谷氨酰胺对内毒素损伤的心肌的保护作用研究

目的:研究谷氨酰胺对内毒素损伤的心肌的保护作用研究。方法:取健康体重(250±30)gSD雄性大鼠22只随机分成3组, 正常对照组(n=7), 内毒素组(n=7), 谷氨酰胺+内毒素组(n=8), 在Langendorff装置上用Krebs-Henseleit(KH)液对大鼠离体心脏行主动脉逆灌。连续记录心肌细胞单相动作电位(MAP)、心肌收缩张力曲线, 在相应的时点分别测定冠脉流出液中的超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:谷氨酰胺组对内毒素损伤引起的心肌细胞单相动作电位幅度减小及D₂₀延长、心肌张力降低、心率变慢等变化有明显的改善作用, 同时可以明显逆转内毒素诱导的心肌SOD活性降低和MDA含量升高。结论:谷氨酰胺对内毒素损伤的心肌有明显的保护作用, 有机会成为一个有效防治内毒素性心肌损伤的药物。     

甘氨酸对内毒素所致心肌损伤的影响

目的探讨甘氨酸对内毒素所致心肌损伤的保护作用.方法采用Langendord装置,应用Krebs-Henseleit(KH)液行主动脉逆灌注,动态观察离体心脏单相动作电位(MAP)和心肌张力曲线,并在实验的0、20、50、80min收集灌流液,测定其中超氧化物歧化酶(SOD)、丙二醛(MDA)、乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)、一氧化氮(NO)等的含量.结果甘氨酸处理组对内毒素诱导心脏单相动作电位的D20、D50和心率等的变化有一定改善作用,但对心肌张力曲线的改善不明显,对内毒素诱导的SOD活性降低和MDA含量升高有抑制作用,可以减缓和降低心肌损伤引起的LDH和CK的释出,并且降低NO的释放等.结论甘氨酸可以减轻内毒素所致心肌损伤、改善心脏功能状态,其作用机制可能与甘氨酸拮抗内毒素的作用及甘氨酸对血管内皮细胞、心肌细胞的保护作用有关.     

甘氨酰谷氨酰胺在大鼠离体心脏缺血/再灌注损伤中的保护作用研究

目的： 研究甘氨酰谷氨酰胺对缺血再灌注大鼠离体心脏的保护作用。方法：应用Langendorff离体心脏灌注系统建立心肌缺血再灌注模型。30只SD雄性大鼠随机分为正常对照组(control)、甘氨酰谷氨酰胺对照组(Gly-Gln)、缺血再灌注组(I/R)、缺血/再灌注+甘氨酰谷氨酰胺组(I/R+ Gly-Gln)。I/R组及I/R+ Gly-Gln组分别灌注30 min后,全心停灌20 min,再灌注40 min,I/R+ Gly-Gln组于再灌注时在灌流液中加入Gly-Gln;正常对照组连续灌流90 min,Gly-Gln对照组灌流液中加入Gly-Gln。记录各组灌注时,左室舒张末压(LVEDP)、左室发展压(LVDP)、左室压力最大变化速率(±dp/dtmax)、心率(HR)及心肌细胞单相动作电位(MAP);同时在相应的时点分别测定冠脉流出液中的乳酸脱氢酶（LDH)、肌酸激酶(CK)活性。结果：离体大鼠心脏缺血20min,再灌注40 min,导致严重的心功能抑制,表现为LVEDP升高,LVDP、±dp/dtmax降低;再灌注液中加入Gly-Gln后,LVEDP降低,LVDP、±dp/dtmax明显升高（P<0.01)。I/R+ Gly-Gln组冠脉流出液中LDH、CK活性明显低于I/R组(均P<0.01)。结论： Gly-Gln能有效减轻缺血再灌注引起的左室功能下降,减少心肌细胞LDH、CK的释出,表明Gly-Gln对缺血再灌注损伤的大鼠离体心脏具有保护作用。     

甘氨酸抗心肌损伤作用及机制研究

目的 :研究甘氨酸抗心肌损伤的作用及机制。方法 :(1)取体重为 (2 5 0± 30 )g的雄性健康SD大鼠 2 2只 ,随机分成 3组 :正常对照组 (n =7) ,内毒素组 (n =7) ,甘氨酸 +内毒素组 (n =8) ,在Langendorff装置上用Krebs -Henseleit(KH)液对大鼠离体心脏行主动脉逆灌。连续记录心肌细胞单相动作电位 (MAP)、心肌收缩张力曲线 ;(2 )取健康成年雄性SD大鼠心脏做冰冻切片 ,分为 4组 :脊髓阴性对照组 (不含任何抗体的PBS)、脊髓阳性对照组 (一抗为抗甘氨酸受体组 )、心肌细胞阴性对照组、心肌细胞抗甘氨酸受体组。冰冻切片进行免疫组化荧光染色…     

热休克对大鼠再灌注性心律失常及心肌动作电位的影响

55只SD大鼠随机分为热休克组（H组，n=29)和对照组（Co组，n=26)。H组予以热休克预处理，Co组则否。两组先各取16只大鼠行Langendorff离体心脏灌注。以心电图记录模拟缺血后复灌时心律失常情况，并测定复灌时心脏流出液CK的活性，同时检测两组心脏组织中HSP70的含量和抗氧化酶的活性。接着对其余H组13只和Co且10只大鼠进行离体心脏乳头肌动作电位的测定。结果显示H组再灌注性心律失常明显减轻，心肌CK的释放量显著减少（P＜0．001）。同时H组心脏组织HSP70表达量显著增多，抗氧化酶活性也明显增强。H组台氏液灌流时心肌动作电位Vmax显著降低（P＜0．01）。以台氏液复灌后，心肌动作电位恢复时间也明显以H组为短。结果提示热休克预处理可以减轻大鼠心肌再灌注性损伤和再灌注性心律失常，此作用与心脏组织中HSP70含量的增加和抗氧化酶性的增强有关，同时还可能与热休克对心肌快Na^ 通道的抑制作用有关。     

非创伤性预处理在离体心脏抗再灌注损伤中作用机制的探讨

目的:观察非创伤性肢体缺血预处理对大鼠离体再灌注心肌是否有保护作用。方法:实验采用体重(250±30)gSD雄性大鼠25只随机分成3组,在Langendorff装置上对大鼠离体心脏进行灌流。对照组(C,n=8):在灌注全程均用富氧K-H液(充以95%O₂+5%CO₂),在恒压(8.33kPa)、恒温(37℃)条件下灌注;缺氧/复氧组(A,n=8):预灌15min后,灌注心脏先全心缺血缺氧15min,随后15min复氧再灌注(37℃);非创伤性肢体缺血预处理组(N-WIP,n=9):先将大鼠双后肢捆绑5min,松开5min,反复4次后,随后的方法同R组。在相应时点分别测定冠脉流出液和心肌匀浆中超氧化物歧化酶(SOD)活性,Ca²⁺-Mg²⁺-ATP酶活性和丙二醛(MDA)含量,同时记录心肌细胞的单相动作电位(MAP)和心肌收缩张力曲线。结果:非创伤性肢体缺血预处理能使再灌注心律失常发生率显著低于A组;心肌组织中MDA含量显著低于A组,心肌组织中SOD活性显著高于A组,心肌细胞的膜电位、Ca²⁺-Mg²⁺-ATP酶活性及肌张力较稳定。结论:非创伤性肢体缺血预处理对大鼠离体再灌注心肌有明显的保护作用,可能是通过增强心肌的抗氧化能力、稳定心肌Ca²⁺-Mg²⁺-ATP酶活性和膜相结构等途径,提高心肌细胞对再灌注损伤的抵抗力。     

耗竭心肌细胞内糖原对缺血后再灌注心肌的保护作用及其机制

本工作在离体大鼠等容收缩心脏模型上观察耗竭心脏细胞内糖原对心肌缺血再灌注损伤的影响。心脏富氧灌流30 min后,随机分为三组:Ⅰ、富氧组:富氧灌流75min。Ⅱ、对照组:常规K-H液富氧灌流15min,旷置30min,再灌流30min。Ⅲ、耗竭糖原组:先用充N_2(95%N_2:5%CO_2)的K-H液灌流15min,余同组Ⅱ。结果表明。耗竭心肌细胞内糖原可提高再灌注后心脏血液动力学的恢复;冠脉流出液中LDH活性及心肌组织MDA含量降低,线粒体及胞浆液中GSH-Px有较高的活性;心肌组织Na~+,Ca~(2+)超负荷减轻。说明耗竭心肌细胞内糖原可通过减少细胞内H~+的生成抑制Na~+/H~+交换,从而明显减轻心肌缺血再灌注损伤。     

葱白提取物预处理对心肌缺血再灌注损伤及相关生化因素的影响

目的:观察葱白提取物(FOB)预处理对大鼠离体心脏缺血再灌注损伤(MIRI)及相关生化指标的影响,探讨FOB抗MIRI的机制。方法:利用Langendorff建立大鼠离体心脏缺血再灌注(I/R)模型,观察左心室发展压(LVDP)恢复和再灌注痉挛度。用生化技术检测冠脉流出液中乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)活性和心肌细胞线粒体超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、ATP酶活性以及丙二醛(MDA)含量。结果:(1)FOB(25g/L、50g/L、100g/L)预处理对心肌I/R损伤后的LVDP恢复和再灌注痉挛度有明显改善作用,并随浓度增加,对心脏保护作用逐渐增强而加强,100g/LFOB预处理后的LVDP恢复和痉挛度的改善均接近正常组值(分别与I/R组和25g/LFOB组相比,均P<0.01;与50g/LFOB相比,均P<0.05),心脏恢复跳动更迅速,收缩和舒张规则有力;(2)FOB(25g/L、50g/L、100g/L)预处理明显降低LDH、CK活性和MDA含量,显著增加SOD、GSHPx、ATP酶活性,且随FOB浓度增高,上述作用更加明显,100g/LFOB预处理组各项生化指标与Control组无明显差异。结论:FOB预处理能有效保护MIRI,其机制与FOB减少心脏I/R时心肌细胞内Ca2+超载和抗脂质过氧化有密切关系。     

鱼腥草注射液抗内毒素性心肌损伤作用的实验研究

目的:揭示鱼腥草注射液抗内毒素诱导的心肌损伤作用的机制。方法:取SD雄性大鼠24只随机分成正常对照组(NC组,n=6),内毒素组(ET组,n=6),鱼腥草注射液+内毒素组(HHI+ET组,n=6)和单纯鱼腥草注射液组(HHI组,n=6),在Langendorff装置上用Krebs-Henseleit(KH)液对大鼠离体心脏行主动脉逆灌。在相应时点以HR、LVSP、LVEDP、LVDP、+dp/dt_max、-dp/dt_max等6项参数为指标,测定冠脉流出液中的超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及心肌组织一氧化氮(NO)含量、琥珀酸脱氢酶(SDH)活性。结果:与ET组相比,HHI+ET组在相应时点,左心室压差与心率乘积(LVSP-LVEDP)×HR、LVDP、+dp/dt_max恢复百分率明显改善,对内毒素诱导的心肌SOD、SDH活性的降低和MDA、NO含量的升高有明显抑制作用。结论:鱼腥草注射液具有明显的抗内毒素心肌损伤作用,通过降低心肌中NO的量,增强心肌的抗氧化能力,稳定心肌酶活性和膜相结构等途径,提高心肌对内毒素性损伤的抵抗力。     

钙激活钾通道在缺氧后处理对心肌保护的作用

目的： 探讨缺氧后处理在全心停灌缺氧模型中是否具有对抗心肌缺氧/复氧（A/R）损伤的作用，以及钙激活钾通道（KCa）和线粒体透性转换孔道（mPTP）是否参与缺氧后处理的抗心肌缺氧/复氧损伤。方法： 采用离体大鼠心脏Langendorff灌流模型，全心缺氧30 min、复氧120 min复制A/R模型。测定心室力学指标和复灌各时点冠脉流出液中乳酸脱氢酶（LDH）含量。实验结束测定心肌组织甲臜（formazan）含量。分离心肌线粒体，测定高钙诱导下mPTP的开放情况。结果： 缺氧后处理心肌细胞的formazan含量明显高于、而复灌期间冠脉流出液中LDH含量低于单纯A/R组，明显改善心室力学指标，缓解冠脉流量的减少。KCa通道阻断剂paxilline能明显阻断缺氧后处理的心肌保护作用。缺氧后处理心肌细胞的mPTP开放程度显著低于A/R组。结论： 缺氧后处理具有抗心脏缺氧/复氧损伤的作用，这种保护作用可能与其抑制KCa通道的开放和降低mPTP的开放有关。     

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.