去势大鼠5种骨转换生化指标的动态变化

目的： 对去势大鼠骨质疏松动物模型形成过程中5种骨转换指标的变化及其相关性进行研究。方法: 将3月龄SD雌性大鼠分为3组：切除卵巢组(OVX)，假手术组(sham)和对照组(control)，术前和术后分别于1、1.5、2、2.5、3和4月检测血清骨钙素(OC)、碱性磷酸酶(ALP)、 骨碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRAP)和羟脯氨酸(HYP)水平，并作大鼠胫骨病理切片检查。结果: OVX组血清OC、ALP、BALP、TRAP和HYP水平均明显高于sham组，其变化顺序依次为：TRAP/HYP→OC→ALP/BALP；5种指标之间呈显著正相关；术后3月OVX组大鼠胫骨小梁结构有病理改变。结论: 去势大鼠属于高转换型骨质疏松；在模型形成过程中，骨吸收指标的变化早于骨形成指标的改变；骨转换指标是反映绝经后早期骨量丢失的灵敏指标。     

六月龄大鼠去卵巢后建立骨质疏松症模型的可行性

背景：目前关于鼠龄对去势雌性大鼠建立骨质疏松模型影响的报道较少。 目的：验证6月龄大鼠去卵巢对构建骨质疏松症模型的可行性。 方法：6月龄雌性大鼠48只,分为2组,去卵巢组摘除双侧卵巢建立大鼠骨质疏松模型,假手术组不摘除卵巢,切除卵巢周围少量脂肪组织。建模后1,2,3个月测定大鼠体质量、子宫湿质量、碱性磷酸酶、抗酒石酸酸性磷酸酶、骨矿密度和骨矿含量等指标变化。 结果与结论：建模后1,2,3个月,去卵巢组比假手术组大鼠体质量明显增加(P < 0.05),子宫湿质量较假手术组量明显下降(P < 0.05)。建模后1个月,去卵巢组大鼠血清碱性磷酸酶指标显著高于假手术组(P < 0.05);建模后3个月,去卵巢组抗酒石酸酸性磷酸酶指标显著高于假手术组(P < 0.05);碱性磷酸酶指标和抗酒石酸酸性磷酸酶指标随大鼠月龄增加有轻度增高趋势。建模后2,3个月去卵巢组骨矿密度显著低于假手术组(P < 0.05)。表明6月龄大鼠去卵巢可成功建立骨质疏松症模型。     

咀嚼力增强对骨质疏松大鼠颌骨骨丢失的保护作用及机制

为研究咀嚼力增强对骨质疏松大鼠颌骨骨丢失的保护作用及机制,选取30只雌性SD大鼠进行实验,行摘除卵巢术建立骨质疏松动物模型,喂食高硬度饲料建立咀嚼力增强动物模型,检测血清雌二醇(E2)、骨钙素(BGP)、碱性磷酸酶(ALP)、牙槽骨骨形态计量学指标、TGF-β与OPG、RANKL基因等指标.结果显示,与模型组相比,实验...     

黄精多糖对骨质疏松性骨折大鼠骨代谢因子的影响

背景：骨质疏松性骨折主要原因是雌激素减少所形成的高转换型骨质疏松,采用雌激素虽能够有效地治疗,但长期雌激素替代治疗会引发诸多疾病。 目的：观察黄精多糖对骨质疏松性骨折大鼠骨代谢因子的影响。 方法：6月龄雌性SD大鼠,随机分为对照组(n=8)和骨质疏松性骨折组(n=36)。骨质疏松性骨折组行卵巢切除后建立骨质疏松性骨折动物模型,再以0.066 mg/kg雌激素,400,200,100 mg/kg 黄精多糖进行灌胃,2 d/次,连续35 d。采用Elisa方法测量骨钙素、抗酒石酸酸性磷酸酶的表达。 结果与结论：骨质疏松性骨折大鼠的骨钙素、抗酒石酸酸性磷酸酶的阳性表达活性升高,给予黄精多糖干预治疗后,高剂量的黄精多糖使骨钙素、抗酒石酸酸性磷酸酶的阳性表达活性下降,而在中、低剂量组干预效果不显著。说明高剂量黄精多糖对骨质疏松性骨折大鼠具有降低骨钙素、抗酒石酸酸性磷酸酶的阳性表达活性的作用,促进骨折愈合的作用。     

雌激素受体调节剂联合游泳运动干预去卵巢大鼠骨生化指标的变化

背景:研究发现运动和雌激素联合作用对去卵巢大鼠松质骨骨量的丢失有预防作用,但有关运动与选择性雌激素受体调节剂联合作用对骨代谢的影响方面的研究较少。目的:通过对去卵巢大鼠血液生化指标的比较,探讨游泳运动与选择性雌激素受体调节剂联合作用对去卵巢大鼠骨代谢的影响。方法:将50只雌性SD大鼠随机分为5组:假手术组仅手术不切除卵巢,其余各组去卵巢造模,运动组、药物组及运动+药物组分别在去卵巢的基础上进行游泳训练和(或)灌胃选择性雌激素受体调节剂雷洛昔芬。8周后,比较各组大鼠血液生化指标的变化。结果与结论:卵巢摘除的早期对大鼠进行运动干预可抑制大鼠体质量的快速增加。与模型组比较,运动组、药物组、运动+药物组大鼠血磷及碱性磷酸酶水平明显升高(P0.05或P0.01),血清抗酒石酸酸性磷酸酶水平显著降低(P0.05),均以运动+药物组效果最明显,但各组间血钙水平差异无显著性意义(P0.05)。说明游泳运动和(或)选择性雌激素受体调节剂均可在一定程度上改善骨代谢的血液生化指标,延缓骨丢失,抑制高转换型骨代谢率,以选择性雌激素受体调节剂和运动联合作用效果最佳。     

两种肾虚证型去势模型大鼠骨小梁微观结构及骨代谢的差异

背景:目前去势大鼠是成熟可靠的骨质疏松症动物模型,对肾阳虚证、肾阴虚证大鼠模型的建立与相关观察指标也已有比较详细的研究,但对肾阳虚证、肾阴虚证骨质疏松的"病证结合"大鼠模型研究还有待完善。交感-副交感神经功能测定是判断阴虚、阳虚证型的一个特异性指标,但用来分析两种肾虚证型骨骼系统相关指标方面仍存在不足,"病证结合"需要更多的实验依据和观察指标。目的:比较分析肾阳虚证和肾阴虚证骨质疏松大鼠骨小梁微观结构参数及血清中骨代谢指标的差异。方法:手术摘除20只SD雌性大鼠双侧卵巢建立去势骨质疏松模型,10周后随机分为肾阳虚组、肾阴虚组,每组10只。肾阳虚组去势大鼠臀部肌肉注射氢化可的松注射液,肾阴虚组去势大鼠灌胃甲状腺片混悬药液,均1次/d,连续14 d,造模成功后采用Micro-CT扫描获取大鼠左侧股骨感兴趣区域骨微结构参数,ELISA法检测大鼠血清中骨形成及骨吸收相关指标。结果与结论:(1)成功建立两种肾虚证型去势骨质疏松大鼠病证结合模型;(2)与肾阳虚组大鼠相比,肾阴虚组大鼠骨小梁骨密度及骨体积分数明显升高,骨小梁数量增加,骨小梁厚度减小,血清各项骨形成、骨吸收指标明显升高,提示肾阴虚组大...     

金雀异黄酮对去卵巢大鼠骨质疏松性骨折愈合的实验研究

目的研究金雀异黄酮对去势大鼠发生骨质疏松性骨折愈合的影响。方法成年SD大鼠卵巢摘除后3个月开始制作左侧股骨中段闭合骨折内固定手术模型,并分为骨折组和骨折用药组,每组各20只骨折用药组注射金雀异黄酮,分别于大鼠折骨后15和30dX射线摄片、检测血清骨碱性磷酸酶(B鄄ALP)、I型前胶原羧基端肽(PICP)、骨钙素(BGP)等骨形成生化指标,并与骨折组比较。结果骨折用药组骨痂形成量多,骨折线模糊或消失,B鄄ALP、PICP和BGP水平显著下降(P<0.01)。结论金雀异黄酮可调节骨代谢,促进骨形成,加快大鼠骨折愈合的作用。     

阿仑膦酸钠与雷洛昔芬对牙槽骨吸收的影响

背景：研究证明阿仑膦酸钠与雷洛昔芬对骨质疏松有抑制作用。 目的：建立实验性大鼠骨质疏松及牙槽骨吸收模型,评价阿仑膦酸钠与雷洛昔芬对骨吸收的防治作用。 方法：56只雌性SD大鼠建立骨质疏松及牙槽骨吸收的动物模型,实验动物分组：①去势+结扎组和单纯结扎组又分别分为3个亚组：阿仑膦酸钠组、雷洛昔芬组和非用药组。②单纯去势非用药组。③假手术组做空白对照。建模手术后第5日开始灌胃给药,1次/d,治疗3个月。用血生化指标、骨密度测量及组织形态学方法进行药效评价。 结果与结论：阿仑膦酸钠治疗组较雷洛昔芬组有更强的降低去势组碱性磷酸酶和血钙的作用;提高去势组骨密度。结果证实阿仑膦酸钠与雷洛昔芬均能减少骨质丢失,从而可以防止骨质疏松及病理性牙槽骨骨吸收,且阿仑膦酸钠作用较好。     

雌二醇对铅中毒模型大鼠骨组织及骨代谢指标不能产生影响

背景：关于铅中毒能否引起骨质疏松症及雌激素对其治疗是否有效尚无共识。 目的：观察雌二醇对去卵巢大鼠和铅中毒大鼠所致骨质疏松症的治疗效果。 方法：雌性大白鼠100只等分成正常对照组、去卵巢模型组、染铅模型组、雌二醇+去卵巢组和雌二醇+染铅模型组。建模后1周雌二醇+去卵巢组和雌二醇+染铅模型组皮下注射雌二醇(100 μg/kg),2次/1周,连续12周。 结果与结论：在去卵巢模型组和铅中毒组中骨钙、骨磷、血钙及血磷均出现降低(P < 0.01),血碱性磷酸酶升高(P < 0.01),骨组织形态呈现骨质疏松的病理改变。雌二醇+去卵巢组的骨代谢生化指标血钙、磷、和碱性磷酸酶和骨组织形态均恢复正常,而雌二醇+铅中毒组的骨代谢生化指标和骨组织形态呈现骨质疏松未出现明显改善迹象。铅中毒组和雌二醇+铅中毒组的骨铅和血铅明显高于正常对照组(P < 0.01)。说明铅中毒可引起骨质疏松的病理改变,雌二醇对去卵巢大鼠的骨质疏松症有良好治疗效果,而对铅中毒所致的骨质疏松症无明显疗效。     

骨髓间充质干细胞移植可提高骨质疏松大鼠骨代谢水平北大核心

背景:研究证实骨髓间充质干细胞具有增加骨保护素水平、促进骨代谢的作用。目的:探讨骨髓间充质干细胞对骨质疏松大鼠骨代谢的影响。方法:实验所用健康SD大鼠42只,随机分为假手术组、骨质疏松组、干细胞移植组,每组14只,后2组采用去卵巢法制备大鼠骨质疏松症模型,造模成功后干细胞移植组经尾静脉移植骨髓间充质干细胞,移植28 d后采用ELISA法检测各组大鼠血清骨保护素、碱性磷酸酶、抗酒石酸酸性磷酸酶、骨钙素、胰岛素样生长因子1水平;Western blot检测各组大鼠骨组织中FoxO1的表达;AG-IX生物力学万能试验机检测股骨最大载荷和断开裂载荷;苏木精-伊红染色观察大鼠骨形态学改变。结果与结论:①骨质疏松组骨保护素、碱性磷酸酶、胰岛素样生长因子1水平低于假手术组(P<0.05),抗酒石酸酸性磷酸酶、骨钙素水平高于假手术组(P<0.05);干细胞移植组骨保护素、碱性磷酸酶、胰岛素样生长因子1水平高于骨质疏松组(P<0.05),抗酒石酸酸性磷酸酶、骨钙素的表达水平低于骨质疏松组(P<0.05);②骨质疏松组最大载荷、断裂载荷值均低于假手术组(P<0.05);干细胞移植组最大载荷、断裂载荷值高于骨质疏松组(P<0.05);③干细胞移植组骨小梁明显增粗,排列较为有序,局部间隙较均匀,较骨质疏松组明显改善;④骨质疏松组大鼠骨髓组织中FoxO1蛋白表达水平低于假手术组(P<0.05);干细胞移植组大鼠骨髓组织中FoxO1蛋白表达水平高于骨质疏松组(P<0.05);⑤结果表明,骨髓间充质干细胞移植可提高骨质疏松大鼠骨代谢水平,其作用机制与促进骨保护素、碱性磷酸酶、FoxO1的表达有关。     

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.