金雀异黄酮对去卵巢大鼠海马突触体素表达的影响

目的：研究金雀异黄酮对去卵巢大鼠海马突触体素的影响,以探讨金雀异黄酮对女性更年期后中枢神经系统退行性变的作用机制。方法：用免疫组化结合图像分析的方法,测量分析去卵巢后不同时间点以及给予金雀异黄酮替代治疗后海马CA1～3区辐射层和齿状回分子层突触体素免疫阳性产物的平均光密度变化。结果：去卵巢后大鼠CA1～3区辐射层和DG分子层突触体素免疫阳性产物的平均光密度值逐渐降低,4周后与假手术组和苯甲酸雌二醇组相比有显著差异;金雀异黄酮组治疗后海马突触体素免疫阳性产物平均光密度恢复。结论：金雀异黄酮能恢复去卵巢大鼠海马突触密度,延缓女性更年期后中枢神经系统的退行性变。     

金雀异黄酮对去卵巢大鼠脑抗氧化作用的影响

目的研究金雀异黄酮对去卵巢大鼠大脑抗氧化作用的影响,为使用植物雌激素防治女性更年期后老年性痴呆提供依据。方法40只3月龄雌性SD大鼠,随机分为假手术组、去卵巢对照组、金雀异黄酮组和苯甲酸雌二醇组,给予相应手术和治疗。术后6周分析大鼠额叶、颞叶、海马和基底前脑的SOD和MDA值。结果假手术组颞叶和海马的SOD值低于基底前脑(P<0.05);额叶和颞叶的MDA值高于海马和基底前脑(P<0.05);去卵巢对照组基底前脑的SOD值显著低于假手术组、金雀异黄酮组和苯甲酸雌二醇组(P<0.05),MDA值显著高于假手术组、金雀异黄酮组和苯甲酸雌二醇组(P<0.05);假手术组、金雀异黄酮组及苯甲酸雌二醇组之间SOD值和MDA值差异无统计学意义(P>0.05)。结论去卵巢对照组大鼠基底前脑抗氧化能力显著降低,氧化损伤程度显著升高,金雀异黄酮替代治疗可增加去卵巢大鼠基底前脑的抗氧化能力,降低基底前脑的氧化损伤,可用于女性更年期后老年性痴呆的防治。     

脑功复得对改善脑老化作用的基础研究

实验目的:应用脑功复得口服液研究其对老龄大鼠学习记忆及大脑皮质海马突触泡膜素、Tau-蛋白的影响,探讨其延缓脑老化的功效及可能机制。实验方法:应用爬杆主动回避反应(AAR)将动物共分为学习记忆正常组和障碍组,再随机分别设置对照组(普食)和喂药组(5ml/日/鼠,2月)。再进行AAR和多功能箱被动回避反应(PAR)训练,处死动物并进行大脑皮质海马突触体计数、凋亡细胞计数、突触泡膜素免疫组化实验(ICC)及Tau蛋白ICC图像分析。实验结果:老年实验组大鼠AAR习得率较对照组明显提高、消退明显延迟、STL明显延长、大脑皮质海马突触体计数明…     

金雀异黄酮对去卵巢大鼠认知能力的影响

目的　观察金雀异黄酮对去卵巢大鼠学习记忆的影响 ,寻找替代雌激素用于防治女性更年期后神经退行性变的药物。方法　 32只 3月龄雌性SD大鼠随机分为 4组 :假手术组 (0 9%NS 5 0 μl)、去卵巢对照组 (0 9%NS 5 0 μl)、金雀异黄酮组 (Gs2 5 0 μg)、苯甲酸雌二醇组 (EB 5 0 μg)各 8只 ,皮下注射给药 ,隔日一次 ,用Morris水迷宫检测大鼠空间学习记忆能力。 结果　金雀异黄酮组前 4次和后 5次的平均逃避潜伏期 ( x±s)分别为 (2 3 34± 7 2 9)s和 (8 5 4± 1 87)s;空间探索试验中大鼠穿越平台的次数为 6 0 0± 1 1 0次 ;与OVX组相比具有显著性差异 (P <0 0 5 )。结论　金雀异黄酮可提高去卵巢大鼠的空间学习记忆能力     

P2Y_(13)受体激活促进脊髓背角小胶质细胞钙浓度升高

目的:观察ADP对培养的脊髓背角小胶质细胞内Ca2+浓度([Ca2+]i)的影响及作用机制。方法:培养纯化新生SD大鼠脊髓背角小胶质细胞,免疫组化观察P2Y13受体表达,激光共聚焦显微镜检测ADP作用下,小胶质细胞[Ca2+]i的变化。结果:大鼠脊髓背角小胶质细胞表达P2Y13受体,ADP可导致培养的脊髓背角小胶质细胞[Ca2+]i快速增高,且呈现剂量依赖性;P2Y13受体拮抗剂MRS2211(100μmol/L)能基本阻断ADP的作用,而P2Y1受体拮抗剂MRS2179(100μmol/L)、P2Y12受体拮抗剂MRS2395(100μmol/L)均不影响ADP致小胶质细胞[Ca2+]i升高的效应。结论:ADP可能通过P2Y13受体途径,导致培养的脊髓背角小胶质细胞[Ca2+]快速升高。     

慢性强迫游泳应激抑郁模型大鼠海马钙离子浓度和c-fos表达的改变

目的:观察慢性强迫游泳应激模型大鼠海马区[Ca2+]i和c-fos/Fos的变化,探讨慢性应激抑郁症与海马相关的发病机制。方法:选用雄性成年Wistar大鼠80只,将大鼠随机分为正常对照组(n=19)、急性对照组(n=12)和模型组(n=49),建立慢性强迫游泳应激抑郁模型,通过糖水偏好实验和开场实验对大鼠进行行为学测试。采用荧光分光光度法测定海马内[Ca2+]i浓度,免疫印迹技术和逆转录-聚合酶链式反应检测Fos和c-fos的表达变化。结果:与正常对照组大鼠相比较:(1)模型组大鼠相对糖水消耗量、糖水偏好百分比、直立次数和体重增长率均降低(P0.01,P0.05);(2)模型组大鼠各个时间点海马神经元[Ca2+]i增高(P0.01);(3)模型组大鼠海马Fos在应激后(0.5,1,2,4h)表达增强(P0.01),c-fosmRNA在应激后(0.5,1,2,4h)转录增强(P0.01)。与急性对照组相比较,模型组Fos蛋白表达高峰提前,表达量降低(P0.05)。结论:海马[Ca2']i及c-fos/Fos的表达变化,可能参与了抑郁症的发病过程。     

皮质酮对原代培养的海马神经元及其Ca2+/CaMKⅡ的影响

在培养液中加入10-7、10-6和10-5浓度(mol/L)的皮质酮,采用MTT染色测定、Fura-2/AM的荧光标记以及Western印迹的方法,观察了不同浓度的皮质酮作用下海马神经元形态学和细胞存活率的变化以及胞浆内游离钙离子浓度[Ca2+]i和CaMKII表达的变化规律,探讨其对原代培养的大鼠海马神经元及其Ca2+/CaMKII的影响和可能的机制.结果发现10-6、10-5浓度的皮质酮对海马神经元的形态学影响较大,与对照组比较,细胞存活率明显降低;[Ca2+]i分别为113.1022±16.9716、155.3794±20.7727;CaMKII的表达也明显减少;三者的变化均显著(P＜0.01),而10-7浓度的皮质酮对上述指标影响不大(P＞0.05).此外,相关性分析表明[Ca2+]i和CaMKII的表达呈现负相关(P＜0.05).以上结果提示,皮质酮对大鼠海马神经元的作用存在浓度依赖效应,浓度越高,对大鼠海马神经元的损伤越大,同时也验证了皮质酮是啮齿类动物的主要的应激激素.     

急性缺氧对大鼠远端肺静脉平滑肌细胞内钙浓度的影响

目的:研究急性缺氧对大鼠远端肺静脉平滑肌细胞(PVSMC)细胞内钙浓度([Ca2+]i)的影响及L型电压依赖性钙通道(VDCC)阻断剂硝苯地平的作用,为缺氧性肺动脉高压发病机制的进一步研究提供理论依据.方法:胶原酶消化法培养大鼠远端PVSMC,利用荧光显微镜和细胞内钙浓度检测系统观测急性缺氧(4％O2)、高钾(60 mmol/L KCl)溶液对PVSMC的[Ca2+]i影响及硝苯地平的干预作用.结果:对照组PVSMC的[Ca2+]i随时间变化维持基线水平;缺氧组PVSMC急性缺氧后,[Ca2+]i迅速升高并维持平台水平,△[Ca2+]i达82.83 nmol/L士23.03 nmol/L;硝苯地平干预组PVSMC予急性缺氧和5μmol/L硝苯地平干预后,[Ca2+]i升高幅度较小;高钾溶液孵育PVSMC后,[Ca2+]i迅速增高,5 μmol/L硝苯地平能完全阻断PVSMC的[Ca2+]i对高钾溶液的反应.结论:急性缺氧可使大鼠远端PVSMC的[Ca2+]i升高,其机制可能与激活PVSMC的VDCC和另外的非VDCC依赖的钙通道导致细胞外Ca2+内流有关.     

脑功复得对大鼠脑发育影响的基础研究

本课题应用脑功复得研究其对发育期大鼠学习记忆能力的影响 ,探讨其对促进脑发育的功效及可能机制。本实验中 ,1.5月龄大鼠随机分为对照组 (普食 )和喂药组 (2 ml/日 /鼠 )。喂饲 2个月后进行爬杆主动回避反应 (activeavoidance reaction,AAR)和多功能箱被动回避反应 (passive avoidance reaction,PAR)训练 ,然后处死动物进行突触体计数、突触泡膜素免疫组化染色及图像分析。结果表明 :服用脑功复得 2月后 ,喂药组较对照组 AAR习得率提高、消退延迟、步入潜伏期延长、大脑皮质海马突触体计数增高、突触泡膜素ICC增强 ,说明脑功复得能增…     

大鼠实验性甲状旁腺功能减退的研究——Ⅲ.脑突触膜流动性的改变

本实验采用荧光偏振和差示扫描量热(DSC)技术,测定了实验性甲状旁腺功能减退的大鼠模型脑突触膜流动性的改变。结果表明,2个月持续低血钙状态,使火鼠的大脑皮层、海马、纹状体和中脑的突触膜平均微粘度减小,其中大脑皮层和海马与对照组呈显著性差异(P<0.001),提示低钙鼠突触膜流动性上升。此外,低钙还使海马突触膜脂质的棚变温度Tc提前,提示膜的流动性和通透性均增加。     

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.     

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.     

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.     

'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.     

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.     

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.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.