰ级、在全身麻醉下施择期整形外科手术的患儿65例,随机分为经口组(n=36)和经鼻组(n=29)。在常规静脉麻醉诱导后实施FOB气管插管。测定麻醉诱导前(基础值)、后,气管插管时和气管插管后5 min内(测定间隔为1 min)血压(BP)和心率(HR),记录气管插管时间。结果经鼻组气管插管时间显著长于经口组(P<0.05)。FOB气管插管导致两组BP和HR均比麻醉诱导前基础值显著升高(P均<0.05)。与经口组相比,气管插管致BP增高和HR增快反应在经鼻组较轻,持续时间较短。经口组气管插管时BP和HR及观察过程中BP和HR最大值均显著高于经鼻组(P均<0.05)。结论FOB经口和经鼻气管插管均可引起小儿BP和HR显著升高,但FOB经鼻气管插管时心血管反应较FOB经口气管插管时轻。     

Neurocognitive function in antisocial personality disorder

Recent neuroimaging studies and neuropsychological test findings support the contention that prefrontal dysfunction is associated with psychopathic personality traits and antisocial behavior. However, conflicting results have arisen regarding performance on measures of frontal executive function. We administered a neuropsychological test battery consisting of measures sensitive to frontal lobe dysfunction and a battery of personality questionnaires and clinical scales sensitive to antisocial personality disorder (APD) subjects presenting with prominent psychopathic personality features and matched control subjects. We also monitored the subjects’ electrodermal activity during the presentation of emotionally charged stimuli. APD subjects showed greater neuropsychological deficits on measures sensitive to orbitofrontal dysfunction in comparison to control participants. Moreover, APD subjects were electrodermally hyporesponsive to aversive stimuli relative to control group members. APD subjects did not demonstrate performance deficits on classical tests of frontal executive function. Participants also underwent clinical assessment. As expected, APD subjects were less conscientious, self-reproaching, guilt-prone, and socially anxious than matched control subjects. Moreover, the scores indicated that APD subjects were more venturesome and uninhibited relative to control subjects. Contrary to expectations, APD subjects and community control subjects did not differ on a self-report measure of sensitivity to specific phobic situations.     

IL-10与可溶性鸡Ⅱ型胶原对实验性关节炎的联合治疗作用

目的 :考察重组人白细胞介素 10 (rhIL 10 )对可溶性鸡Ⅱ型胶原 (SCCⅡ )治疗大鼠佐剂性关节炎(AA)疗效的影响。方法 :通过测量足肿胀度、体重、胸腺与脾脏系数 ,观察不同部位淋巴细胞ConA增殖反应并检测腹腔巨噬细胞 (PMΦ)与滑膜组织细胞(SMCs)产生IL 1的水平。结果 :与SCCⅡ(0 .0 3mg·kg-1·d-1,ig)或IL 10 (1,2 μg·d-1,sc)单独治疗比较 ,二者联合治疗大鼠AA ,明显改善上述观察指标 ,同时使SCCⅡ的口服耐受诱导期缩短 ,增强了治疗效果。结论 :IL 10能提高SCCⅡ治疗大鼠AA的治疗效果。     

Toxicity assessment of environmental pollutant phenanthrene in clam Venerupis philippinarum using oxidative stress biomarkers

The objective of this study was to assess potential toxic effects of phenanthrene (PHE) on tissues of clam Venerupis philippinarum using parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), and glutathione (GSH), as well as DNA damage and lipid peroxidation (LPO) in gills and digestive glands of V. philippinarum, were analyzed after a 1-, 3-, 6-, 10- and 15-day exposure to seawater containing PHE at concentrations of 2, 10, 50 μg/L. The results showed that the activity of most antioxidant enzymes was induced throughout the exposure period, and different trends were detected with time of exposure. The oxidative stress could be obviously caused in the gills and digestive glands under the experimental conditions. Overall, our results show that digestive glands are more sensitive to marine environmental stressors than gills, and GSH is proposed as potential useful biomarker as it showed good correlation with the target contaminant. This could provide useful information for toxic risk assessment of environmental pollutant PHE.     

Intra and intersubject variability in auditory steady-state response amplitude with high modulation rates to 1000 Hz amplitude modulated and tone pip stimuli

Abstract

Objective: This study set out to provide further information on how high modulation/stimulus rates affect the auditory steady-state response (ASSR) amplitude for a 1000-Hz tone, and how this effect varies between individuals. Both sinusoidal amplitude modulated tones and tone pip stimuli were investigated. Design: Modulation/stimulus rates were 70, 80, and 90 Hz and the peak to peak stimulus levels were matched for the two different types of stimuli, at 90.5 dBSPLppe. Study sample: The study was carried out on fourteen normally-hearing adults (9 males and 5 females) Results: Overall the ASSR amplitude to the two types of stimuli was similar. In general there was an increasing response amplitude between rates of 70 and 90 Hz; The relationship between the amplitude of the response and the modulation /stimulus rate varied considerably between subjects. Conclusions: Optimum stimulus rates based on group data may not give the best rate in a significant proportion of subjects. Currently tone pip ABR is the primary method used in assessing hearing in babies. Finding a way of avoiding suboptimal stimulus rates for ‘80-Hz’ ASSR in babies will improve the likelihood of ASSR being seen as an alternative.