D-半乳糖诱导衰老高黏滞血症大鼠模型初探

目的探讨研制简便易行的衰老高黏滞血症(HVS)实验动物模型.方法将青年大鼠分为青年对照组、D-半乳糖致亚急性衰老模型1组、2组.分别在腹部皮下注射0.9%生理盐水、D-半乳糖于10周、6周、10周后以青年组大鼠为对照,观察血液流变性、血小板聚集、抗凝血酶Ⅲ(ATⅢ)活性,肝肾组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量等指标并做主动脉组织病理学检测.结果青年对照组的血浆黏度和SOD呈负相关、衰老模型两组的血浆黏度和SOD呈负相关;与青年组比较,衰老模型1、2组血液流变学的多项指标、血小板最大聚集率、肝肾组织MDA含量等明显增高,AT-Ⅲ活性及肝肾组织SOD活性明显降低,主动脉壁内膜增厚.结论D-半乳糖诱导的衰老大鼠模型具有与老年鼠相似的血液流变学的改变,可用作为衰老高黏滞血症(HVS)实验动物模型.     

葛根黄酮对亚急性衰老模型小鼠抗氧化作用的研究

目的：考察葛根黄酮对衰老模型小鼠抗氧化能力的影响。方法：用D-半乳糖制备衰老模型小鼠,分为正常对照组、模型组、阳性对照组、高、低剂量组,检测各组小鼠血清丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）水平变化。结果：葛根黄酮能显著降低衰老小鼠血清MDA水平,同时可提高SOD和GSH-PX活力水平。结论：葛根黄酮对亚急性衰老模型小鼠具有抗氧化作用。     

三七皂甙Rg1对D-半乳糖衰老鼠脑星型胶质细胞保护作用的研究

为了探讨三七皂甙Rg1对D-半乳糖所致衰老模型鼠氧化损伤及星型胶质细胞衰老的保护作用。将小鼠随机分为3组:衰老模型组、正常对照组和实验组。采用跳台法测定小鼠的学习记忆行为,采用生化方法分光光度法检测鼠脑海马区SOD和MDA水平,免疫组化方法观察鼠海马区胶质细胞酸性蛋白(GFAP)的表达。结果显示:三七皂甙Rg1能使D-半乳糖衰老模型鼠海马区抗氧化物酶SOD活性升高,MDA含量明显降低,GFAP的表达明显减少。结果提示:三七皂苷Rg1可能通过减轻D-半乳糖所致氧化损伤程度延缓脑神经胶质细胞的衰老,从而改善模型鼠的学习记忆能力。     

白藜芦醇对D-半乳糖诱导的亚急性衰老小鼠海马神经元的保护作用

目的 探讨白藜芦醇对亚急性衰老小鼠海马神经细胞的保护作用.方法 D-半乳糖颈背部皮下注射制备亚急性衰老小鼠模型,设正常对照组、对照组、高低剂量处理组和阳性对照组.第3周始,处理组分别给予白藜芦醇15、45mg/kg(低、高剂量)灌胃,对照组给予生理盐水或DMSO溶液灌胃.8周后,检测小鼠血清、脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量.制作石蜡切片,尼氏染色观察小鼠海马CA1区形态结构,免疫组化检测P53蛋白表达,TUNEL法检测细胞凋亡.结果 各组小鼠海马组织形态结构无明显变化;与对照组相比,白藜芦醇45 mg/kg体重组小鼠血清和脑组织中SOD活性明显升高,MDA含量明显下降;白藜芦醇45 mg/kg体重组小鼠海马CA1区P53蛋白表达阳性细胞较对照组小鼠减少,但各组均无明显的凋亡细胞.结论 白藜芦醇能增强亚急性衰老小鼠的抗氧化功能,降低亚急性衰老小鼠海马CA1区神经元P53蛋白的表达.     

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。     

普洱茶膏抗小鼠衰老的保健作用

目的:观察普洱茶膏对D-半乳糖致衰老模型小鼠抗衰老的保健作用。方法:昆明种清洁级小鼠30只随机分成3组:正常对照组、D-半乳糖模型组及普洱茶膏组;D-半乳糖模型组及普洱茶膏组每天给予皮下注射5%D-半乳糖0.25ml·10g-1,持续6w。第2w后分别给予生理盐水及普洱茶膏(60mg·ml-1)0.5ml灌胃,连续干预4w后,测定血清、肝组织中SOD和MDA水平,并计算肾脏指数、脾脏指数和肝脏指数。结果:与对照组相比,模型组血清MDA含量明显升高(P0.05),而血清SOD活性以及肾脏、脾脏和肝脏指数均显著降低(P0.05);与模型组相比,普洱茶膏组可明显降低MDA含量(P0.05),并明显升高血清、肝组织中SOD的含量(P0.05)以及肾脏、脾脏和肝脏指数(P0.05)。结论:普洱茶膏具有良好的抗小鼠衰老的保健作用。     

白藜芦醇对抗D-半乳糖诱导的心肌细胞衰老及其机制

 目的：探讨白藜芦醇对D-半乳糖诱导的心肌细胞衰老的影响及其可能机制。方法：用不同浓度D-半乳糖（0、0.1、1、10和100 g/L）作用不同时间（0、12、24、48和72 h）诱导原代心肌细胞衰老,通过β-半乳糖苷酶染色法鉴定细胞衰老,MTT法检测细胞活力,FDG法半定量检测β-半乳糖苷酶含量,构建体外心肌细胞衰老模型。根据FDG的结果来评估不同浓度白藜芦醇（2、10、50和250 μmol/L）处理对衰老心肌细胞的影响,通过检测超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量及微管相关蛋白1轻链3（LC3）的变化来探讨白藜芦醇处理效应产生的可能机制。结果：与对照组相比,衰老组（10 g/L D-半乳糖处理48 h）β-半乳糖苷酶染色阳性率明显增加,β-半乳糖苷酶含量明显增加;SOD活性下降,MDA含量增加;LC3Ⅱ/LC3Ⅰ水平下调;细胞活力无明显变化。与衰老组相比,白藜芦醇处理组（10 μmol/L及 50 μmol/L）β-半乳糖苷酶含量明显降低;SOD活性升高,MDA含量明显降低;LC3Ⅱ/LC3Ⅰ水平上调。结论：D-半乳糖诱导的心肌细胞衰老伴随着氧化应激的增强及自噬水平的下调;白藜芦醇能减轻D-半乳糖诱导的心肌细胞衰老的程度,其保护效应产生的机制可能与白藜芦醇抗氧化应激效应及上调自噬水平相关。     

花生红衣水提物对D-半乳糖衰老小鼠学习记忆能力的影响

目的观察花生红衣水提物对D-半乳糖衰老模型小鼠学习记忆能力的影响。方法 60只雄性昆明小鼠被随机分为空白对照组、衰老模型组、吡拉西坦阳性对照组、花生红衣水提物高、中、低(650.0、325.0、162.5 mg/kg)剂量组。空白对照组颈背部皮下注射0.5 mL生理盐水,其余5组均注射等体积2.5%的D-半乳糖,qd,连续42 d复制小鼠亚急性衰老模型。给药各组在造模同时分别灌胃给予相应药物,42d后通过跳台实验和水迷宫实验检测小鼠学习记忆能力;行为学检测结束后处死小鼠,计算脑、脾脏指数;ELISA法检测小鼠脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果与空白对照组小鼠比较,模型组小鼠体质量增加量明显降低,脑、脾指数显著降低;在跳台实验中潜伏期明显缩短,错误次数增多;在水迷宫实验中潜伏期明显延长,错误次数明显增多;脑组织内SOD活性下降,MDA含量增加。与模型组相比,吡拉西坦组和花生红衣各剂量组小鼠体质量增加量升高,脑、脾指数显著性增加,学习记忆能力提高,还可不同程度提高脑组织SOD活性,降低MDA含量。结论花生红衣水提物可改善D-半乳糖致衰老小鼠的学习记忆能力,作用机制可能与提高机体抗氧化能力和免疫活性有关。     

当归多糖对衰老模型大鼠脾脏结构与功能的影响

目的 探讨当归多糖（ASP）对衰老模型大鼠脾脏结构与功能影响及其机制。 方法 SD大鼠随机分为正常对照组,ASP对照组,衰老模型组,ASP衰老模型组,每组10只。衰老模型组皮下注射D-半乳糖（120mg/kg）qd×42d;ASP衰老模型组注射D-半乳糖的剂量与时间同衰老模型组,第15天起腹腔注射ASP (100 mg/kg) qd×28d;正常对照组皮下注射等量生理盐水qd×42d;ASP对照组注射等量生理盐水qd×14d,第15天起腹腔注射ASP（同ASP衰老模型组)。药物注射完成后第2天,取脾脏测定脾指数,石蜡切片观察脾脏显微形态学;衰老β-半乳糖苷酶（SA-β-Gal）染色观察脾细胞百分率,CCK8测定脾细胞对刀豆蛋白A刺激的增殖能力;流式细胞术检测脾细胞周期与活性氧簇（ROS）含量; ELISA检测脾细胞分泌TNF-α、GM-CSF能力与丙二醛（MDA）、超氧化物歧化酶(SOD)含量;Western blotting 检测衰老相关蛋白P53、P21、RB蛋白表达。 结果 与正常对照组比较,D-半乳糖致衰老模型组大鼠脾指数,脾脏白髓面积比例,脾细胞对刀豆蛋白A刺激的增殖能力,S期比例及TNF-α、GM-CSF的分泌能力,SOD活性明显降低;脾细胞的SA-β-Gal阳性率,G₁期与G₂/M期细胞比例,ROS、MDA含量,P53、P21、RB蛋白表达显著增高。与衰老模型组比较,ASP使D-半乳糖致衰老模型大鼠脾指数,脾脏白髓面积比例,脾细胞对刀豆蛋白A刺激的增殖能力,S期比例与TNF-α、GM-CSF的分泌能力,SOD活性明显提高;脾细胞SA-β-Gal阳性率,G₁期及G₂/M期细胞比例,ROS、MDA含量,P53、P21、RB蛋白表达有显著抑制作用。
结论 D-半乳糖复制的衰老模型大鼠脾脏结构与功能损伤明显,当归多糖对其致衰损伤有明确的保护作用。     

硫化氢对老年小鼠主动脉内皮衰老的影响北大核心CSCD

目的:探讨外源性硫化氢对老年小鼠主动脉内皮衰老的影响及可能机制。方法:8只3月龄雌性C57BL/6小鼠为对照组,16只22月龄雌性老年小鼠随机分为模型组和实验组,分别腹腔注射NaHS或生理盐水处理6周,检测相应指标,验证硫化氢对老年小鼠炎症、氧化应激及主动脉内皮衰老的作用。结果:与对照组相比,模型组小鼠体内细胞黏附分子-1(ICAM-1)和丙二醛(MDA)表达显著增加,超氧化物歧化酶1(SOD1)、内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)表达明显减少,衰老相关标志物纤溶酶原激活物抑制剂-1(PAI-1)表达和衰老相关β-半乳糖苷酶(SA-β-Gal)染色比例明显升高。给予NaHS处理后,前述指标均得到一定程度逆转。结论:硫化氢可能通过抑制老年小鼠体内炎症反应和氧化应激改善主动脉内皮衰老。     

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.