输精管结扎与实验性高血脂对听觉脑干电位及血清过氧化脂质的影响

输精管结扎12月以上日本大耳白兔16只,随机分为输精管结扎基础饲料(V-S)组和输精管结扎胆固醇(V-Ch)组。体重相近的同种雄兔16只,分为对照基础饲料(C-S)和对照胆固醇(C-Ch)组。听觉脑干电位检测结果表明:气导ABR阈值,输精管结扎组(V-S.V-Ch)与各门对照组比较无差异(P<0.05),而高胆固醇饲料组(C-Ch.V-Ch)则显著地高于对照组(P<0.01),并且与TC水平正相关(P<0.01);各组Ⅰ、Ⅲ、Ⅴ波潜伏期无延长,波间期各组比较也无显著差异,(P>0.05)。血清过氧化脂质含量与TC水平正相关(P<0.01)而与血清抗精子抗体滴度无相关(P>0.05)。本实验证明,实验性高血脂使气导ABR阈值及血清过氧化脂质增高,而输精管结扎对其无影响。     

家兔输精管结扎后自身免疫反应与血脂变化的观察

为观察家兔输精管结扎后对精子抗原的自身免疫反应与血脂变化的关系,将输精管结扎后7、9个月日本大耳白雄兔20只,随机分为“结扎·胆固醇组”和“结扎·普食组”,另选月龄相近的同种雄兔20只,分为“对照·胆固醇组”和“对照·普食组”。结果表明,在普食条件下,输精管结扎不引起血脂升高,在高脂饲料条件下,输精管结扎组血脂升高较对照组者为著;实验性高脂血症对结扎兔的体液免疫反应没有抑制作用,面对细胞免疫有较弱的抑制作用。     

植物甾醇酯对大鼠主动脉衰老及相关基因表达的影响

目的:探讨植物甾醇酯延缓大鼠主动脉衰老的作用及其机制。方法:将42只12月龄雌性SD大鼠随机均分为对照组、模型组和植物甾醇酯干预组,分别喂食基础饲料、高脂饲料和高脂加2%植物甾醇酯(W/W)饲料6个月。采用HE染色法和Masson染色法对主动脉横截面石蜡切片进行染色,观察主动脉组织的病理学改变,对血管壁平滑肌细胞和胶原纤维的绝对面积进行图像分析。检测血浆脂质蛋白、晚期糖基化终末产物(AGEs)、丙二醛(MDA)的含量以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性。分别采用real-time PCR和Western blot的方法评估主动脉组织沉默信息调节因子1(SIRT1)和过氧化物酶体增殖物激活受体γ(PPARγ)的mRNA和蛋白表达水平。结果:与模型组相比,植物甾醇酯干预组的血浆总胆固醇和低密度脂蛋白胆固醇水平显著降低,高密度脂蛋白胆固醇的水平相反(P0.05),甘油三酯的水平没有统计学差异;主动脉内膜和中膜的增厚以及平滑肌细胞的迁移均得到改善;主动脉平滑肌细胞和胶原纤维的含量显著下降(P0.05);血浆AGEs的含量显著降低(P0.05);机体的抗氧化功能有所提升,血浆MDA的含量显著减少(P0.05),SOD和CAT活性的差异没有统计学意义;PPARγ的表达下调,SIRT1的表达上调(P0.05)。结论:植物甾醇酯能够延缓大鼠主动脉的衰老。其机制可能与降低机体活性氧的生成有关。植物甾醇酯可能通过激活SIRT1或抑制PPARγ的表达而发挥作用。     

垂体腺苷酸环化酶激活肽对动脉粥样硬化形成过程中脂质过氧化的影响

目的　探讨垂体腺苷酸环化酶激活肽 (PACAP)对家兔实验性动脉粥样硬化 (AS)形成过程中脂质过氧化的影响。方法　 80只雄性新西兰家兔 ,随机分为 3组 :(1)对照组 (C组 ) :喂饲普通颗粒兔饲料 ;(2 )AS模型组 :每只兔每日喂饲含胆固醇 1 5g的颗粒兔饲料 ;(3)PACAP组 (P组 ) :喂饲与AS组同样的饲料 ,另从耳缘静脉注射PACAP。分别于实验的 0、4、8、12周末记录兔体重 ,同时从兔耳中央动脉取空腹血 ,测定丙二醛 (MDA)含量 :并取若干兔的主动脉标本作苏丹Ⅳ染色 ,测量斑块面积。结果　 (1)AS组及P组血清MDA含量均显著高于C组 ;而P组显著低于AS组。 (2 ) 4周末时P组斑块面积显著小于AS组。结论　PACAP具有抗脂质过氧化作用 ,可能与抗AS有关     

活血降脂方对小鼠脂肪肝的防治作用

目的:探讨活血降脂方对小鼠脂肪肝的防治作用及机制。方法:高脂饲料喂养小鼠,分别用不同剂量的活血降脂方(由人参、三七、天麻组成,命名为GST)给小鼠灌胃2周,检测血脂、肝组织甘油三酯(TG)含量,并观察肝指数和肝脏病理变化,筛选出药物的最佳用药剂量。此外,小鼠分为正常对照(NC)组,喂基础饲料;模型组喂高脂饲料。12周后将模型小鼠随机分为高脂(HF)组,正常饮食(ND)组和GST组。除HF组饲高脂饲料外,其余各组饲基础饲料;GST组给予GST灌胃2周,其余各组以同等容积蒸馏水灌胃。检测血清总胆固醇(TC)、TG、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及肝组织TC、TG含量,观察肝指数、肝组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,肝组织病理变化及过氧化物酶体增殖物激活受体α(PPARα)、细胞色素P450 2E1(CYP2E1)的mRNA表达。结果:GST可显著降低血脂、肝脂和MDA水平,增加SOD活性,明显降低肝指数并改善肝组织脂肪变性,增加肝组织PPARαmRNA表达、抑制CYP2E1 mRNA的表达。结论:GST具有有效防治脂肪肝的作用,其机制可能与上调肝组织PPARαmRNA的表达、降低血清和肝组织TG含量、下调CYP2E1 mRNA的表达以及抗脂质过氧化反应有关。     

PPAR-γ激动剂对高脂血症大鼠合并重症急性胰腺炎的作用

<正>目的:探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)激动剂罗格列酮(ROSI)对高脂血症大鼠合并重症急性胰腺炎(SAP)的保护作用及其可能机制。方法:将120只SD大鼠随机分为两个大组:普通饲料组(n=40只)、高脂饲料组(n=80只)。高脂饲料的主要成分为77%基础饲料+20%猪油+3%胆固醇。喂养两周后再随机分组:普通饲料组分为假手术组(SO组)和SAP组;高脂饲料组分为假手术组(HL组)、高脂血症合并SAP组(HAP组)、ROSI预处理组(HR组)、ROSI拮抗组(HRI组),每组各20只。     

Ibrolipim抗猪动脉粥样硬化的作用

目的：探讨合成化合物NO-1886(ibrolipim)调节贵州小香猪脂代谢异常及其抗动脉粥样硬化(AS)的作用机制。 方法： 贵州小香猪15头，按体重随机分为3组。分别喂普通猪饲料(CD)；高脂高蔗糖饲料(HFSD)和高脂高蔗糖饲料加1％ibrolipim。每月末采集血样，测定血脂浓度。第8个月末处死动物，用高效液相色谱(HPLC)分析血浆高密度脂蛋白中胆固醇酯的含量；苏丹Ⅳ染色观察主动脉脂纹的面积；油红O染色观察脂质在肝组织中的沉积。 结果： HFSD组血浆总胆固醇(TC)、甘油三酯(TG)和游离脂肪酸(FFA)浓度均高于对照组，主动脉可见脂纹，内膜增厚，内皮细胞损伤，内膜下有大量泡沫化细胞，肝细胞胞浆内大量脂质沉积；ibrolipim组血浆高密度脂蛋白胆固醇(HDL-C)水平高于对照组（其中胆固醇酯高于对照组,TG和FFA浓度低于对照组），肝细胞油红O染色见少量脂质沉积。 结论： Ibrolipim可能主要是通过降低血浆TG及升高HDL-C发挥其抗AS作用。     

芪参降脂饮对高胆固醇血症大鼠早期动脉粥样硬化的干预作用

目的:观察芪参降脂饮对高胆固醇血症大鼠早期动脉粥样硬化(AS)形成的影响。方法:将24只SD大鼠随机分为对照组,模型组和中药组,分别喂以普通饲料、高脂饲料和高脂饲料+芪参降脂饮;每组各8只。6周后采血,测血清胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白-胆固醇(LDL-C)水平,观察主动脉壁组织形态学变化,检测主动脉血管壁细胞间粘附分子-1(ICAM-1)蛋白表达水平。结果:中药组大鼠血清TC水平明显低于模型组(P<0.01),主动脉内皮损伤明显轻于模型组,中膜平滑肌排列亦较模型组整齐,大鼠主动脉壁ICAM-1蛋白表达量明显低于模型组(P<0.01)。结论:芪参降脂饮能够降低血脂,抑制ICAM-1在血管壁的表达和单核细胞浸润,抑制平滑肌细胞增生,防止早期AS形成。     

不同造模方法对金黄地鼠颈动脉粥样硬化的影响

目的建立改良新型金黄地鼠颈动脉粥样硬化模型,探讨高血脂、高血糖、剪切应力异常对动脉粥样硬化的影响。方法雄性叙利亚金黄地鼠100只,随机分为对照组(N组)、高血脂组(L组)、高血糖组(G组)、高血脂+高血糖组(L+G组)及高血脂+颈动脉结扎组(L+L组),每组20只。其中N组喂食普通饲料; L组喂食高脂饲料; G组一次性腹腔注射链脲佐菌素(STZ,40 mg/kg),普通饲料喂养; L+G组喂养高脂饲料4周后一次性腹腔注射STZ(40 mg/kg); L+L组采用高脂饲料喂养4周后结扎左侧颈内动脉和颈外动脉,保留枕动脉。造模后第10周、第20周每组各取10只金黄地鼠先行下腔静脉置管,抽取血液检测各组血糖及脂质代谢水平;再采用数字乳腺机行双侧颈总动脉血管造影检查,观察双侧颈总动脉血管形态变化;最后处死金黄地鼠,切取主动脉弓及双侧颈总动脉,固定包埋后HE染色观察动脉粥样硬化斑块情况。结果血生化分析表明第10周、第20周,L组、L+G组、L+L组金黄地鼠总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)含量均高于N组和G组(P 0.05),其中L+G组变化最为显著,同时伴有三酰甘油(TG)含量高于其他组(P 0.05); G组、L+G组金黄地鼠血糖含量明显高于N组、L组、L+L组(P 0.05); L+G组胰岛素含量高于其他组(P 0.05),L组与N组胰岛素含量均明显上升,但仅在第10周时2组比较差异有统计学意义(P 0.05)。第20周时,血管造影未见明确血管狭窄或闭塞;仅L+L组双侧颈总动脉血管直径比较,差异有统计学意义(P 0.05),其他组双侧比较差异无统计学意义(P 0.05)。与N组比较,L组、L+G组、G组双侧颈总动脉血管直径较小(P 0.05);而L+L组与其他组比较,左侧颈总动脉血管直径较小,右侧颈总动脉血管直径较大。病理HE染色表明N组双侧颈总动脉未见粥样硬化,L组、G组双侧颈总动脉粥样硬化表现轻微,L+G组、L+L组的金黄地鼠颈总动脉出现明显动脉粥样硬化。结论高血脂联合高血糖或高血脂联合颈动脉结扎均可加速金黄地鼠颈动脉粥样硬化模型的建立。     

吡格列酮对高脂血症大鼠血清一氧化氮、髓过氧化物酶的影响

目的:观察吡格列酮改善血脂与氧化应激、炎症对内皮功能的影响。方法:清洁级SD大鼠26只,随机分为普通饲料组(对照组,n=9)和高脂饲料组(n=17);高脂饲料组喂饲高脂饲料12周后检测空腹血脂,造模成功后,分为模型组(n=8)和吡格列酮组(n=9);后者给予吡格列酮溶液(0.6mg/ml)连续灌胃4周,对照组和模型组给予等量蒸馏水灌胃4周。之后检测各组主动脉病理组织学、血脂、一氧化氮(NO)、髓过氧化物酶(MPO)水平变化。结果:高脂饲料喂养12周后,高脂饲养组甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)较对照组明显升高(P<0.01),提示模型成功。给药4周后,吡格列酮组TG、TC明显下降(P<0.01);血清NO明显升高(P<0.01),血清MPO水平明显下降(P<0.01)。结论:血清NO和MPO可能介导高脂饮食之氧化应激所致血管内皮损伤。吡格列酮可在一定程度上保护血管内皮。     

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.     

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.     

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.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'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.