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.     

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响

目的研究以腺苷A1 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30minPG、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A1 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受体触发大鼠心脏预处理延迟效应与Mn-SOD表达的关系

目的探讨以腺苷A1受体激动剂诱导大鼠心脏缺血预处理的延迟效应与超氧化物歧化酶(SOD)表达的关系.方法大鼠随机分6组,B组以腺苷A1受体激动剂CCPA预处理,24 h后制成离体心脏,低温缺血3 h,复灌1 h.观测心功能、SOD等.A组为缺血对照;C、E、F组在预处理前分别静注Mn-SOD反义、意义、错配寡核苷酸(ODN).结果B、C组左室压力上升最大速率恢复率(%)分别为72.62±16.28,50.00±17.02、Mn-SOD活性(IU/mg.prot.)分别为67.81±19.12,35.70±15.02,B组都高于C组,差异有显著性(P＜0.05).结论以腺苷A1受体激动剂诱导预处理的延迟保护与Mn-SOD的高表达有关.     

腺苷受体激动剂延迟预处理与核转录因子-κB的关系

目的了解以腺苷A1 受体激动剂 (PIA)延迟预处理与核转录因子(NF -κB)的关系。方法大白兔随机分3组。A组 :以PIA预处理 ;K组 :除抑制NF-κB外同A组 ;C组 :对照。24h后建立离体心脏模型,观察心功能和ATP等。结果缺血 -复灌后A组心功能恢复率、ATP含量高于C、K组 ,差异均有显著性 (P<0.05或P<0.01),而K组与C组差异无显著性。结论在以PIA延迟预处理中 ,NF-κB可能起着信号传导作用。     

腺苷A1受体诱导的心脏预处理与E-选择素和黏附分子-1表达的关系

目的了解腺苷A1受体能否诱导大鼠心脏预处理的延迟保护效应以及与其缺血-再灌注过程中心脏E-选择素(E-Selectin)和黏附分子-1(ICAM-1)表达的关系.方法雄性Wistar大鼠随机分为正常对照组(Z)、缺血对照组(C)、腺苷A1受体激动剂预处理组(A).离体心脏低温缺血180 min、复灌60 min.观察左室压力变化最大速率恢复率、心肌同功酶漏出活性,并以原位杂交或逆转录-PCR技术观察E-Selectin、ICAM-l表达水平.结果 A组左室压力变化最大速率恢复率明显高于C组(P＜0.05),心肌同功酶漏出活性明显低于C组(P＜0.05).A组E-Selectin、ICAM-l表达水平虽然高于Z组,但明显低于C组,差异有显著性(P＜0.01).结论腺苷A1受体可诱导大鼠心脏预处理的延迟保护效应,同时下调心脏E-Selectin、ICAM-l的表达.     

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。     

腺苷A1受体拮抗剂对L—NAME预处理第二窗心肌保护作用的影响

目的探讨药物L—NAME预处理后第二窗心肌保护作用是否与腺苷A1受体激活有关。方法将30只SD大鼠随机分成3组,每组10只,即缺血对照组、L—NAME预处理组及拮抗剂组,每组均于给药后24h建立离体大鼠心脏Langendorff灌注模型,全心缺血60min,再灌注120min,于S15、R1、R60、R1204个时间点观察HR、LVDP、CF的变化,检测冠脉流出液中cTnI的变化,电镜观察缺血后心肌的超微结构改变。结果全组心率缺血前无差别,拮抗剂组缺血后心率较L—NAME组慢,两者差异有统计学意义（P〈0．05）,与缺血对照组无差别;拮抗剂组的LVDP较L—NAME预处理组低,两者差异有统计学意义（P〈0．05）。与缺血对照组无差别;拮抗剂组的CF较L—NAME预处理组少,两者差异有统计学意义（P〈0．05）,与缺血对照组无差别：拮抗剂组的cTnI较L-NAME预处理组显著增高（P〈0．05）,与缺血对照组无差别;电镜下拈抗剂组及缺血对照组心肌超微结构的损伤程度较L—NAME预处理组重。结论腺苷A1受体拮抗剂DPCPX阻断了L—NAME预处理第二窗的心肌保护作用,腺苷A1受体可能是L-NAME预处理引起心肌保护作用的启动因子。     

缺血低氧对大鼠心肌产生血管内皮生长因子的影响及其意义

目的:了解缺血低氧刺激与大鼠心肌血管内皮生长因子(VEGF)产生的关系、意义及其可能机制。方法:1.建立Wistar大鼠急性心肌梗塞模型,将28只大鼠随机分为4组,每组7只:A组正常对照;B组急性心肌梗塞1d;C组急性心肌梗塞3d;D组急性心肌梗塞7d。心肌冰冻切片,免疫组化探测VEGF。2.原代培养大鼠心肌细胞随机分组:单纯缺氧组,A:缺氧培养0h;B:缺氧培养6h;C:缺氧培养12h;D:缺氧培养24h;蛋白激酶C(PKC)激动剂波佛酯(PMA)组,A:加入PMA0ng/mL;B:加入PMA10ng/mL;C:加入PMA100ng/mL;D:加入PMA1000ng/mL;均缺氧培养24h;PKC抑制剂chelerythrine(CT)组,A:加入CT0nmol/L;B:加入CT10nmol/L;均缺氧培养24h。免疫组化测定培养心肌细胞中血管内皮生长因子(VEGF),经计算机扫描,图像分析定量。结果:随缺血低氧时间延长,心肌产生VEGF增加,与对照组比较各组均有显著差异,缺血低氧时间与VEGF产生量呈正相关。不同剂量PMA与chelerythrine分别增强及减弱VEGF在缺氧心肌细胞中的表达。结论:缺血低氧强烈刺激心肌产生血管内皮生长因子,缺血心肌通过分泌VEGF对自身具有重要的保护意义。其信号转导途径部分是通过PKC通路实现的。     

前列地尔预处理对大鼠心肌缺血再灌注损伤的保护性作用

目的本实验采用酶组织化学法观察前列地尔预处理对大鼠心肌缺血再灌注损伤是否有保护性,并探讨其可能机理。方法选用275±25g的SD雄性大白鼠,随机分为6组,每组8只。假手术对照组(A),心肌缺血再灌注模型组(B),经典缺血预处理组(C),前列地尔脂肪乳剂早期保护组(D),前列地尔脂肪乳剂延迟保护组(E),前列地尔脂肪乳剂在缺血前72h应用组(F)。采用酶组织化学方法观察心肌过氧化氢酶及琥珀酸脱氢酶表达。结果与模型组相比,经典缺血预处理组、前列地尔预处理早期保护组及延迟保护组心肌过氧化氢酶及琥珀酸脱氢酶明显升高(p<0.05),且早期保护作用强于延迟作用。结论前列地尔预处理对大鼠心肌损伤具有早期和延迟保护作用。     

前列地尔预处理对大鼠心肌缺血再灌注损伤的心脏超微结构的保护作用

目的　观察比较前列地尔预处理及经典缺血预处理对在体大鼠缺血 /再灌注心肌损伤的保护效应。方法　动物分为假手术对照组、缺血再灌注组、经典缺血预处理组、前列地尔预处理早期保护组及延迟保护组 ,透射电镜观察心肌超微结构的变化 ,同时用黄嘌呤氧化酶法测定心肌组织的超氧化物歧化酶 (SOD)活性和用硫代巴妥酸法测定丙二醛 (MDA)含量。结果　前列地尔预处理及经典缺血预处理均有保护心肌超微结构和抗氧化效应 ,与模型组相比 ,经典缺血预处理组、前列地尔预处理早期保护组及延迟保护组明显降低缺血再灌注后的心肌MDA含量 (P<0 .0 5 和升高T SOD (P<0 .0 5 水平。结论　前列地尔预处理对在体大鼠缺血 /再灌注心肌损伤具有保护效应 ,能模拟经典缺血预处理心肌保护效应。     

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.