噻庚啶对失血性休克兔血浆SOD活性和MDA含量的影响

３０只免随机分为噻庚啶治疗组和空白对照组各１５只。颈动脉放血至血压５．３ｋＰａ，维持９０ｍｉｎ，复制失血性休克模型。于输血输液（对照组）和给药（噻庚啶１０ｍｇ／ｋｇ）后３０ｍｉｎ分别由颈动脉采取血样，测定血ＳＯＤ活性和血清ＭＤＡ含量。结果显示，噻庚啶明显地升高ＳＯＤ活性（Ｐ＜０．０１），降低ＭＤＡ含量（Ｐ＜０．０１）。氧自由基在休克的发生发展过程中起着重要作用，巴庚啶能够清除氧自由基，进而减轻细胞损伤和多器官功能衰竭，是其抗休克作用机理之一。     

Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin,ACTH, and cortisol secretion

Summary In a previous study we observed that calcitonin increases -endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma -endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. -endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of -endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.     

赛庚啶对小鼠脑缺血再灌后学习记忆行为的影响

目的 :观察赛庚啶对小鼠脑缺血后学习记忆行为的影响。方法 :用昆明系小鼠夹闭双侧颈总动脉 ,脑缺血 15min后复灌模型 ,按组分别静脉注射赛庚啶 2mg·kg-1·d-1,尼莫地平 2mg·kg-1·d-1及对照组生理盐水 10ml·kg-1.d-1。人工常规饲养一周后 ,检测开场行为、回避反应和水迷宫试验以观察小鼠学习记忆行为的改变。结果 :赛庚啶组首次检测结果与 2 4h后再次检测结果比较均有显著差异 ,而对照组则均无显著改变。结论 :结果表明该脑缺血复灌损伤可导致记忆障碍 ,赛庚啶对小鼠脑缺血后的记忆保持有较好的改善作用     

赛庚啶对大鼠垂体-性腺轴功能的影响

目的　研究赛庚啶对大鼠垂体 性腺轴内分泌功能的影响。方法　用放射免疫分析法 (RIA)和电镜 ,观察赛庚啶对大鼠垂体 性腺轴内分泌功能及垂体促性腺细胞、卵巢、睾丸细胞超微结构的影响。结果　赛庚啶 2 .3mg·kg-1·d-1,ig ,连续用药14d ,可明显降低雌性大鼠血清卵泡刺激素 (FSH)、孕酮 (P)的含量 (P <0 .0 1) ,而升高黄体生成素 (LH)的水平 (P <0 .0 5 )。 4 .6mg·kg-1·d-1赛庚啶不但可引起雌性大鼠血清FSH、雌二醇 (E2 )、P的水平显著降低 ,升高LH的含量 (P <0 .0 5及 <0 .0 1) ,而且使雄性大鼠血清LH、T的含量明显升高 (P <0 .0 5 )。组织形态电镜观察 ,该药亦可引起大鼠卵巢细胞超微结构的退行性改变 ,睾丸支持细胞呈分泌状态 ,而垂体促性腺分泌细胞则无明显变化。结论　赛庚啶可抑制雌性大鼠FSH、E2 、P的分泌 ,促进雌、雄大鼠LH及雄性大鼠T的分泌 ,其机制可能与赛庚啶直接影响靶器官的分泌细胞有关。     

Hospital Management of Acute Iron Ingestion

Abstract

This overview summarizes the major and minor side effects and drug interactions of fluoxetine. The adverse reactions include the “serotonin syndrome”, cardiovascular complications, extrapyramidal side effects such as akathisia, dyskinesias, and parkinsonian-like syndromes and an apparently increased risk of suicidality. Fluoxetine-induced mania and hypomania, seizures and sexual disorders are evaluated along with minor symptoms of allergic reactions, stuttering, hematological changes, psoriasis, and inappropriate secretion of the antidiuretic hormone. The major fluoxetine-drug interactions involve the amino acids L-dopa and L-tryptophan, anorexiants, anticonvulsants, antidepressants, anxiolytics, calcium channel blockers, cyproheptadine, lithium salts, and drugs of abuse. The underlying mechanism and the paradoxical effects of fluoxetine are addressed.     

Cyproheptadine is an effective appetite stimulant in cystic fibrosis

Chronic pulmonary infection and intestinal malabsorption often lead to malnutrition in children and adults with cystic fibrosis (CF). Appetite stimulants, along with provision of adequate calories, may aid in overcoming nutritional deficits, allowing a better prognosis. We undertook a trial of cyproheptadine hydrochloride (CH) to determine its effectiveness as an appetite stimulant in 18 adults and children with CF. This was a 12-week, randomized, double-blind, controlled trial of CH vs. placebo. Eighteen subjects with documented CF (sweat or genetics positive), minimum age of 5 years, and ideal body weight for height <100% were entered, and 16 completed the study. Subjects were seen at baseline and every 4 weeks. Measures included baseline demographics, Shwachman score, anthropometrics (weight, height, body mass index, skin folds, and body composition by bioelectric impedance analysis), spirometry, caloric intake, days of oral (PO) and intravenous (IV) antibiotics, and a symptom and satisfaction survey. Subjects in the CH group showed significant increases in weight (mean 3.45 kg vs. 1.1 kg in the placebo group), height, BMI percentiles, ideal body weight/height, weight for age z-scores, and fat and fat-free mass. There were no changes or differences in PO or IV antibiotic use or spirometric changes. No significant side effects except transient mild sedation occurred in the CH group. Patient acceptance was good. In conclusion, CH appears to be an effective appetite stimulant with minimal side effects in children and adults with CF.     

多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用

AIM: To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT) and arachidonic acid (AA) in human platelet aggregation. METHODS: Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca^2 was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method. RESULTS: Subthreshold concentration of 5-HT (2μmol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC50=5.2 nmol/L; cyproheptadine IC50=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC5o=30 nmol/L), showing that the effect is receptor-mediated.To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC50=3 μmol/L and verapamil; IC50=5 μmol/L), phospholipase C (PLC) inhibitor (U73122;IC50=4 μmol/L), cyclooxygenase inhibitor, (indomethacin; IC50=0.2 μmol/L) and mitogen-activated protein (MAP) kinase inhibitor (PD98059; IC5o=3 ktmol/L). The effect was also inhibited by a specific tyrosine light chain kinase(TLCK) inhibitor, herbimycin A with IC50 value of 5 μmol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil. CONCLUSION: The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca^2 , COX, and MAP kinase pathways.     

赛庚啶对2型糖尿病糖代谢的影响

目的 探讨赛庚啶对２型糖尿病糖代谢的影响及其机理。方法 随机选择２型糖尿病４９例，在标准饮食的基础上分别服用赛庚啶，赛庚啶加美吡达及单独服美吡达，自身比较不同处治方案前后血糖，血胰岛素，Ｃ－肽，皮质醇及生长激素的差异。结果 ①服用赛庚啶后，餐后２ｈ血糖比服药前平均下降２．０３ｍｍｏｌ／Ｌ；②服用美吡达后，２ｈＢＧ比服药前下降３．３ｍｍｏｌ／Ｌ；③美吡达合用庚啶后２ｈＢＧ比服药前下降６．１７ｍｍｏｌ     

微电泳导入赛庚啶对丘脑束旁核痛单位自发放电的影响

用多管微电极记录大鼠丘脑束旁核(Pf)痛单位放电。观察微电泳导入5-羟色胺(5-HT)阻断剂赛庚啶(Cyproheptadine,Cyp)对Pf痛单位自发放电的影响。结果表明,Cyp增加丘脑束旁核痛兴奋(PfPE)单位的自发放电频率,减少痛抑制(PfPI)单位的自发放电频率。提示,Cyp可能通过阻断内源性5-HT调制Pf痛单位的活动。     

A comparative study of cyproheptadine and DL carnitine on psychomotor performance and memory in healthy volunteers

This study was performed in order to investigate the extent and severity of cyproheptadine effects on psychomotor performance, mood and memory functions and to compare them to the effects of DL carnitine, another appetite stimulant. Twelve healthy volunteers received 2 doses (at 800 am and 1200 am) of 6 mg cyproheptadine, 1600 mg DL carnitine and placebo on separate days at a weekly intervals. The study followed a double-blind, latin-square design. Assessment of dependent variables was performed 1 h after the first and 1 h and 5 h after the second administration of the drug. On each of these occasions, the following measurements were performed: choice reaction time (CRT), critical flicker fusion (CFF), digit symbol substitution test (DSST), short-term memory (paired words association test), long-term memory (picture test) and 100 mm visual analogue scales of subjective ratings (VAS). Cyproheptadine significantly impaired objective measures (CFF) and subjective ratings both at 1 h and 5 h after the second dosage. Compared with cyproheptadine, DL carnitine induced a slight improvement in psychomotor performance as assessed by CRT. None of the drugs had any effect on memory and on appetite at the doses studied. In conclusion, cyproheptadine at usual doses had a sedative effect, the intensity and duration of which implied a certain risk in performing daytime functions eg when driving, or manipulating machines. DL carnitine had no effect on vigilance.