Zn~(2+)预处理对离体大鼠缺血再灌注损伤心肌的保护作用

目的 :观察Zn2 + 预处理诱导金属硫蛋白 (MT)在心肌细胞的表达及对离体大鼠缺血再灌注损伤心肌的保护作用。方法 :3 2只Sprague Dawley大鼠随机分为对照组及实验组 ,实验组按腹腔注射ZnSO4 到建立再灌注模型的时间分为E1 2h,E2 4h及E4 8h组 ,每组各 8只。检测LDH ,CK、ATP含量及心功能指标 (LVSP与±dp/dtmax) ,用1 0 9Cd/血红素饱和法测量心肌组织中金属硫蛋白的含量。结果 :E2 4h及E4 8h组MT表达量较对照组高 (P <0 .0 1) ,E1 2h组虽有表达 ,但其与对照组间差异无显著性。E2 4h及E4 8h组LDH与CK较其它二组低 ,而ATP较其它二组高 ,心功能指标较其它二组改善。E1 2h组及对照组之间相应各指标 (LDH ,CK、ATP、LVSP与±dp/dtmax)间差异无显著性 (P >0 .0 5 )。结论 :Zn2 + 预处理可诱导MT在心肌细胞的表达而对离体大鼠缺血再灌注损伤心肌具有保护作用。     

钙预处理对离体大鼠缺血再灌注心肌细胞的保护作用

目的 :研究钙预处理是否对缺血再灌注心肌有保护作用 ,其作用是否通过蛋白激酶C(ProteinKinaseC ,PKC)及线粒体ATP依赖性钾通道 (KATP)起作用。方法 :3 2只SD大鼠 ,随机分为 4组 :缺血再灌注组 (I/R组 )、钙预处理组 (CPC组 )、钙预处理加PKC阻滞剂Chelerythine组 (CLT组 )、钙预处理加线粒体KATP通道阻滞剂 5 hy droxydecanoate组 (5 HD组 ) ,分别检测LDH及CK的漏出量、心肌ATP含量、心功能指标 (LVSP及±dp/dtmax)。 结果 :与I/R组比较 ,CPC组CK、LDH漏出量明显减少 (P <0 .0 1) ,心肌ATP含量增加 (P <0 .0 1) ,心功能改善 ;CLT组及 5 HD组上述各指标 (LDH、CK、ATP、LVSP及±dp/dtmax)分别与I/R组相同指标之间无显著性差异 (P >0 .0 5 )。结论 :钙预处理对I/R心肌有保护作用 ,其保护作用可被PKC阻滞剂及KATP阻滞剂所取消 ,提示其保护作用可能通过PKC途径及线粒体KATP通道起作用     

钙敏感受体在大鼠心肌缺血/再灌注损伤的表达变化及与心肌损伤关系

目的： 观察钙敏感受体（CaSR）在大鼠心肌缺血/再灌注时的表达变化，揭示其与心肌缺血/再灌注损伤的关系。方法： Wistar大鼠随机分为5组：假手术组（sham组）、缺血再灌注1、2、4和6 h组（I/R 1 h、2 h、4 h、6 h组）。采用冠状动脉结扎和松结的方法，复制大鼠在体心肌缺血/再灌注损伤模型，记录左室收缩压（LVSP）和左室内压最大变化速率（±dp/dtmax），测定血清LDH、SOD活性和MDA含量，透射电镜观察心肌超微结构变化， RT-PCR法检测心肌组织中CaSR mRNA的表达变化。结果：LVSP、左室内压±dp/dtmax及SOD活性随再灌注时间延长而减低，LDH活性和MDA含量在再灌注2 h时最高；心肌超微结构损伤在再灌注1 h、2 h较重，随再灌注时间延长而减轻；大鼠心肌缺血/再灌注1 h、2 h心肌组织CaSR的mRNA表达升高，再灌注4 h、6 h后降低。结论： CaSR mRNA表达多时心肌损伤较重，CaSR可能参与了心肌缺血/再灌注损伤。     

热休克蛋白70对未成熟心肌细胞功能的影响

目的探讨热休克蛋白70(HSP70)对未成熟心肌细胞功能的影响。方法健康新生长耳大白兔随机分为2组。对照组(C):腹腔注射生理盐水0.4ml,注射后24h取离体心脏,常规建立Langendorff离体心脏灌注模型,灌注15min转为工作心15min后停灌45min,恢复灌注15min改为工作心30min。实验组(E):腹腔注射重酒石酸去甲肾上腺素,24h后取离体心脏,方法同对照组。测定心肌细胞中HSP70含量及相关生化指标并作统计学处理比较。结果HSP70含量E组明显高于C组;E组ATP含量、SOD活性方面均优于C组(P<0.01),MDA含量、CK、LDH漏出率方面均低于C组(P<0.01),心肌线粒体Ca2+-ATPase活性、[ATP]m均优于C组(P<0.01),心肌细胞内Ca2+含量、心肌线粒体Ca2+含量低于C组(P<0.01)。结论HSP70对缺血再灌注未成熟心肌细胞功能具有明显的保护作用。     

11，12-EET的延迟性心脏保护作用与磷酸化ERK1/2的关系

目的:观察11，12-EET延迟性保护作用对缺血再灌注大鼠心肌ERK活性及磷酸化ERK表达的影响，探讨其在11，12-EET延迟性保护中的作用。 方法:复制大鼠心肌缺血/再灌注模型；观察缺血/再灌注期间心脏收缩期左心室内压上升的最大变化速率（+dp/dtmax）及舒张期左心室内压下降的最大变化速率（-dp/dtmax）；采用免疫共沉淀法测定大鼠心肌组织中细胞外调节激酶（ERK）的活性，采用Western blotting法测定大鼠心肌组织中磷酸化ERK的表达。 结果:I/R组缺血60 min及再灌注30 min两个时段±dp/dtmax均低于sham组（P<0.05），24 hEET+I/R组缺血60 min及再灌注30 min两个时段±dp/dtmax明显高于I/R组（P<0.05），而24hEET+PD+I/R组缺血60 min及再灌注30 min两个时段±dp/dtmax明显低于24hEET+I/R组（P<0.05）。ERK的活性24hEET+I/R高于normal组，24hEET+I/R组低于24hEET+PD+I/R组。磷酸化ERK的表达I/R组高于normal组和sham组，24hEET+I/R高于I/R组，24 hEET+I/R组低于24hEET+PD+I/R组。 结论:外源性11，12-EET具有延迟性心脏保护作用，大量激活磷酸化的ERK参与这种保护作用。     

热休克蛋白70对离体心脏心肌间质的保护作用

目的探讨热休克蛋白70（HSP70）对大鼠离体心脏心肌间质的影响。方法Wistar大鼠16只，分为2组：对照组（C，n=8），腹腔注射生理盐水0．4ml，24h后取离体心脏灌注HTK心脏保护液，4℃保存3h后建立Langendorff灌注模型，灌注KH液2h；实验组（E，n=8），腹腔注射重酒石酸去甲肾上腺素，24h后取离体心脏，方法同对照组。以心肌细胞中HSP70含量、血流动力学指标、心肌组织羟脯氨酸（HP）、内皮索（ET）含量和心肌超微结构等作为观察指标。结果HSP70含量E组与C组比较明显增高；E组心功能恢复方面优于C组（P〈0．05），HP含量优于C组（P〈0．01），ET含量低于C组（P〈0．01），心肌超微结构损伤较C组明显减轻。结论HSP 70对供心心肌间质具有保护作用。     

金属硫蛋白对缺血/再灌注未成熟心肌细胞功能的影响

目的探讨诱导金属硫蛋白(MT)在未成熟心肌中的表达对缺血/再灌注未成熟心肌细胞功能的影响.方法采用Langendorff离体灌注模型,大白兔分为4组:对照组(C,n=9),腹腔注射蒸馏水0.3ml,按注射后时间12、24、和48 h取离体心脏,灌注KH液15 min转为工作心15 min,全心停灌45min,恢复灌注15 min改为工作心30 min;E12h组(n=6)、E24h组(n=6)、E48h组(n=6)各组分别按腹腔注射3.6%ZnSO4(1.5 ml/kg)后12、24和48 h取离体心脏,常规建立Langendorff灌注模型.方法同C组.以心肌细胞中MT含量、CK和LDH漏出率、ATP含量、心肌细胞内Ca2 含量、心肌线粒体Ca2 -ATPase活性及其Ca2 含量、心肌线粒体合成ATP能力[ATP]m作为观察指标.结果腹腔注射ZnSO4后12 h MT开始表达,24h达高峰,48 h仍在高表达水平.MT含量在E24h、E48h组与C、E12h组比较明显增高;E24h、E485h组ATP含量优于C组和E12h组(P＜0.05),CK、LDH漏出率均低于C组和E12h组(P＜0.05),心肌线粒体Ca2 -ATPase活性、[ATP]m均优于C组和E12h组(P＜0.01),心肌细胞内Ca2 含量、心肌线粒体Ca2 含量低于C组和E12h组(P＜0.01).结论腹腔注射ZnSO4可诱导心肌MT长时间表达,MT可减轻未成熟心肌细胞缺血/再灌注损伤.     

ATP敏感性钾通道对腺苷受体诱导的心脏预处理延迟效应的影向

目的研究以腺苷A受体激动剂预处理的延迟保护效应与心肌三磷酸腺苷(ATP)敏感性钾通道的关系.方法Wistar大鼠随机分4组,其中PS、PG组以CCPA预处理,IC组仅注射CCPA溶剂,GC组不作CCPA预处理.24h后取出心脏,以改良Langendorff灌注装置制成离体心脏模型.缺血前30min PG、GC组先经主动脉灌注优降糖.平衡灌注后4℃改良St.Thomas心麻液诱导心脏停搏,维持12～15℃缺血180min..之后复灌37℃氧合平衡液60min.观察心功能、ATP等指标.结果在复灌60min时左室压力上升和下降最大速率恢复率(±dp/dtmax,%)及心肌ATP含量均高于PG、GC:、IC三组,差异都具有显著性(P＜0.01);PG、GC、IC组间无显著性差异(P＞0.05).结论以腺苷A受体激动剂预处理诱发大鼠心脏产生的延迟保护效应与心肌ATP敏感性钾通道开放有关.     

腺苷A1受体触发延迟预处理对兔心保存的实验研究

目的探讨腺苷A1 受体激动剂延迟预处理对供心的保护效果。方法大白兔以A1 受体激动剂PIA预处理24h后制成离体心脏,以4℃改良St.Thomas液诱导心脏停搏 ,再放入该液中低温保存4h ,再灌注1h。观察心功能恢复率、心肌ATP、CK -MB释放量。另设单纯改良St.Thomas液保存对照组。结果PIA预处理心功能恢复率 (+dp/dtmax % )为59.75±18.41 ,明显高于对照组 (38.18±13.92),差别有显著性 (P<0.05)。心肌ATP含量 (10-3μmol/wetg)PIA预处理组为4.08±1.34 ,明显高于对照组 (2.02±0.88) ,差异亦有显著性(P<0.01)。结论腺苷A1 受体激动剂延迟预处理能改善供心保存效果。     

糖尿病大鼠心肌磷酸受纳蛋白基因表达和肌浆网 Ca2+-ATPase活性的变化

目的：观察糖尿病(DM)大鼠心肌磷酸受纳蛋白（PLB）基因表达和肌浆网 Ca2+-ATPase活性的变化及其与心功能的关系。方法:复制糖尿病大鼠模型，分别于4、6、8周后对糖尿病组和对照组进行左心室血流动力学检测，测定心肌PLB mRNA转录水平以及蛋白表达水平变化，检测心肌肌浆网 Ca2+-ATPase活性。结果:糖尿病大鼠心肌PLB mRNA转录和蛋白表达水平4周时与正常大鼠无明显差异，6周时和8周时明显高于正常大鼠；肌浆网 Ca2+-ATPase活性4周时无明显改变，6周时和8周时明显低于正常大鼠；糖尿病大鼠4周时LVSP、LVEDP、±dp/dtmax与正常大鼠无明显差异，6周、8周时LVSP、±dp/dtmax显著降低，LVEDP显著升高。结论：糖尿病大鼠心肌PLB表达水平升高，肌浆网 Ca2+-ATPase活性降低，引起心功能下降。     

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.