当归多糖对D-半乳糖致小鼠胰腺损伤的保护作用

目的 探讨当归多糖（ASP）对D-半乳糖（D-gal）致小鼠胰腺损伤的保护作用。 方法 雄性C57BL/6 J 小鼠随机分为3组,每组10只。D-gal组: 小鼠皮下注射- gal (120 mg/kg, qd×42 d）; ASP+D-gal组: D-gal注射时间与剂量同D-gal模型组,从模型复制第16天起,腹腔注射ASP(40 mg/kg,qd×27 d）;正常对照组: 小鼠皮下注射等量与等时的生理盐水。各组给药完成后第2天检测相关指标,取外周血检测空腹血糖含量并行口服葡萄糖耐量测定（OGTT）;取胰腺称湿重计算脏器指数;制备石蜡切片,HE染色观察胰腺组织病理结构,图像分析法计数胰岛内有核细胞数和相关面积;制备胰腺组织匀浆,检测丙二醛(MDA)含量和总抗氧化能力（T-AOC）。 结果 从注射D-gal第16天开始,腹腔注射ASP共27 d（ASP+D-gal组）,小鼠胰腺湿重与脏器指数明显降低,组织病理损伤减轻;空腹血糖显著下降;在30 min和120 min的OGTT水平差别不明显;OGTT曲线下面积（AUC）降低;胰岛内有核细胞数减少,单个细胞面积减小;T-AOC活性上升,MDA含量下降。 结论 D-gal可致胰腺结构损伤和功能衰退,ASP能拮抗D-gal从而减轻对胰腺的损伤,其机制可能与减轻氧化损伤有关。     

APP17肽对D-半乳糖性脑老化模型小鼠学习、记忆功能和海马神经元NT-3、NGF表达的影响

目的与方法:用D-半乳糖(D-gal)复制脑老化模型,给模型小鼠皮下注射β-淀粉样肽前体蛋白319-335肽段(APP17p),8周后应用水迷宫实验、神经免疫组化法,观察APP17肽对D-gal脑老化模型小鼠学习、记忆功能及海马神经元中神经营养因子3(NT-3)、神经生长因子(NGF)表达的影响。结果:(1)水迷宫实验D-gal组小鼠游完全程时间及错误反应次数明显高于对照组;APP17肽组小鼠游完全程时间及错误反应次数明显低于对照组和D-gal组。(2)APP17肽组海马神经元NT-3、NGF表达高于C组和D-gal组(P＜0.01)。结论:D-半乳糖性脑老化模型小鼠存在学习、记忆功能障碍,其海马神经元NT-3、NGF表达降低;APP17肽有保护模型小鼠学习、记忆功能的作用,并能促进其海马神经元NT-3、NGF表达的增加。     

还少丹对D-半乳糖致衰小鼠心肌线粒体结构与功能的影响

目的:探讨还少丹对D-半乳糖(D-galactose,D-gal)诱导的衰老模型小鼠心肌线粒体结构与功能的影响.方法:将小鼠随机分为空白对照组、衰老模型组、还少丹低、高剂量组.采用D-gal建立衰老模型,还少丹水煎液灌胃6周.以差速离心法分离小鼠心肌组织线粒体;Comas亮蓝蛋白定量法测定线粒体蛋白含量;分光光度法检测...     

衰老模型小鼠胰腺结构与功能的变化

目的探讨D-半乳糖(D-gal)致衰小鼠胰腺结构与功能变化。方法 2月龄雄性C57BL/6J小鼠随机分为两组,每组10只。衰老组:小鼠皮下注射D-gal(120mg/kg),每天1次,共42 d;对照组:小鼠皮下注射等时与等量生理盐水。衰老模型建立完成第2天,采外周血测定空腹血糖(FBG)与空腹胰岛素(FINS)水平;称小鼠体重(g)与胰腺湿重(mg)计算胰腺脏器指数;石蜡切片,HE染色观察胰腺光学显微镜下形态;制备胰腺冷冻切片,检测衰老相关β-半乳糖苷酶(SA-β-Gal)染色阳性胰腺细胞的相对吸光度(RA);免疫组织化学法观察胰腺组织晚期糖基化终产物(AGEs)的RA;制备胰腺组织匀浆检测超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)和丙二醛(MDA)的含量。结果衰老组小鼠FBG显著升高,FINS水平降低;胰腺湿重和胰腺脏器指数明显升高;胰腺光学显微镜下结构未见显著改变,但胰岛内单个有核细胞所占面积增加;胰腺SA-β-Gal染色阳性细胞数显著增加;AGEs阳性表达区域RA值明显升高;SOD与T-AOC含量显著降低,MDA含量显著升高。结论 D-gal复制衰老小鼠可致其胰腺损伤,其机制与D-gal致胰腺组织细胞的氧化应激损伤有密切关系。     

安五脂素对D-gal致衰老小鼠胸腺的保护作用及其相关机制北大核心CSCD

目的:观察安五脂素对D-半乳糖(D-gal)致衰老小鼠胸腺的保护作用并探讨其相关机制。方法:将ICR小鼠随机分为5组,空白对照组(CON,灌胃羧甲基纤维素钠溶液,皮下注射生理盐水),D-gal模型组(MOD,灌胃羧甲基纤维素钠溶液,皮下注射220 mg/kg D-gal),安五脂素低、中、高剂量组(分别灌胃安五脂素1、2和4 mg/kg,皮下注射220 mg/kg D-gal),1次/d,10 ml/kg,连续造模及给药42 d。计算胸腺指数,观察胸腺组织病理变化,测定血清中IL-2和IFN-γ含量,胸腺组织中SOD活力和MDA含量,应用Western blot法检测胸腺组织中Keap1、Nrf2、HO-1、Caspaes3、Bcl2和Bax等蛋白的表达情况。结果:安五脂素能显著提高胸腺指数并改善受损胸腺结构,提高IL-2和IFN-γ含量,提高胸腺组织中SOD活力,降低MDA含量,上调胸腺组织中Nrf2,HO-1和Bcl2的表达,降低Keap1、Caspase3和Bax的表达水平。结论:安五脂素对D-gal所致的小鼠胸腺损伤具有保护作用,其机制可能与其抗氧化和抗凋亡作用有关。     

D-半乳糖致小鼠胰腺损伤

目的探讨D-半乳糖(D-gal)对小鼠胰腺的损伤及其机制。方法 C57BL/6J小鼠随机分为对照组和D-gal组(D-gal 120 mg/kg,qd×42 d)。注射完成第2天,采外周血测定空腹血糖(FBG)与空腹胰岛素(FINS)水平;称小鼠体质量(g)与胰腺湿重(mg)计算胰腺脏器指数;HE染色观察胰腺组织形态学;透射电镜观察胰腺细胞超微结构;制备冷冻切片,衰老相关β-半乳糖苷酶(SA-β-gal)染色检测胰岛内染色阳性细胞的相对吸光度(RA)值;免疫组织化学法观察胰腺组织晚期糖基化终产物(AGEs)的RA值;制备胰腺组织匀浆检测超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)和丙二醛(MDA)含量。结果 D-gal组小鼠FBG显著升高(P0.05),FINS水平降低;胰腺湿重和胰腺脏器指数明显升高(P0.01);胰腺光镜结构无显著损伤,但胰岛内单个有核细胞所占面积增加(P0.05);胰腺内外分泌部显示细胞超微结构损伤,脂褐素明显沉积;胰腺SA-β-gal染色阳性细胞的RA值增加(P0.05);AGEs阳性表达区域RA值升高(P0.01);SOD与T-AOC含量降低(P0.05),MDA含量升高(P0.01)。结论 D-gal复制衰老小鼠模型可致胰腺损伤,发生机制可能与D-gal致胰腺细胞氧化应激损伤有关。     

蛇菰多糖降低实验性肝损伤大鼠肝脏BDNF和TrkB的表达

目的蛇菰多糖(BPS)对D-半乳糖(D-gal)所致实验性肝损伤大鼠的肝功能及肝组织内BDNF、TrkB蛋白和凋亡相关蛋白表达的影响。方法将大鼠随机分为对照组(control),D-gal组(皮下注射D-半乳糖200 mg/kg),BPS低(D-gal+BPS-L)、中(D-gal+BPS-M)、高(D-gal+BPS-H)剂量组,分别每天灌胃50、100和200 mg/kg BPS,共6周。心脏取血检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平;HE染色法观察肝组织形态;免疫组织化学染色检测BDNF和TrkB的定位;Western blot检测BDNF、TrkB、Bcl-2、caspase-3和Bax蛋白表达;ELISA测定肝组织内丙醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果与对照组相比,D-gal组肝细胞水肿、点状坏死;血清ALT和AST水平升高(P<0.05),SOD活性降低、MDA含量升高(P<0.05);Bax、caspase-3、BDNF、TrkB表达增加(P<0.05),Bcl-2表达降低(P<0.05);与D-gal组相比,BP...     

梅花鹿胎盘提取液对D-半乳糖衰老小鼠免疫功能的影响

梅花鹿胎盘具有补肾壮阳,补虚生精,提高人体运动能力,改善某些生化指标的功效,但对其抗衰老、提高机体免疫力的研究甚少。本实验观察了梅花鹿胎盘提取液的抗衰老作用。实验取体重20±2g健康雄性小鼠30只,将小鼠随机分为三组:正常盐水对照组,模型D—半乳糖(D-gal)组和D-gal加鹿胎盘提取液组。正常对照组和模型组,分别每日颈背皮下注射生理盐水或5%D-gal10.5ml,给药组则在注射D-gal的同时注射梅花鹿胎盘提取液0.2ml,连续用药6周,末次给药后次日断头处死。分别观察:1胸腺组织结构、胸腺重量与体重之比;2小鼠腹腔巨噬细胞吞噬功能测定;3小鼠淋…     

黄芪多糖通过激活脂联素信号通路减轻小鼠溃疡性结肠炎

目的:探讨黄芪多糖治疗小鼠溃疡性结肠炎的效果,并初步探究其作用机制.方法:40只雄性C57BL/6小鼠随机分为空白对照组、模型组、黄芪多糖低剂量组、黄芪多糖中剂量组和黄芪多糖高剂量组,每组8只.除对照组外,其余各组小鼠通过饮用5％葡聚糖硫酸钠盐(DSS)溶液10 d构建溃疡性结肠炎模型.于饮用5％DSS溶液30 min...     

天麻多糖通过影响小鼠免疫系统抑制肿瘤生长

目的研究天麻多糖对小鼠肝癌H22细胞增殖的影响及其对H22荷瘤小鼠肿瘤生长的抑制作用。方法 MTT法检测不同质量浓度的天麻多糖对小鼠肝癌H22细胞体外增殖的影响;健康小鼠和接种H22瘤株造模昆明种小鼠分成7组(n=12):对照组(0.9%NaCl溶液2 ml),模型组(0.9%NaCl溶液2 ml),环磷酰胺(20 mg·kg-1)组,天麻多糖低、中、高剂量(30、60、90 mg·kg-1)组,观察天麻多糖对H22荷瘤小鼠的抑瘤作用。结果天麻多糖对肝癌H22细胞增殖有显著的抑制作用。且在小鼠体内能明显抑制对H22肿瘤瘤体生长,高剂量(90 mg·kg-1)效果明显(P0.05);环磷酰胺和天麻多糖合用可使环磷酰胺对白细胞计数、胸腺指数和脾指数的影响降低。结论天麻多糖能抑制肝癌H22细胞的增殖,与环磷酰胺联用可降低环磷酰胺对免疫系统的伤害。     

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.     

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.     

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.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.