中国劲酒对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴及免疫功能的影响

目的:研究中国劲酒对皮质酮致肾阳虚模型的大鼠下丘脑-垂体-肾上腺(Hypothalamic-pituitary adrenal,HPA)轴及免疫功能的影响。方法:取健康清洁级雄性SD大鼠45只,按随机数字表法分为空白对照组、模型组和中国劲酒组,每组15只,通过皮下注射外源性皮质酮(10 mg/kg体重)连续14天抑制HPA轴,制备肾阳虚模型。皮质酮注射前5天,以50 ml/kg体重灌胃中国劲酒(相当于中国劲酒日推荐服用剂量的30倍),连续19天。采用酶联免疫吸附试验(ELISA)方法检测血浆皮质酮(Corticosterone,CORT)含量;采用放射性免疫法测定血浆中促肾上腺皮质激素(Adrenocorticotropic hormore,ACTH)含量,采用实时定量-聚合酶链反应法(Real-time PCR)测定下丘脑促肾上腺皮质激素释放激素(Corticotropin releasing hormone,CRH)mRNA表达水平;取胸腺称重,淋巴细胞凋亡及增殖率分别采用流式细胞仪法和改良四氮唑盐(XTT)法。结果:在外源性皮质酮作用下,肾阳虚模型大鼠较空白对照组HPA轴和免疫功能受到明显抑制,中国劲酒灌胃后可显著提高大鼠下丘脑CRH mRNA水平、血浆ACTH含量,与肾阳虚模型组比较差异有统计学意义(P<0.05);血浆CORT水平有升高倾向;同时在免疫调节方面,中国劲酒可明显增加皮质酮模型大鼠胸腺重量和降低脾脏淋巴细胞凋亡率,与肾阳虚模型组比较差异有统计学意义(P<0.01);中国劲酒有促进淋巴细胞增殖的趋势。结论:中国劲酒能改善肾阳虚模型大鼠HPA轴功能;也具有改善肾阳虚模型大鼠免疫功能的作用。     

褪黑素对SD大鼠下丘脑-垂体-肾上腺皮质的影响

目的 研究褪黑素对正常和糖尿病大鼠下丘脑-垂体-肾上腺皮质功能和超微结构的影响.方法 应用放射免疫法分别观察了低、中、高剂量(0.5mg/kg、10mg/kg、50mg/kg)褪黑素及对照药物硫辛酸(100mg/kg)连续腹腔注射3周,对SD大鼠血浆促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(COR)水平的影响.并运用电镜观察用药前后大鼠垂体、肾上腺皮质超微结构的变化.结果 1.正常和糖尿病大鼠低、中、高剂量褪黑素处理组CRH水平与相应对照组相比显著降低;正常大鼠低、中、高剂量褪黑素及硫辛酸处理组和糖尿病大鼠低剂量(0.5mg/kg)褪黑素、硫辛酸处理组ACTH水平比相应对照组明显降低(P＜0.05);正常大鼠低、中、高剂量褪黑素处理组和糖尿病大鼠中高剂量褪黑素处理组皮质酮水平比相应对照组显著降低(P＜0.05).2.褪黑素对正常大鼠下丘脑-垂体-肾上腺皮质超微结构无明显影响.糖尿病大鼠垂体细胞和肾上腺皮质细胞出现功能受抑制状态,褪黑素(50mg/(kg·d))处理21d后垂体促肾上腺皮质细胞和肾上腺皮质细胞代谢较处理前明显活跃.结论 褪黑素能在不同层次直接或间接地发挥对正常和糖尿病大鼠下丘脑-垂体-肾上腺(HPA)轴的抑制作用.     

褪黑素水平对抑郁症患者下丘脑-垂体-肾上腺轴功能的影响

目的探讨抑郁症患者褪黑素(MT)水平对下丘脑-垂体-肾上腺轴(HPA)功能的影响。方法对86例抑郁症患者,检测血清MT、促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质醇(COR),并分析其相互关系。结果1以MT中位数(51.3ng/L)为切点,将所有抑郁症患者分为MT高值组(51.3ng/L,n=43)与MT低值组(51.3ng/L,n=43),前者血清CRH、ACTH、COR均显著低于后者(t=3.330,3.315,2.314;P0.01,0.01,0.05);2血清MT水平与CRH、ACTH水平负相关(r=-0.414,-0.329;P0.01,0.05)。结论褪黑素对抑郁症患者的HPA轴功能可能有一定的抑制作用。     

松果体腺、褪黑素与抗应激作用

褪黑素呈典型的昼夜节律合成分泌 ,褪黑素激素水平的变化是 2 4h生物钟的探针。褪黑素合成分泌受光 /暗循环、视上核以及褪黑素合成过程中的底物血清素 (STN)、两个限速酶N 乙酰转移酶 (NAT)和羟吲哚 氧 甲基转移酶 (HIOMT)昼夜节律变化的调控 ;松果体腺内STN浓度戏剧性节律波动是由NAT浓度在昼夜间的较大波动所引起 (NAT夜间峰值是白昼低谷的 5 0 10 0倍 )。褪黑素的节律合成分泌与HPA轴所控制的激素 (ACTH和皮质醇 )所呈现昼夜节律性恰好相反 ,褪黑素可能与减少皮质激素分泌总量和增加糖皮质激素反馈调节敏感性有关 ;外源性褪黑素保护实验性糖尿病动物可能与抗氧化应激作用有关。     

外源性ADM对肾脏急性机械性损伤早期HPA轴的影响

目的: 研究外源性肾上腺髓质素(ADM)的运用对肾脏急性机械性损伤早期下丘脑-垂体-肾上腺皮质(HPA)轴的影响,探讨外源性ADM在急性创伤中的生物学作用。方法: 健康成年普通级Wistar大鼠104只,随机分为4组:正常对照组(8只)、单纯创伤组(32只)、伤前给药组(32只)、伤后给药组(32只);后3组采用自由落体打击仪直接打击大鼠脊肋区制作肾脏机械性损伤模型。2个给药组分别于损伤前后10 min腹腔注射ADM(0.1 nmol/kg)。3 组肾损伤大鼠分为4 批分别于创伤后1、6、12、24 h采用快速心脏采血法处死。迅速解剖动物提取下丘脑标本,采用免疫组化染色法检测促肾上腺皮质激素释放激素(CRH)在下丘脑的表达;放免分析法检测血浆促肾上腺皮质激素(ACTH)、皮质醇(CORT)浓度。结果: 单纯创伤组下丘脑CRH的表达及血浆ACTH、CORT浓度较正常对照组轻微升高,但无显著差异;创伤前注射ADM使创伤后下丘脑CRH的表达在1、24 h,血浆ACTH浓度在12 h,以及血浆CORT浓度在6、12、24 h显著高于单纯创伤组及正常对照组(P<0.05);创伤后注射ADM使下丘脑CRH的表达在1、6、12 h,以及血浆CORT浓度在12、24 h明显高于单纯创伤组及正常对照组(P<0.05)。结论: 外源性ADM可激活HPA轴,使HPA轴各个层面的活动增强,但不同层面对外源性ADM的反应性不同,创伤前、后注射ADM对HPA轴的影响不同。     

松果体褪黑素与下丘脑-垂体-肾上腺轴的相互作用

近年来很多学者发现松果体褪黑素(MLT)可以通过下丘脑垂体肾上腺轴(HPA)影响机体免疫功能,本文主要列举了松果体MLT对HPA轴三个水平调节的新发现和可能的机制,证实松果体MLT对垂体和肾上腺皮质有明显的调节作用,但对下丘脑是否有调节作用还存在诸多争议,同时也简述了HPA轴对松果体MLT影响研究的新进展,提示二者实际上存在着昏综复杂的相互作用。     

松果腺对辐射免疫兴奋效应调节作用的研究

目的和方法：观察75mGYX射线全身照射去松果腺昆明系雄性小鼠,血清皮质酮,脾和胸腺细胞免疫功能变化及体内、外给予褪黑素对其免疫功能的影响。结果：去松果腺小鼠经75mGyX射线全身照射后,血清皮质酮水平显著升高,脾细胞对ConA反应性和胸腺细胞自发增殖能力明显降低,体内注入褪黑素或体外培养细胞加人褪黑素可使因去松果腺免疫功能降低而重新升高。结论：松果腺褪黑素对低剂量辐射引起的免疫兴奋效应有调节作用。     

难治性抑郁症患者甲状腺激素水平动态分析

目前有研究发现,抑郁症患者下丘脑-垂体-肾上腺轴（HPA轴）存在功能亢进,而下丘脑-垂体-甲状腺轴（HPT轴）功能低下,主要表现为血浆皮质醇浓度增高,促肾上腺皮质激素（ACTH）分泌增强以及促甲状腺释放激素（TRH）兴奋试验迟钝等[1],难治性抑郁症患者的HPA和HPT轴的损害更严重[2]。本文主要对难治性抑郁症患者的甲状腺激素水平进行动态测定,探讨抑郁症与甲状腺激素水平的变化情况。     

下丘脑-垂体-肾上腺轴紊乱对焦虑性抑郁模型大鼠海马结构的影响

目的研究下丘脑-垂体-肾上腺(HPA)轴紊乱对焦虑性抑郁模型大鼠海马结构的影响,探讨焦虑性抑郁的潜在发病机制。方法将大鼠随机分为空白组、溶媒组、焦虑组、抑郁组和焦虑性抑郁组,每组12只。采用慢性束缚应激联合皮质酮注射方法建立焦虑性抑郁大鼠模型,连续21 d;造模后采用高架十字迷宫(EPM)、旷场实验(OFT)、强迫游泳实验(FST)评价大鼠焦虑和抑郁样行为;HE染色检测大鼠HPA轴各组织及海马病理变化;ELISA检测大鼠血浆中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量;Western blot检测大鼠海马糖皮质激素受体(GR)蛋白表达。结果焦虑性抑郁组大鼠进入开臂的时间、次数及自主活动次数均与焦虑组相当,不动时间显著增加,与对照组及抑郁组比较有显著差异(P0.01或P0.05);HPA轴各组织均出现不同程度损伤,海马神经元肿胀,呈空泡状;同时,血浆中CRH、ACTH和CORT含量显著增加(P0.01或P0.05),海马GR表达显著下降。结论焦虑性抑郁模型组大鼠具有显著的焦虑及抑郁样行为,其发病机制可能与机体HPA轴紊乱及其引发的脑内海马损伤密切相关。     

海洛因依赖者急性戒断前后下丘脑-垂体-肾上腺轴功能紊乱的研究

目的:探讨海洛因依赖者急性戒断前后下丘脑-垂体-肾上腺轴(HPAA)功能紊乱的原因。方法:放射免疫法(RIA)测定30例海洛因依赖者戒毒前、后不同时间点及13例正常人血浆细胞因子(IL-1β、TNF-α、IL-2)及肽类激素(ACTH、CORT、β-EP)含量,并对其进行相关性分析。结果:在未戒断时,IL-1β与CORT有显著负相关;而在戒断7天时,呈现TNF-α与ACTH显著正相关,此时ACTH对CORT的影响较大;到了戒断14天时,IL-1β与ACTH出现显著负相关。结论:IL-1β、TNF-α对海洛因依赖者急性戒断前后HPA轴功能紊乱起着重要作用,同时也不能忽略β-EP及吗啡的作用。     

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.