糖尿病大鼠心肌病理变化及脂质过氧化和一氧化氮的改变

目的：研究糖尿病心肌的病理变化及其发生机制。方法：用光镜及透射电镜观察四氧嘧啶诱导的糖尿病1个月大鼠心肌形学改变,并测定心肌细胞超氧化物歧化酶（SOD）、谷膛甘肽过氧化物酶（GSH－Px)、一氧化氮合酶（NOS）的活性及一氧化氮（NO）、丙二醛（MDA）含量。结果：光镜下见心肌细胞萎缩、嗜酸性变及空泡变性,间质纤维增生,透射电镜下见线粒体扩张、嵴变短,内质网扩张,骨原纤维破坏,间质胶原纤维增生。SOD、GSH－Px活性下降,NOS活性及NO、MDA含量增加。结论：糖尿病大鼠心肌病变主要为心肌萎缩、线粒体扩张及肌原纤维破坏,间质纤维增生,脂质过氧化作用及NO所致的损伤可参与其中。     

脑缺血预处理对大鼠海马CA1区一氧化氮合酶活性和一氧化氮含量的影响

目的：观察脑缺血预处理（CIP）后大鼠海马一氧化氮合酶（NOS）活性和一氧化氮（NO）含量的变化，探讨NO在脑缺血耐受（BIT）诱导中的作用。 方法： 将140只凝闭双侧椎动脉的Wistar大鼠分为sham、CIP组、损伤性缺血组和CIP＋损伤性缺血组。夹闭双侧颈总动脉致全脑缺血3 min作为CIP，10 min作为损伤性缺血，第4组中CIP与损伤性缺血之间间隔3 d。所有动物均于末次脑缺血恢复再灌注后0 h、2 h、16 h、24 h、36 h、72 h和7 d（每个时点n=5）取海马CA1区脑组织，分光光度法检测NOS活性，硝酸还原酶法检测NO2-/NO3-含量。 结果： CIP组NOS活性和NO2-/NO3-含量于再灌注后16 h开始升高，24 h达高峰，接近sham组的1.5倍，36 h降至基础水平，其升高的持续时间短于BIT诱导的时程（1-7 d）；损伤性缺血组NOS活性和NO2-/NO3-含量的变化趋势与CIP组类似，但其峰值（24 h）超过sham组的2倍，显著大于CIP组（P<0.05）；CIP+损伤性缺血组NOS活性和NO2-/NO3-含量亦有一定程度的升高，但其峰值（24 h）明显低于损伤性缺血组(P<0.05)。 结论： CIP引起NOS活性及NO2-/NO3-含量的适度增加，参与BIT的诱导；同时CIP阻止损伤性缺血后NO的过量生成所致的细胞毒性作用可能是其诱导BIT的另一途径。     

银杏叶提取物对糖尿病大鼠附睾组织活性氧的影响

目的 探讨银杏叶提取物（EGb）对糖尿病大鼠附睾组织活性氧的影响。方法 Wistar雄性大鼠40只，随机分成3组，对照组（C），糖尿病组（DM组）和银杏叶（EGb）治疗组。应用链脲佐菌素（Streptozocin STZ）加高脂高糖饮食制备2型糖尿病模型，治疗组同时给予银杏叶提取物（EGb）10周后，取双侧附睾组织，检测组织中MDA含量、NO含量和SOD、GSH—Px、NOS活性。结果 2型糖尿病模型制备成功，糖尿病组与对照组比较。SOD、GSH—Px活性显著降低（P〈0.01），MDA含量和NO含量及NOS活性明显高于对照组（P〈0.01），而治疗组与糖尿病组比较，SOD、GSH—Px活性显著升高（P〈0．01），MDA含量和NO含量及NOS活性明显低于糖尿病组（P〈0.01）。结论 银杏叶提取物对糖尿病大鼠附睾组织具有保护作用。     

NG-硝基-L-精氨酸对大鼠内毒素性肺线粒体损伤的影响

目的： 观察非选择性一氧化氮合酶(NOS)抑制剂NG-硝基-L-精氨酸(L-NA)对急性肺损伤大鼠肺线粒体功能的影响，并探讨其改善急性肺损伤的作用机制。方法: 将SD大鼠随机分为空白对照组、急性肺损伤组、L-NA治疗组，采用舌静脉注射脂多糖(LPS)复制大鼠急性肺损伤模型，于大鼠急性肺损伤3h后给L-NA治疗3h，断头放血处死大鼠，迅速取出肺脏，匀浆器混匀后，低温差速离心法提取肺线粒体，测定线粒体总ATP酶、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、总一氧化氮合酶（T-NOS）、诱生型一氧化氮合酶（iNOS）、结构型一氧化氮合酶（cNOS）的活性，以及线粒体肿胀度、膜流动性和线粒体一氧化氮（NO）、丙二醛（MDA）含量；电镜观察大鼠肺线粒体超微结构的改变及治疗药对此改变的影响。结果: 在大鼠内毒素性急性肺损伤后，肺脏组织中线粒体表现为肿胀、膜流动性降低，线粒体中的T-NOS和iNOS活性显著升高，线粒体NO生成明显增加，而cNOS活性无明显变化；线粒体总ATP酶、SOD、GSH-Px活性均明显下降，线粒体MDA含量明显升高。急性肺损伤3h给予L-NA治疗3h,与急性肺损伤组相比，一氧化氮合酶活性有所改变，NO生成显著下降，总ATP酶、SOD、GSH-Px活性均显著升高，MDA含量下降。电镜结果显示内毒素性急性肺损伤后肺脏组织细胞水肿，线粒体肿胀、嵴断裂、溶解、消失；L-NA能改善内毒素性急性肺损伤引起的细胞水肿、线粒体肿胀和空泡化。结论: L-NA能明显抑制急性肺损伤后线粒体一氧化氮合酶活性，减少NO生成，改善线粒体能量供应，增加线粒体抗氧化作用，从而减轻急性肺损伤。     

四逆汤对缺血-再灌注离体鼠肺的保护作用

目的： 建立离体大鼠肺灌流模型，研究四逆汤（SND）对缺血-再灌注肺的保护作用及可能机制。方法：将SD大鼠随机分成假手术组、模型组和模型+SND组，观察SND对大鼠肺组织形态学改变、平均肺动脉压（MPAP）、肺组织湿/干重比（W/D）、灌流液及肺组织匀浆中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量以及肺组织匀浆中一氧化氮（NO）含量和一氧化氮合酶（NOS）活力的影响。结果：模型+SND组的肺泡壁增厚程度和肺泡水肿程度显著低于模型组，肺组织W/D值及MPAP显著小于模型组，灌流液和肺组织匀浆中SOD活性显著高于模型组，而MDA含量显著低于模型组。SND可显著抑制缺血-再灌注引起的肺组织NO含量的减少。但3组间比较，NOS含量无显著差异。结论：SND有抗大鼠肺缺血-再灌注损伤作用，其机制可能与清除氧自由基和改善组织灌流有关。     

一氧化氮与氧自由基在大鼠急性乙醇性胃粘膜损伤中的作用

目的：研究大鼠乙醇性急性胃粘膜损伤中，一氧化氮（NO）与氧自由基的作用及二者之间的关系，以探讨NO对急性胃粘膜损伤发挥保护作用的机制。方法：以酒精给大鼠灌胃制备急性胃粘膜损伤模型，应用NO合酶抑制剂（L-NAME）及NO前体L-精氨酸（L-Arg）按不同分组尾静脉注射。取门脉血测定NO和丙二醛（MDA）水平，并取出胃进行形态学观察。结果：酒精灌胃后，大鼠门脉血NO含量降低，MDA水平升高，胃粘膜损伤面积随酒精浓度升高而增加；尾静脉给予L-NAME后，NO含量进一步下降，而MDA量更为升高，粘膜损伤进一步加重；L-Arg与L-NAME合用后，NO和MDA含量均有所恢复，粘膜损伤也明显减轻。门脉血NO与MDA含量呈负相关关系。结论：氧自由基的大量生成是乙醇性急性胃粘膜损伤的重要发生机制之一。内源性NO能够清除氧自由基，改善胃粘膜微循环，减轻急性胃粘膜损伤程度，对胃粘膜有保护作用。     

RGDS肽对胶元活化的大鼠血小板L-Arginine/NO途径的影响

本工作在胶原活化的大鼠血小板上,观察RGDS肽对血小板聚集、L一精氨酸（L－Arg）转运、一氧化氮合酶（NOS）活性和亚硝酸盐（NO2－）含量的影响。结果发现,4μg／mL胶原引起血小板聚集时,L－Arg转运增强、NOS活性增高和NO2-含量增加。血小板L－Arg转运的Vmax与NOS活性和NO2-生成呈明显正相关（r=0.8100和0.8343,p＜0．01）;血小板聚集与NO2-生成亦呈明显正相关（r=0.7660,P＜0.05）。RGDS肽200μmol／L凡与胶原共同孵育,可明显抑制胶原引起的血小板聚集、L－Arg转运增强、NOS活性增高和NO2-含量增加。提示,胶原激活的血小板L－Arg／NO途径增加是通过Ⅱb／Ⅲa复合物所介导,RGDS肽可括抗其增加作用。     

氧化应激对体外神经元一氧化氮释放量的影响

目的：探讨氧化应激对神经元产生一氧化氮（NO）的影响及其NO对神经元的作用机理。方法：对分离培养的新生SD大鼠大脑皮质神经细胞分别进行缺氧、低浓度H₂O₂、缺氧+超氧化物歧化酶（SOD）和H₂O₂+SOD处理,用比色法检测培养上清液中NO、丙二醛（MDA）含量和乳酸脱氢酶（LDH）、SOD活性。结果：与对照组比较,缺氧组和H₂O₂组的NO、LDH、MDA含量均显著高于对照组,SOD活性显著低于对照组,NO含量与SOD活性变化呈负相关。预先给予终浓度为200×10³U/L的SOD,然后再对分离培养的神经细胞进行缺氧、低浓度H₂O₂处理,可使神经细胞的NO、LDH和MDA释放量明显减少,各组间NO含量与LDH、MDA含量呈正相关。结论：氧化应激使神经元NO产生增多,NO与氧自由基对神经细胞的损伤有联同作用。SOD具有清除氧自由基和减轻NO对神经元的损伤作用。     

银杏叶提取物对糖尿病大鼠脂代谢及巨噬细胞功能的影响

目的： 研究银杏叶提取物（EGb）对2型糖尿病大鼠脂代谢及巨噬细胞功能的影响。 方法： SD大鼠分4组：正常对照组、高脂组、糖尿病组、EGb治疗组，治疗结束取血测血糖、血脂、血胰岛素并分别灌取4组大鼠腹腔及肺泡巨噬细胞，测定巨噬细胞内超氧化物歧化酶（SOD）、一氧化氮（NO）及丙二醛（MDA）的水平，并用RT-PCR方法测定大鼠肺泡巨噬细胞内CD36、PPARγ的基因表达水平。 结果： 糖尿病大鼠血糖、血胰岛素、总胆固醇（TC）、总甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）升高，经EGb治疗后，血糖、血胰岛素、TC、TG、LDL-C明显降低；糖尿病大鼠腹腔及肺泡巨噬细胞内SOD活性下降、NO及MDA含量增高，经EGb治疗后，SOD活性升高、NO2-/NO3-及MDA含量下降；糖尿病大鼠肺泡巨噬细胞CD36基因表达升高，PPARγ基因表达升高，经EGb治疗后，CD36基因表达继续升高但无显著差异、PPARγ基因表达继续升高。 结论： EGb对糖尿病大鼠巨噬细胞脂质过氧化有较好的拮抗作用，并能降低一氧化氮含量，从而改善糖尿病时巨噬细胞功能；EGb可提高2型糖尿病大鼠肺泡巨噬细胞CD36、PPARγ基因的表达水平，这可能是其降血脂和改善胰岛素抵抗的机制之一。     

一氧化氮途径对大鼠精子发生的影响

为阐明一氧化氮途径对精子发生的影响 ,探讨一氧化氮对精子发生的调节作用 ,将雄性SD大鼠分为 4组 ,分别于腹腔内注射左旋精氨酸 (L arginine ,L ARG)、N 硝基左旋精氨酸甲酯 (N nitro L arginine mythel ester,L NAME)、L ARG +L NAME与生理盐水 ,每天一次 ,共 1 2d。于最后一次注射后 2h采血并处死动物。放免法测定血清内睾酮含量 ;GREISS法测定血清NO-x (硝酸盐 亚硝酸盐 )含量 ;常规组织学切片观察生精上皮形态 ,并对Ⅶ -Ⅷ期生精上皮横断面的各级生精细胞进行定量分析 ;扫描电镜观察生精小管内精子密度。结果表明 :L ARG组血清内NO-x 含量高于对照组 (P <0 0 1 ) ,睾酮含量低于对照组 (P <0 0 1 ) ,精子生成减少 (P <0 0 1 ) ;L NAME组血清内NO-x 含量低于对照组 (P <0 0 1 ) ,睾酮含量高于对照组 (P <0 0 1 ) ,精子生成增加 (P <0 0 1 )。L ARG +L NAME组NO-x 与睾酮含量及精子的生成无显著性变化。因此 ,加强NO途径抑制精子发生 ,抑制NO途径促进精子形成     

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.