赛庚啶对大鼠垂体-肾上腺皮质轴作用及机制的研究

目的　研究赛庚啶 (cyproheptadineCyp)对大鼠垂体 肾上腺皮质轴内分泌功能及机制的影响。方法　用放射免疫分析法 (RIA)观察Cyp对大鼠血清ACTH、可的松水平的影响。用电镜及荧光定量PCR技术 ,观察Cyp对ACTH细胞、肾上腺皮质束状带细胞超微结构及钙调素 (calmodulinCaM)mRNA在垂体、肾上腺皮质基因表达的影响。结果　Cyp 2 3、4 6mg·kg- 1 ·d- 1 ,ig,连续用药 1 4d ,可使大鼠血清ACTH和可的松含量降低 (P <0 0 5 ,P <0 0 1 )。组织形态电镜观察 ,该药亦可引起大鼠垂体ACTH细胞、肾上腺皮质束状带细胞超微结构的退行性改变。同时发现CaMmRNA在垂体、肾上腺皮质的基因表达较对照组减少 (P <0 0 5 ,P<0 0 1 )。结论　Cyp对大鼠垂体 肾上腺皮质轴分泌功能有抑制作用 ,其机制可能与抑制CaMmRNA在垂体、肾上腺皮质的基因表达有关     

海洛因依赖者下丘脑-垂体-肾上腺轴功能改变

<正> 国外研究报道海洛因依赖者下丘脑-垂体-肾上腺轴功能受损,但国内尚未见有关报道,为了解中国海洛因依赖者下丘脑-垂体-肾上腺轴功能情况,本研究中心检测了54例海洛因依赖者和30例正常人血浆ACTH和皮质醇水平。结果显示海洛因依赖者上午8时的血浆ACTH和皮质醇均明显降低。而零点血皮质醇明显高于对照组(P<0.01)。这结果提示长期滥用阿片类药物可改变下丘脑和肾上腺素机能。综合国内外研究结果提示,测定ACTH和皮质醇可作为评     

小儿脑性瘫痪的分类

脑性瘫痪(Cerebral Palsy)是从妊娠期至新生儿期由多种原因引起的大脑非进行性损伤性疾病,临床症状表现为持续性的运动障碍及姿势异常,可伴多种并发症。它是造成儿童肢体伤残的主要疾病之一,国外发病率为1～2‰,我国大约1.8～6‰。 1 小儿脑性瘫痪分类的历史 1893年Freud将临床表现相似,而病因各异的痉挛性瘫痪所有类型统为一类,命名为小儿脑性瘫痪。同时他最先提出本病分类法,将本病分为六类,先大性脑性瘫痪伴全身运动障碍;瘫痪性运动障碍;痉挛性截瘫;两侧性偏瘫;舞蹈病;双侧手足徐动症。     

小儿脑性瘫痪康复治疗研究进展

小儿脑性瘫痪(脑瘫),即患儿出生前后1个月所致的非进行性脑损伤,直接导致患儿运动障碍及姿势异常。有研究资料显示国外脑瘫患病率为2‰～3‰[1],而我国1～7岁小儿脑瘫患病率为1.2‰～2.7‰[2]。近年来,脑瘫已成为儿童致残     

50例脑性瘫痪患儿牙颌畸形的临床分析

脑性瘫痪(Cerebral palsy)国内的发病率为1.8‰—4‰,随着社会文明程度的提高和生活水平的改善,已经引起社会和患者家属的重视,并在医学界开展了深入的研究。脑性瘫痪的临床特点表现为非进行性中枢性运动障碍,但同时电伴有继发性的器官发育异常,和相应的机能障碍。在国内外有较多报道,本文对50例脑性瘫痪患儿进行了牙颌畸形的调查,结果如下。1 对象和万法①对象:为1989年9月—1994年3月间在佳术期医学院省脑瘫疗育中心收治住院的脑瘫患儿50例,其中男38例,女12例。年龄为2.5—8.5岁,平均4.1岁,均系汉族人。②方法:采用一人一卡制的常规口腔检查方法,内容包括牙、颌、颅面部三大类。诊断及临床分型以全     

吗啡对神经内分泌系统的影响及机制

本文初步总结了吗啡在依赖过程中对下丘脑-垂体-肾上腺皮质轴(HPAA)的影响及机制,观察血中β-内啡肽(β-EP)、促肾上腺皮质激素(ACTH)、皮质醇、性激素等浓度的改变及机制,并简单比较海洛因与吗啡对神经内分泌系统各激素水平浓度影响的不同.     

应用Bobath法治疗脑瘫患儿189例的体会

脑性瘫痪是从受孕至新生儿期各种原因所至的非进行性脑损伤而引起的综合征，主要临床表现为运动障碍和姿势异常，发病率高达1.8‰~4‰。脑性瘫痪常常合并智力低下、癫痫、行为异常、语言障碍等，是目前致小儿残疾的主要疾病。Bobath法是目前世界上治疗脑性瘫痪的主要方法之一，是一种被国际公认的有效方法。Bobath法当前在世界上被广泛应用，我院从1986年引进此法，治疗了大量脑性瘫痪患儿，取得了良好的疗效。笔者十余年来应用此法治疗了脑性瘫痪患儿189例，本文分析疗效，总结心得体会。 1 资料与方法 1.1 临床资料 1986-10~2001年底于…     

P物质对哮喘大鼠神经内分泌功能的调节

目的探讨哮喘大鼠脑内P物质在哮喘发作中的作用。方法以大鼠腹腔注射含百日咳和氢氧化铝的卵蛋白溶液制备哮喘动物模型,免疫组织化学方法(SABC)检测哮喘大鼠脑内c-fos蛋白,放射免疫法检测下丘脑室旁核(para-ventricular nucleus,PVN)内P物质(substance P,SP)的含量及正中隆起(ME)中促肾上腺皮质激素释放激素(cortico-tropin-releasing hormone,CRH)和外周血中促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticoster-one,CORT)含量,PVN内分别微量注射外源性SP、SP受体拮抗剂S0145,观察其对哮喘大鼠肺功能与下丘脑-垂体-肾上腺皮质功能轴(hypothalamus-pituitary-adrenal axis,HPA轴)活动的影响。结果哮喘大鼠发作时PVN内SP含量升高;正中隆起CRH与外周血中ACTH、CORT含量均降低(P<0.05),呼/吸时程比和气道阻力增加,膈肌放电积分、肺顺应性减小(P<0.01)。PVN内微量注射SP后哮喘大鼠的肺通气功能进一步下降,CORT、ACTH、CRH含量进一步降低(P<0.01)。SP受体阻断剂S0145则可逆转哮喘发生时大鼠肺功能与HPA轴的改变。结论哮喘大鼠下丘脑室旁核内SP可影响HPA轴的功能,参与哮喘发作。     

参姜锁阳益气片对寒凝气滞血瘀证大鼠下丘脑-垂体-肾上腺皮质轴及中枢神经递质的影响

目的 探讨参姜锁阳益气片对寒凝气滞血瘀证大鼠下丘脑-垂体-肾上腺皮质轴及中枢神经递质的影响。方法 清洁级SD大鼠36只,随机选取6只为A组,其余30大鼠采用肾上腺素加冰水浴复合低温冷冻法建立大鼠寒凝气滞血瘀证模型,造模成功后随机分为B、C、D、E、F组,每组6只。各组于末次造模后1 h灌胃给药,C、D、E组给予参姜锁阳益气片70、140、280 mg/kg,F组给予大株红景天胶囊280 mg/kg,A、B组给予等体积生理盐水,每日1次,连续2周。采用酶联免疫吸附试验(ELISA)检测血中垂体前叶促肾上腺皮质激素(ACTH)和肾上腺皮质酮(CORT)水平,脑组织多巴胺(DA)、5-羟色胺(5-HT)和去甲肾上腺素(NE)含量。结果 与B组比较,C、D、E、F组血清中ACTH、CORT水平降低,除C、D组脑组织中DA外,其余各组脑组织匀浆中DA、5-HT和NE含量均有不同程度的降低(P<0.05,P<0.01);与F组比较,C组血中CORT水平和脑组织匀浆中DA、5-HT和NE含量显著升高,E组血中ACTH、CORT水平和脑组织匀浆中DA含量降低(P<0.05,P<0.01)。结论 参姜锁阳益气片能够通过下丘脑-垂体-肾上腺皮质轴调节有关激素的水平,同时能调节相关中枢神经递质的含量,从而调控体温,起到对机体的保护作用。     

ACTH治疗原发性肾病综合征复发患儿的疗效及安全性观察

目的：探讨糖皮质激素（ GC）、促肾上腺皮质激素（ ACTH）在肾病综合征复发患儿中的疗效及安全性。方法选取激素敏感型原发性肾病综合征患儿为研究对象,其中95例患儿在停用激素后复发或治疗期间复发,将重新采用糖皮质激素治疗或上调激素剂量治疗的患儿纳入GC组,采用ACTH治疗的患儿纳入ACTH组,观察治疗前与治疗期间两组患儿激素用量、临床疗效、不良反应及肾上腺皮质功能变化。结果 ACTH 组35例（83.3%）治疗期间未再复发,7例（16.7%）患者因感染导致频繁复发,治疗无效。 GC组41例（77.4%）治疗有效,12例（22.6%）单纯激素治疗效果不明显。 ACTH组与GC组总有效率无显著差异（P〉0.05）。 ACTH组患儿GC用量显著高于GC组（P〈0.05）、身高增加显著高于高于GC组,体重增加显著高于低于GC组、肾上腺皮质功能降低显著低于GC组（P均〈0.05）。结论 ACTH 方案治疗原发性肾病综合征复发患儿效果肯定,可降低糖皮质激素使用剂量、改善患儿生长发育的抑制、减轻避免肾上腺皮质功能降低。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.