慢性失眠病人脑内神经递质活动的超慢涨落图表现

目的:探讨慢性失眠病人脑内神经递质活动变化.方法:用WF92型脑电超慢涨落分析仪,通过检测慢性失眠病人和正常人的脑电超慢涨落图(EFG),分析其谱线变化来反映脑内神经递质活动变化.结果:慢性失眠病人51例与51例健康人配对对照比较,EFG 神经递质谱系S1和S2显著降低(配对t检验,P<0.01),S3、S4、S5、S7和S11两组间比较无明显差异,提示慢性失眠病人脑内神经递质谱系S1 γ-氨基丁酸(GABA)和S2谷氨酸(Glu)活动存在异常,S3乙酰胆碱受体(Ach-R)、S4 5-羟色胺(5-HT)、S5乙酰胆碱(Ach)、S7去甲肾上腺素(NE)和S11多巴胺(DA)活动无明显变化.结论:脑内神经递质GABA和Glu活动异常可能参与了慢性失眠的发病.     

几种神经递质对大鼠丘脑底核神经元自发放电活动的影响

采用微电泳法观察了谷氨酸（Glu）、乙酰胆碱（Ach）、多巴胺（DA）和γ－氨基丁酸（GABA）等药物对大鼠STN神经元自发放电活动的影响。结果表明：Ach、Glu和DA分别使67．05％（59／88），92．94％（79／85），90．02％（80．06）神经元自发放电频率加快，它们的作用依赖于电流强度。GABA抑制所有神经元的自发放电活动，其作用也依赖于电流强度。在微电泳Ach或Glu过程中，给予GABA可拮抗其兴奋作用。双钴碱（Bic）可使78．79％）（52／66）的神经元自发放电频率加快，阿托品（ATR）可使60％（15／25）神经元自发放电减少，给药前后放电频率差异显著（P＜0．05）。而MK－801对STN自发放电影响较小，但能拮抗Glu的兴奋作用。结果表明：GABA、Ach、Glu和DA等递质活动在同一STN神经元有重要会聚作用，GABA和Ach分别对STN神经元有紧张性抑制性及兴奋作用。     

褶纹冠蚌的脑、足神经节内Glu、GABA、5-HT、ACh和DA能神经元的分布

目的:观察谷氨酸(glutamate,Glu)、γ-氨基丁酸(γ-aminobutyric acid,GABA)、5-羟色胺(5-hydroxytryptamine,5-HT)、乙酰胆碱(acetylcholine,ACh)和多巴胺(dopamine,DA)神经元在褶纹冠蚌中枢神经系统内的分布。方法:免疫组织化学染色技术和免疫印迹技术。结果:脑神经节外侧胞体层存在大量的GABA能神经元,偶见胞体较大的Glu、5-HT、ACh和DA能神经元,其中央纤维网可见丰富的GABA能神经末稍及少量的Glu、5-HT、ACh和DA能神经末梢。足神经节外侧胞体层亦含有大量的GABA能神经元,可见散在的Glu、5-HT、ACh和DA能神经元,其中央纤维网可见丰富的GABA能神经末稍及零星的Glu、5-HT、ACh和DA能神经末梢。结论:褶纹冠蚌脑和足神经节均含有GABA、Glu、5-HT、ACh和DA能神经元,但这五类神经元的数量和密度有所不同。     

基于脑内神经递质对的拮抗关系建立新型抑郁症大鼠模型的实验研究

目的:利用脑内神经递质对的拮抗关系建立新型抑郁症大鼠模型。方法:通过海马微量注射低、中、高剂量(1、2和4 g/L)的多巴胺D1受体拮抗剂SCH23390造模后,利用糖水消耗实验、旷场实验及新环境进食抑制实验等评价动物抑郁行为表现,以筛选出最佳造模药物剂量。应用最佳造模剂量造模后,连续观察,2周后对该模型进行评价,通过行为学测试评价该模型症状的稳定性,采用ELISA法测定脑脊液中IL-1β和TNF-α的含量评价该模型的安全性,采用高效液相色谱-质谱技术(HPLC-MS)定量检测大脑皮层和海马中5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)、乙酰胆碱(ACh)、谷氨酸(Glu)和γ-氨基丁酸(GABA)等神经递质的水平,以此评价该模型脑内神经递质失衡的病理特征。结果:造模结束后,各剂量造模组大鼠体重、糖水偏爱率、水平运动得分和垂直运动得分均明显降低,新环境进食抑制时间增长,表现为典型的抑郁样行为,以中剂量造模组大鼠的抑郁行为表现最为显著;造模后2周,与正常对照组相比,中剂量造模组大鼠的体重、糖水偏爱率、水平运动得分和垂直运动得分均明显降低(P0.01),新环境进食抑制时间增长(P0.05)。正常对照组、空白对照组和中剂量造模组大鼠脑脊液中IL-1β和TNF-α的含量均无显著变化,说明该模型未造成明显炎性损伤,造模方法安全。与空白对照组相比,中剂量造模组大鼠左侧海马5-HT、NE和Glu含量均显著升高(P0.01),DA和ACh含量均呈降低趋势;右侧海马5-HT、NE和Glu含量均显著升高(P0.05),DA和ACh含量均呈降低趋势;大脑皮层Glu含量显著升高(P0.05),5-HT和NE含量均呈升高趋势,DA和ACh含量均呈降低趋势,说明该模型基本符合抑郁症脑内神经递质失衡的病理特征。结论:此方法可成功复制抑郁症大鼠模型,该模型具有症状典型而持久、成模快速、操作简便安全等特点,较合适的造模药物剂量为2 g/L。     

芪参复康胶囊治疗抑郁症的临床疗效观察

目的采用自身前后对照的方法观察芪参复康胶囊治疗抑郁症疗效。方法对30例抑郁症患者在治疗前及治疗6周后行汉密尔顿抑郁量表(HAMD)、抑郁自评量表(SDS)和脑电超慢涨落图检查,分析其治疗前后症状和脑内神经递质的变化。结果①抑郁症患者经芪参复康胶囊治疗6周后,HAMD总分和SDS总分均下降(t=15.95,11.81;P均<0.05),差异具体统计学意义;②抑郁症患者在治疗6周后脑内神经递质测量值较治疗前均有所变化,其中,5-羟色胺(5-HT)活动性降低,去甲肾上腺素(NE)、多巴胺(DA)活性增强(t=9.61,12.60,9.44;P<0.05),差异均具有统计学意义。结论纯中药制剂芪参复康胶囊治疗抑郁症疗效肯定。     

可达灵对小鼠脑内单胺类和氨基酸类神经递质影响的研究

目的 探讨可达灵对正常小鼠脑内单胺类和脑缺血小鼠脑内氨基酸类神经递质的影响。方法 在小鼠灌胃不同剂量的可达灵后，用HPLE测定脑内单胺类神经递质。同时采用结扎小鼠双侧颈动脉造成脑缺血，观察可达灵对脑内谷氨酸(Glu)/γ一氨基丁酸(GABA)的影响。结果 可达灵可以升高脑内5-羟色胺(5-HT)和多巴胺(DA)的含量，并且能够抑制深度脑缺血时脑内Glu／GABA比例的降低。结论 可达灵对小鼠脑缺血引起的损伤具有一定保护作用，而且有一定镇痛作用。     

氯化镧对大鼠生长素分泌调节影响的体外研究

目的：研究氯化湖（LaCl3）对大鼠生长素分泌调节轴的影响。方法：采用荧光法检测离体脑片培育液中单胺类神经递质含量;用放射免疫法测垂体脑片育液中生长素（GH）含量。结果：①0．01mmol／LLaCl3垂体组育液中GH含量明显高于对照组（P＜0．05）;而1mmol／LLaCl3垂体组有液中GH含量明显低于对照组（P＜0．05）。②0.01mmol／LLaCl3下丘脑＋垂体组,其有液中GH含量则明显高于对照组（P＜0．01）和同剂量的单纯垂体组（P＜0．01）;但1mmol／L下丘脑＋垂体组育液中GH含量与对照组比较无显著差异（P＞0．05）。③0．01mmol／LLaCl3下丘脑组有液中NE含量明显高于对照组（P＜0．01）,5－HT明显低于对照组（P＜0.05）。④1mmol／L下丘脑组有液中NE和DA含量明显少于对照组（P＜0．01和0．05）,而5－HT含量则明显高于对照组（P＜0．001）。结论：低剂量氯化调可通过下丘脑和腺垂体双重作用促进GH分泌。     

路优泰治疗抑郁症的疗效观察

抑郁性精神障碍被视为一种致残性精神疾病，一般人群中终生患病率达10％，由于三环类等抗抑郁药物的不良反应，使得抑郁症患者治疗的依从性大大降低，从而使症状得不到有效改善，严重影响了生活质量。路优泰-圣．约翰草提取物，是一种抗抑郁药物。它含贯叶金丝桃素和金丝桃素等成分，不但能够多途径的均衡增加脑中三种单胺类神经递质（5-HT、NE、DA）的浓度，而且能调节神经免疫内分泌网络功能，因而从根本上治疗抑郁症。本研究应用路优泰治疗抑郁症，观察该药起效的时问，疗效、不良反应和耐受性。     

PCOS合并不孕症患者心理健康状况及其与单胺神经递质的关系

目的：了解PCOS和非PCOS不孕症患者的心理健康状况、血清中单胺类神经递质的浓度，并探讨心理健康状况与其血清中单胺类神经递质浓度之间的关系，为不孕症的综合性治疗提供资料。方法：从本院不孕症门诊收集PCOS及非PCOS不孕症初诊患者各30例作为实验组和对照组，所有入组对象均完成精神症状自评量表（SCL-90）的自我测评和血清NE及代谢物MHPG，DA及代谢物HVA、DOPAC，5-HT及代谢物5-HIAA浓度的测定。结果：对两组的SCL-90各因子分进行比较．结果发两组在抑郁、焦虑因子得分上有明显的差异（P≤0．05）。实验组与对照组比较，其血清中5-HT及其代谢产物5-HIAA浓度，DA代谢产物HVA均明显低（P≤0．05），其它指标两组之间无显著性差异。在总体样本中，SCL-90的恐怖因子分与MHPG血清浓度呈显著正相关（r=0.277，P=0.03），在实验组SCL-90的敌对因子分与血清DOPAC浓度呈显著负相关（r=-0．416，P〈0．02）。结论：PCOS患者较非PCOS妇女存在明显的心理障碍问题，主要表现在焦虑与抑郁情绪方面；PCOS不孕症患者的血清中5-HT及其代谢产物5-HIAA浓度，DA代谢产物HVA明显下降：心理问题可能是PCOS不孕症的重要因素之一。     

PAF拮抗剂对光化学反应后脑缺血中心区及半暗区单胺类递质的影响

目的：探讨血小板活化因子（PAF）与单胺类神经递质缺血性脑损伤中的可能机制，并观察PAF拮抗剂银杏内酯B对抗PAF所致脑缺血中心区及半暗区病理生理改变及其逆转单胺类递质代谢紊乱的作用。方法：采用光化学诱导树血栓性脑缺血模型，舌下静脉一次性注射银杏内酯B5mg·kg-1（光化学反应后6h），观察给药后缺血中心区及半暗区单胺类递质及脑水含量的变化。结果：给药组半暗区NE、DA及5－HT依次为（403．64±50.94）ng／gwt、（474．96±44．12）ng／gwt和（495．79±33．19）ng／gwt，均分别高于缺血组（254．95±42.26）ng／gwt（P＜0．01）、（403．28±34．86）ngwt（P＜0．01）和（410.58±33．24）ng／wt（P＜0．01）；而给药组半暗区脑水份含量为（81．75±0．80）％低于缺血组（83．85±0．96）％（P＜0．01）。结论：PAF与单胺类神经递质共同参与缺血性脑损伤，并且银杏内酯B能特异性拮抗PAF受体及减少单胺递质的释放而具有抗脑缺血效应。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.