α-亚麻酸在缺血性心衰中的保护作用及其对缺血早期炎症小体NLRP3的抑制作用

目的探讨α-亚麻酸(α-linolenic acid,ALA)在缺血性心衰中的保护作用及其对TNF-α、IL-6和炎症小体NLRP3(pyrin domain containing 3)等炎症介质的影响。方法通过结扎冠状动脉建立大鼠心肌梗死(myocardial infarction,MI)模型,给予ALA或其对照,监测MI后1周、2周和4周大鼠血清中TNF-α和IL-6炎症因子变化,检测MI后1周心肌组织中NLRP3相关蛋白及和MI后4周心脏功能的变化。结果与假手术组比较,血清中TNF-α和IL-6水平在MI后1周和2周均显著增加。MI后1周缺血区心肌组织中NLRP3表达显著增加,半胱氨酸蛋白酶1(cysteinyl aspartate specific protease-1,caspase-1)活性升高,IL-1β和TNF-α蛋白含量显著升高。补充ALA不仅显著降低大鼠MI后1周和2周血清中TNF-α和IL-6水平,而且减少MI后1周心肌组织中的NLRP3含量和caspase-1活性,进而降低了IL-1β和TNF-α含量,减少了中性粒细胞在心肌组织中的浸润,改善了MI 4周后的心脏功能。结论 MI前补充ALA可减少MI后1周炎症小体NLRP3相关蛋白表达,抑制TNF-α、IL-1β及IL-6炎症因子的生成,改善MI 4周后的心脏功能,延缓缺血性心衰的发生发展。     

Ghrelin对急性心肌梗死后大鼠心脏神经重构的影响及炎性因子的作用

目的:探讨Ghrelin对心肌梗死(MI)后大鼠神经重构的影响及其作用机制。方法:55只SD大鼠分为假手术组(Sham组)、急性心肌梗死(AMI)模型对照组(Control组)和Ghrelin干预组(Ghrelin组)。结扎冠状动脉制作AMI模型40只,Ghrelin组和Control组各20只,Ghrelin组于手术当天给予Ghrelin皮下注射,剂量为100μg/kg,2次/天;Sham组和Control组等量生理盐水作相同部位注射。四周后处死动物。检测梗死及非梗死区左室神经生长因子相关蛋白-43(GAP-43)、酪氨酸羟化酶(TH)、炎症介质白介素-1β(IL-1β),肿瘤坏死因子-α(TNF-α)和内皮素-1(ET-1)的表达。结果:与Control组相比,Ghrelin组梗死区及非梗死区GAP-43及TH的阳性表达明显减少,同时IL-1β、TNF-α和ET-1mRNA表达也明显受抑。结论:Ghrelin干预能够抑制大鼠MI后神经增生;炎性因子可能参与其中。     

大鼠急性心肌梗死心室重塑中细胞因子与胶原的变化

目的:探讨大鼠急性心肌梗死（MI）后心室重塑过程细胞因子与胶原分子的关系。 方法:制备雄性Wistar大鼠心肌梗死和假手术对照模型，于手术后3 d、1 w、4 w分别观察不同时点梗死区和非梗死区的Ⅰ、Ⅲ型胶原及炎症因子的mRNA变化。 结果:心肌梗死后第3 d胶原（Ⅰ、Ⅲ型胶原）和细胞因子（TGF-β1、TNF-α）皆上升，梗死区Ⅰ、Ⅲ型胶原在第4周仍然比非梗死区为高，TGF-β1、TNF-α在第1周达到高峰后逐渐下降但仍高于同期假手术组（P＜0.01），相关性分析提示梗死区和非梗死区TGF-β1、TNF-α均与Ⅰ、Ⅲ型胶原存在相关（P<0.01）。 结论:炎症因子参与心室重塑的病理生理过程，干预细胞因子可能作为早期防治心室重塑的手段。     

Ghrelin抑制大鼠心肌梗死后心室重构

目的:探讨Ghrelin对大鼠心肌梗死后心室重构的影响及其机制。方法:结扎SD大鼠前降支造成急性心肌梗死(AMI)模型,并设假手术组。结扎24h后,存活大鼠给予Ghrelin(100μg/kg)或生理盐水皮下注射,每天两次。4周后,超声心动图和血流动力学方法检测心功能,实时定量PCR检测梗死心肌白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)mRNA表达,Western-blot检测核转录因子-κB(NF-κB)活性。结果:与假手术组相比,AMI模型组左室收缩内径(LVESD)、左室舒张内径(LVEDD)、左室舒张末压力(LVEDP)都明显增加(P<0.01);而左室收缩压(LVSP)、压力变化值最大值(dp/dtmax)、左室短轴缩短率(FS)都显著降低(P<0.01)。与AMI模型组相比,Ghrelin治疗组LVEDP、LVEDD以及LVESD明显变小(P<0.01),而dp/dtmax及FS显著增加(P<0.01)。梗死后心肌IL-1β、TNF-αmRNA表达增强,Ghrelin治疗后IL-1β、TNF-αmRNA表达明显降低(P<0.01)。AMI模型组心肌核蛋白P65表达明显增加,而胞浆蛋白I-κBα含量显著减少(P<0.01),Ghrelin治疗明显降低梗死心肌核蛋白P65表达(P<0.01),同时增加胞浆蛋白I-κBα含量(P<0.01)。结论:Ghrelin能够抑制心肌梗死后心室重构,改善心功能,可能与其抑制炎症介质表达及NF-κB活性有关。     

压力负荷大鼠心肌重构与TNF-α和IL-10表达的动态相关性研究

目的:动态观察压力负荷增高致大鼠心肌重构发生发展过程中TNF-α和IL-10在心肌组织中表达的变化,并探讨其与左心室质量指数(LVMI)和心肌胶原纤维容积分数(CVF)的动态相关关系。方法:大鼠随机分为对照组、假手术组和模型组。腹主动脉缩窄法复制压力负荷增高致大鼠心肌重构的动物模型,模型组进一步分为术后2周、4周、8周和12周组;双抗体夹心ABC-ELISA法,动态检测心肌组织内TNF-α和IL-10表达的变化;改良Mallory氏三色染色检测心肌组织内胶原纤维含量的动态变化。结果:术后4周心肌细胞呈进行性排列紊乱、肌丝断裂,细胞间隙明显增宽,可见大量异常胶原纤维堆积,并在术后12周出现明显的心衰;ELISA检测结果提示,4周、8周和12周组心肌组织TNF-α表达呈时间依赖性升高,与对照组比较,具有显著统计学差异(P<0.01);心肌组织TNF-α表达量与LVMI(r=0.582,P<0.01)和CVF(r=0.932,P<0.01)均呈显著正相关;IL-10在各组心肌组织中的表达无统计学差异,但TNF-α与IL-10比值在术后呈时间依赖性升高,由(1.79±0.19)ng/mL(2周)上升到(2.85±0.24)ng/mL(12周),与对照组(1.74±0.24)ng/mL比较,差异具有统计学意义(P<0.01)。结论:心肌重构的程度呈时间依赖性加剧是心功能恶化的关键因素,TNF-α在心肌组织表达的时间依赖性上调和TNF-α与IL-10比例失调是可能是心肌重构的重要分子机制之一。     

神经干细胞移植治疗帕金森模型鼠的脑内炎症细胞因子变化

目的检测神经干细胞移植后大鼠脑内细胞因子的变化,为营造有利于细胞移植的微环境和神经免疫调节治疗做准备。方法实验检测时间点为移植后1周、2周、4周,在SPF级SD大鼠内随机抽取8只为正常对照组,模型成功稳定的大鼠随机分为生理盐水模型对照组和神经干细胞移植组,每组每个时间点各8只,分别进行脑立体定位注射神经干细胞和生理盐水,到检测时间点时取纹状体制备好样本,用酶联免疫吸附试验双抗体夹心法检测各实验组各时间点纹状体的TNF-α、IL-1β、IFN-γ和IL-4的含量。结果与正常组相比,模型组的TNF-α、IL-1β、IFN-γ、IL-4含量都升高(P<0.05)。与模型组相比,移植组的TNF-α和IL-1β含量降低(P<0.05),IFN-γ和IL-4含量在1周、4周时升高(P<0.05),2周时无差异。与正常组相比,移植组的TNF-α含量在1周、4周时无差异,在2周时稍低(P<0.05),移植组的IL-1β含量在1周时无差异,2周时下降(P<0.05),4周时升高(P<0.05),移植组的IFN-γ和IL-4含量在各时间点均升高(P<0.05)。结论神经干细胞移植入帕金森模型鼠后引起了相关细胞因子的改变,即与模型对照组相比TNF-α、IL-1β水平下降和IFN-γ、IL-4水平升高,说明神经干细胞移植后会使宿主微环境内的部分促炎因子(TNF-α、IL-1β)下降,抗炎因子(IL-4)升高,同时伴随具有神经再生和保护作用的促炎因子(IFN-γ)的升高。     

中小负荷运动对心理应激大鼠血清TNF-α和IL-1β的影响

目的探讨中小负荷运动对心理应激大鼠血清TNF-α和IL-1β含量的影响.方法对大鼠进行为期8周不同负荷的运动训练,并在运动后期施加2周的心理应激,测定大鼠血清中TNF-α和IL-1β含量.结果(1)应激组TNF-α和IL-1 β含量显著低于对照组(P＜0.01).(2)经过8周运动训练后,30min运动组血清IL-1 β含量有上升趋势,但无显著性差异,60min运动组血清IL-1 β含量显著高于对照组(P＜0.05).而TNF-α含量几乎没有变化;(3)30min运动+应激组与60min运动+应激组大鼠血清中TNF-α和IL-1β含量均显著高于应激组,以60min运动组最为明显.结论运动训练可能增加心理应激状态下内源性TNF-α和IL-1β的释放,对抗心理应激的免疫抑制效应.     

高压氧治疗对癫痫大鼠血清白细胞介素1β、白细胞介素2、白细胞介素8、肿瘤坏死因子α水平及海马神经元Bax及Bcl-2表达的影响

目的：探究高压氧治疗对癫痫大鼠血清白细胞介素（IL）1β、IL-2、IL-8、肿瘤坏死因子α（TNF-α）的表 达及海马神经元细胞凋亡基因表达的影响。方法：采用随机数字法将36 只成年健康SD大鼠进行编号,1 ～ 12 号 实验动物为空白对照组,剩余动物接受匹罗卡品建立癫痫模型,根据Racine 评分作为完成标准,随机选取12 只 接受高压氧治疗,利用ELISA 法检测实验动物血清IL-1β、IL-2、IL-8、TNF-α 表达水平,利用免疫印迹和免疫 荧光染色检测实验动物海马神经元细胞凋亡蛋白Bax 和Bcl-2 表达。结果：与空白对照组相比,癫痫模型组大鼠 血清IL-1β、IL-8、TNF-α 表达水平均显著升高,IL-2 表达水平明显降低;经过高压氧治疗后,与癫痫模型组相比, 实验大鼠血清IL-1β、IL-8、TNF-α 表达水平显著降低,IL-2 表达水平明显升高。免疫印迹和免疫荧光染色结果 显示,与空白对照组相比,癫痫模型组促凋亡蛋白Bax 表达显著升高,而抗凋亡蛋白Bcl-2 表达显著下降,经过 高压氧治疗后,Bax 蛋白水平显著下调,而Bcl-2 蛋白水平显著上调。结论：高压氧治疗可减少癫痫大鼠血清IL- 1β、IL-8、TNF-α 的表达,增加IL-2 的表达, Bax 蛋白水平显著下调而Bcl-2 蛋白水平显著上调,因此本研究可作 为高压氧治疗癫痫病作用机制之一。     

Toll样受体4及细胞因子在酒精性肝病发病机理中的作用

目的：探讨肝组织Toll样受体4（TLR4）和白细胞介素1β（IL-1β）、白细胞介素6（IL-6）、白细胞介素10（IL-10）及肿瘤坏死因子α（TNF-α）在酒精性肝病（ALD）发病机理中的作用。方法：应用酒精灌胃建立大鼠酒精性肝病模型,分别于4、8、12和16周末留取血清和肝组织,检测血清IL-1β、IL-6、IL-10及TNF-α含量,应用HE染色、苏丹Ⅳ染色和天狼星红染色观察肝组织病理形态,应用RT-PCR方法观察肝组织Toll样受体4 mRNA表达。结果：随着酒精性肝病病程进展,血清IL-1β、IL-6、IL-10、TNF-α含量逐渐升高（P〈0.05或P〈0.01）,肝组织Toll样受体4 mRNA表达明显增强（P〈0.05或P〈0.01）,IL-10于4、8周时明显升高而于12周后逐渐下降;TLR4相对表达量与IL-1β、IL-6、TNF-α含量呈正相关,与IL-10呈负相关（P〈0.05或P〈0.01）。结论：致炎因子和抗炎因子的表达失衡及Toll样受体4表达增强在酒精性肝病发病过程中发挥着重要作用。     

姜黄素对慢性低灌注大鼠的行为学功能保护作用

目的：探讨姜黄素在慢性低灌注大鼠的神经功能保护作用。方法：制备慢性脑缺血模型(2-VO)模型，术后分别给予姜黄素(实验组)和磷酸盐缓冲液(PBS，对照组)干预。术后8周后行Morris水迷宫评价大鼠的空间学习记忆功能变化。同时从Nissl染色观察大鼠神经细胞的变化；Western blot检测炎症因子IL-1β、TNF-α的表达。结果：实验组大鼠的空间学习记忆能力均较对照组明显改善，差异有统计学意义(P<0.05)；Nissl染色发现实验组大鼠的缺血区神经元细胞与形态相对较为完整，而对照组大鼠神经元形态不完整，仅有散在的尼氏小体；在姜黄素治疗后缺血区脑细胞中IL-1β、TNF-α的含量明显降低(P<0.05)。结论：姜黄素可以显著改善慢性脑缺血大鼠的空间学习记忆能力，可能与其抗炎症反应相关。     

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.