柳珊瑚酸促进抗利尿释放而引起大鼠水潴留

目的：了解柳珊瑚酸抗利尿作用的机制。方法：清醒大鼠给予水负荷后ｉｇ Ｓｕｂ ３．１６ｍｇ．ｋｇ＾－１,收集尿液,用原子发射光谱仪测定尿离子的总排出量;放射免疫法测尿ＰＧＥ以及血浆ＰＧＥ,ＡＤＨ和醛固酮水平。结果：给药后２４ｈ内,Ｓｕｂ减少正常大鼠的累积尿量以及钠和钾的总排出量,此作用随时间逐渐减弱,并可因大鼠去垂体而几乎完全消失,但不受去肾上腺影响。     

柳珊瑚酸与N-环己基柳珊瑚酰胺对大鼠和猫尿量、呼吸和血压的影响(英文)

目的:比较柳珊瑚酸(suberogorgin,Sub)与N-环己基柳珊瑚酰胺(N-cyclohexyl suberogorgamide,N-CS)的药理作用。方法:大鼠和麻醉猫给予水负荷和Sub或N-CS后记录其尿量,并测定尿Na~ ,K~ 浓度;猫实验中Sub和N-CS采用等毒性剂量(1/50 LD_(50))。结果:Sub 0.4 mg·kg(-1)和N-CS 1.5mg·kg~(-1)iv分别使猫尿量减少63％和增加25％,这种作用维持9h以上。Sub和N-CS均明显提高猫呼吸频率和潮气量,但对血压无明显影响。Sub 1.3mg·kg~(-1)和N-CS 3.2mg·kg~(-1)ip分别使大鼠尿量减少48％和增加14％,并有明显的排Na~ ,K~ 作用。结论:Sub具抗利尿作用而N-CS却具利尿利用。     

柳珊瑚酸对乙酰胆碱酯酶的抑制作用(英文)

目的:研究柳珊瑚酸(suberogorgin,Sub)抗乙酰胆碱酯酶(AChE)作用的选择性、可逆性和动力学。方法:制备大鼠和人红细胞膜、大鼠脑和蚯蚓背肌提取液作为AChE组织样品,人血浆为丁酰胆碱酯酶(BuChE)样品;比色法测酶活力。结果:Sub明显抑制上述样品的AChE活力,其pl_(50)各为4.03,4.92,3.82和4.67,对BuChE无抑制作用。Sub与AChE一起孵温后,酶活力在3min内降至最低,而且离心洗涤可使酶活力恢复。不同浓度的Sub对AChE抑制作用的动力学曲线为平行线。结论:Sub是选择性和可逆性的AChE抑制剂,它与AChE的结合点在AChE的外周阴离子部位。     

南海小月柳珊瑚中倍半萜类化学成分研究(英文)

对南海小月柳珊瑚Menellasp.的化学成分进行研究。应用反复硅胶柱层析、Sephadex LH-20柱色谱和制备薄层等多种色谱方法进行分离和纯化。从中分离得到3个subergorane倍半萜和1个suberosane倍半萜化合物,利用波谱分析技术和文献比对等方法确定化合物的结构,分别为柳珊瑚酸(1),柳珊瑚酸甲酯(2),2β-羟基柳珊瑚酸甲酯(3)和suberosenol A(4)。以上化合物均为首次从小月柳珊瑚属(Menella)中分离得到。     

柳珊瑚酸钠对豚鼠离体工作心脏及其缺血再灌注血流动力学的影响(英文)

目的:研究柳珊瑚酸钠(suberogorgin,Sub)对正常和缺血再灌注损伤工作心脏的作用.方法:用含edetic acid 0.2 μmol·L~(-1)的克-亨氏液(37±0.5 C)从左肺静脉对心脏进行灌注.左房灌注压和左室负荷分别为1.0和7.2kPa,50 min低流缺血期间,冠脉流量为正常灌注时的4.7±0.2％,此后进行35 min的再灌注.结果:Sub 10 μmol·L~(-1)使正常工作心脏的AP,LVSP, dp/dt_(max),-dp/dt_(max),CO和SV分别提高14％,17％,17％,22％,15％和32％,但使LVEDP和HR各下降200％和11％;Sub 50 μmol·L~(-1)则降低上述指标.对于缺血再灌注损伤的心脏,Sub 10 μmol·L-1使除HR外的上述指标恢复至缺血前水平,而Sub 50 μmol·L~(-1)仅使这些指标部分恢复.结论:Sub对心肌缺血再灌注损伤有明显的保护作用.     

凝血酶引起大鼠血小板神经肽Y释放的机制(英文)

目的:研究凝血酶引起血小板释放NPY的作用及其机制.方法:用血小板聚集仪记录凝血酶及ADP引起的血小板聚集;用放射免疫法测定血小板及血浆中的NPY;用Fura 2荧光测定法记录细胞内游离ca~(2 )([Ca~(2 )]_i). 结果:凝血酶在引起NPY释放的同时,细胞内游离钙([Ca~(2 )]_i)升高.依地酸基本消除凝血酶引起的[Ca~(2 )]_i增高,并显著减少凝血酶引起的NPY释放.维拉帕米对凝血酶的作用无显著影响.磷酸肌酸与磷酸肌酸激酶合用或消炎痛均可使凝血酶引起的NPY释放减少. 结论:凝血酶引起的血小板NPY释放与(1)细胞外ca~(2 )通过非电压依赖性钙通道进入及(2)花生四烯酸代谢物和ADP释放的正反馈机制有关.     

甘草次酸钠对大鼠化学性腹膜炎的影响(英文)

目的:研究甘草次酸钠(SG)的抗炎机制.方法: 制备大鼠腹膜炎模型,用放免法测PGE_2含量,Folin-酚试剂法测蛋白含量,邻苯三酚-NBT法测SOD活性,竞争性蛋白结合法测cAMP含量.结果:组胺致炎时,SG 10-20 mg·kg~(-1) im减少渗液量;角叉菜胶致炎时,SG 20 mg·kg~(-1) im使渗液量及其中PGF_2含量减少,SOD活性增加;花生四烯酸致炎时,SG 20 mg·kg~(-1)im抑制Neu中cAMP浓度下降,减少渗出液中PGE_2含量.SG也使三种腹膜炎渗出液中Neu计数和蛋白含量减少.结论:SG通过抑制Neu游走及PGE_2合成、降低毛细血管通透性、清除氧自由基而发挥抗炎作用.     

Inhibition of prostaglandin synthesis in brain of rat by dexamethasone: Lack of effect of dexamethasone phosphate ester and various hormonal steroids

The present study was designed in order to characterize the inhibitory effect of dexamethasone upon the synthesis of prostaglandins (PG) in the brain of the rat. Rats were treated with dexamethasone (20 mg/kg b.w.) and sacrificed 0–76 hr after administration of the drug. The rate of synthesis and release of PGE₂ was followed by 1 hr of incubation of slices of cortex taken from these rats, in Krebs-Ringer solution. A significant inhibition occurred at 8 hr and maximal inhibition (45%) was attained at 16 hr after injection. A gradual increase in the rate of synthesis up to control values occurred between 24 and 76 hr. A dose-response study, at the range of 2–40 mg/kg, showed that a significant decrease was noted at 6 mg/kg and it was maximal (45% inhibition) at 20 and 40 mg/kg. Administration of dexamethasone-sodium-phosphate, as well as other synthetic glucocorticoids and various steroidal hormones (20 μM), failed to inhibit the biosynthesis of prostaglandins under the same experimental conditions. The effect of dexamethasone and dexamethasone phosphate on synthesis of PGE₂ was also studied under in vitro conditions at 5 and 20μM. When slices of cortex from intact rats were incubated for 1 or 2hr in the presence of either dexamethasone or dexamethasone phosphate only dexamethasone was effective in inhibiting the synthesis of PGE₂.

The present results demonstrate that the inhibition of the synthesis of prostaglandins in brain by dexamethasone is both time- and dose-dependent. The lack of effect of closely related glucocorticoids demonstrate that the effect is highly specific to dexamethasone.     

Effects of acute intermittent exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on neuroendocrine function in the diestrous rat

Summary Diestrous female rats were exposed to the smoke from one to four cigarettes. Exposure to unfiltered cigarette smoke produced dose- and time-dependent reductions of catecholamine levels and dose- and time-dependent increase in catecholamine utilization in the various hypothalamic and preoptic dopamine and noradrenaline nerve terminal systems. These effects were counteracted by pretreatment with the ganglion blocking agent mecamylamine (1 mg/kg). Exposure to cigarette smoke was also found to produce a dose- and time-dependent inhibition of serum prolactin, LH and FSH levels which was counteracted by pretreatment with mecamylamine. Exposure to the smoke from one cigarette (but not from four cigarettes) increased serum TSH levels. In combination with tyrosine hydroxylase inhibition the exposure to cigarette smoke produced a dose- and time-dependent inhibition of plasma ACTH levels, an action which was counteracted by pretreatment with mecamylamine. The results demonstrated a sex difference (cf. Andersson et al. 1985c), in the nicotine-induced changes of TSH and ACTH secretion despite a general increase in hypothalamic and preoptic dopamine and noradrenaline utilization in both the male and the diestrous female rat. The differences in the neuroendocrine actions of acute intermittent exposure to cigarette smoke in the diestrous rat and the normal male rat are discussed. Send offprint requests to K. Andersson     

Effects of acute continuous exposure of the rat to cigarette smoke on amine levels and utilization in discrete hypothalamic catecholamine nerve terminal systems and on neuroendocrine function

Summary The effects of acute continuous exposure to the smoke from 1–4 cigarettes have been studied in the male rat in terms of hypothalamic catecholamine levels and utilization as well as the secretion of anterior pituitary hormones. Catecholamine levels in discrete hypothalamic catecholamine nerve terminal systems were studied by quantitative histofluorimetry. Catecholamine utilization was studied by means of the tyrosine hydroxylase inhibition method using -methyl-(±)-p-tyrosine methyl ester. The serum hormone levels of adenohypophyseal hormones and of corticosterone were measured by the use of radioimmunoassay procedures. The results show that acute continuous exposure to unfiltered but not to filtered (Cambridge glass fibre filters) cigarette smoke leads to small but dose-dependent reductions of amine levels in most of the hypothalamic noradrenaline and dopamine nerve terminal system. These effects were associated with an enhancement of regional hypothalamic noradrenaline utilization but not of dopamine utilization in the median eminence. Furthermore, a reduction of TSH and prolactin serum levels was noted as well as increases in ACTH secretion. These results are partly different from those previously obtained with rats acutely exposed to intermittent unfiltered cigarrete smoke. This difference is suggested to be due to a temporary blockade of catecholamine release following acute continuous exposure to cigarette smoke.This work has been supported by a grant (1223) from the Council for Tobacco Research, New York, USA and by a grant from the Svenska Tobaks monopolet Send offprint requests to K. Andersson at the above address     

恶性肿瘤合并抗利尿激素分泌异常综合征13例临床分析

目的 分析合并抗利尿激素分泌异常综合征(SIADH)的恶性肿瘤患者的临床及实验室检查特点.方法 回顾性分析13例对ADH患者的原发肿瘤、临床特点、诊断及治疗情况.13例SIADH患者,基础疾病均为恶性肿瘤.患者无特殊临床症状,低钠血症的相关临床症状主要为倦怠、乏力、纳差、恶心、淡漠和头昏.结果 经限制液体摄入和补充氯化钠后,12例患者血钠水平恢复正常,5例小细胞肺癌化疗有效.结论 并发SIADH的肿瘤患者预后较差,应尽早诊断,必须限制液体入量和有效控制肿瘤.     

The effects of desipramine on thyroid hormone concentrations in rat brain

The effects of the antidepressant desipramine on the tissue concentrations of thyroxine and triiodothyronine in 9 different regions of the brain and also in the pituitary and liver were investigated in male rats. The investigations were carried out at three different times of the light/dark cycle: 5 a.m., 1 p.m. and 11 p.m. After fourteen days' treatment with 20 mg/ kg/day desipramine by gavage the concentrations of triiodothyronine in the frontal and parieto-occipital cortex were significantly higher than in the saline-treated controls, those in the hippocampus lower and those in the 6 remaining brain regions the same. In 8 areas of the brain the concentrations of thyroxine were lower in the desipramine-treated rats and the tissue ratios of triiodothyronine to thyroxine were enhanced in 6 regions. These effects are most likely the result of the action of desipramine on the activity of the isoenzyme 511 deiodinase. This enzyme catalyzes the deiodination of thyroxine to triiodothyronine in rat brain and its activity has recently been reported to be enhanced by desipramine. The observed effects were dose-dependent and also strongly dependent upon the time within the 24 h light/dark cycle at which the hormone concentrations were measured. No effects of desipramine were seen in the pituitary or liver after 14 days' treatment, or in various areas of the central nervous system 24 h after administration. In view of the psychotropic properties of thyroid hormones, it seems possible that the observed increases in triiodothyronine concentrations, particularly in cortical areas, are involved in the mechanisms of action of desipramine.     

Chronic lead treatment affects dopaminergic control of prolactin secretion in rat pituitary

The effect of lead exposure on dopaminergic mechanisms regulating prolactin (PRL) secretion was studied in rats by measuring dopamine (DA) and dihydroxyphenylacetic acid hypothalamic concentrations and DA receptor density in the hypothalamus and pituitary of lead-exposed animals. [³H]sulpiride was used as dopamine receptor ligand. A decrease of dihydroxyphenylacetic acid (DOPAC) hypothalamic concentrations and a decrease of DA receptor density in the pituitary are shown. The decreased [³H]Sulpiride binding in the pituitary is consistent with the elevated serum PRL concentrations previously described in lead-exposed rats.     

Interactions of nicotine and pentobarbitone in the regulation of telencephalic and hypothalamic catecholamine levels and turnover and of adenohypophyseal hormone secretion in the normal male rat

Summary The effects of single intraperitoneal injections of nicotine (1 mg/kg) and the sedative-hypnotic drug pentobarbitone (30 mg/kg) alone or in combination have been studied on catecholamine (CA) nerve terminal system of the hypothalamus and the forebrain and on the adenohypophyseal hormone secretion of the normal male rat.Nicotine produced discrete reductions of dopamine (DA) levels and increases of DA turnover in striatal and limbic areas of the forebrain and increases of amine turnover in different hypothalamic noradrenaline (NA) nerve terminal systems. These effects were all antagonized by simultaneous treatment with pentobarbitone. Pentobarbitone alone, however, did not modulate CA levels or turnover in the various parts of the hypothalamus and forebrain analyzed. On the other hand, pentobarbitone increased GH and prolactin secretion and in association with tyrosine hydroxylase inhibition markedly reduced corticosterone secretion. These effects were partly counteracted by nicotine in the case of GH and prolactin secretion. Furthermore, a positive interaction appears to exist between nicotine and pentobarbitone in their actions on LH secretion.The results suggest that pentobarbitone can antagonize the actions of nicotine on CA levels and turnover in various CA nerve terminal systems of the brain leading to possible reductions in nicotine induced arousal and positive reinforcement. The neuroendocrine actions of pentobarbitone do not seem to be greatly modulated through nicotinic cholinergic receptors.     

托伐普坦治疗小细胞肺癌伴抗利尿激素异常分泌综合征所致的低钠血症

目的：观察托伐普坦治疗小细胞肺癌伴低钠血症的效果。方法：确诊小细胞肺癌伴抗利尿激素异常分泌综合征患者7例,均予以托伐普坦,每日口服1次：7.5 mg,前3天;15 mg,后4天,于第4天、第8天晨查血钠和体质量,并进行ECOG评分。结果：与治疗前比较,所有患者血钠均恢复正常,ECOG评分亦有显著改善,且体质量呈下降趋势。结论：托伐普坦应成为小细胞肺癌伴抗利尿激素异常分泌综合征所致的低钠血症患者的推荐用药。     

Chronic toxicity and reversibility of antifertility effect of immunization against gonadotropin-releasing hormone in male rats and rabbits.

The chronic systemic toxicity of immunization with gonadotropin-releasing hormone, conjugated to tetanus toxoid (GnRH-TT), was investigated in male rats and rabbits in order to start Phase I clinical trials. Groups of rats and rabbits were immunized with GnRH-TT dissolved in aqueous adjuvant. The antigen was administered at weeks 0, 4, and 8, followed by boosters to maintain high antibody titers. At termination (8-9 months after first immunization), twenty rats and ten rabbits exhibiting the highest mean anti-GnRH titers and all the controls were selected for complete toxicological evaluation. In the rat study, a castrated control group was included for comparison with the immunized group. The hematological and serum chemistry parameters of immunized rats and rabbits were not affected in a significant manner. Most of the changes in serum chemistry of immunized rats were also found in castrated rats, indicating that the changes are most likely due to the withdrawal of androgenic support. The weights of the testes, epididymides, and sex accessory glands were lower in all immunized animals. There was significant atrophy of the germinal epithelium, which, however, sustained a population of Sertoli cells, spermatogonia, and pachytene spermatocytes. Other morphological changes in the prostate, seminal vesicles, pituitary, and mammary gland reflected the effect of androgen withdrawal. The decrease in the weight of liver, kidney, and heart seen in the immunized rats was also present in castrated rats and was not associated with any histopathological changes. The reversibility of immunization-induced infertility was investigated by mating the rats with normal females. Four months after the start of immunization, 9 out of 10 immunized rats were infertile whereas by nine months, all rats had regained fertility. Thus, it is concluded that immunization with GnRH-TT had no systemic toxicological effects in the adult male rats and rabbits for the period studied. The results also indicated that the GnRH-TT immunization had an antifertility effect in male rats. Fertility was restored following cessation of immunization and decline in anti-GnRH antibody titers.