绝经后骨质疏松症模型体视学测量和机理初探

目的:观测去势术后大鼠骨组织体视学的改变,复制绝经后骨质疏松症的动物模型,初步探讨骨质疏松症的发病机制。方法:将31只3月龄雌性SD大鼠随机分为卵巢切除术组(OVX)和假手术组(sham),术后28d和56d分别处死。测量子宫湿重,骨矿物密度(BMD)和骨组织形态计量参数,分析骨组织微结构的变化。结果:OVX组术后28d和56d大鼠子宫湿重和股骨远端1/3处骨密度均显著少于sham组(P＜0.05);OVX组股骨远端和胫骨近端的干骺端骨小梁面积百分率显著少于sham组(P＜0.01)。结论:卵巢切除术后大鼠股骨远端骨矿物密度和骨组织形态计量学参数稳步下降,胫骨近端骨矿物密度和骨组织形态计量学参数迅速下降而且不稳定;雌激素减少导致的骨质疏松主要发生在长骨的干骺端,骨骺受影响较少;骨组织形态计量参数中骨小梁面积百分比敏感性和稳定性较高。     

去卵巢大鼠骨组织的变化

目的：观察去卵巢对大鼠骨组织的改变，以建立妇女绝经后骨质疏松的动物模型。方法：选用３月龄ＳＤ雌性大鼠１６只，随机分为对照组和去卵巢组。去卵巢组的大鼠的双侧卵巢被切除，对照组做假手术，持续９０天。用骨矿测定仪测量大鼠股骨的骨密度及在半自动图像分析仪观测胫骨近端骨小梁的静、动态指标，并在扫描电镜下观察大鼠股骨松质骨结构的改变。结果：与对照组比较，去卵巢组大鼠股骨远端的骨密度明显降低。胫骨骨小梁的面积减     

去卵巢大鼠骨组织的变化

目的:观察去卵巢对大鼠骨组织的改变,以建立妇女绝经后骨质疏松的动物模型。方法:选用3月龄SD雌性大鼠16只,随机分为对照组和去卵巢组。去卵巢组的大鼠的双侧卵巢被切除,对照组做假手术,持续90天。用骨矿测定仪测量大鼠股骨的骨密度及在半自动图像分析仪观测胫骨近端骨小梁的静、动态指标,并在扫描电镜下观察大鼠股骨松质骨结构的改变。结果:与对照组比较,去卵巢组大鼠股骨远端的骨密度明显降低。胫骨骨小梁的面积减少,骨小梁间隙增加。股骨的骨小梁减少,变细,断裂,连接不紧密,表面常见骨吸收形成的陷窝。结论:用切除卵巢的方法造成雌激素缺乏,导致骨质疏松,是研究因绝经引起原发性骨质疏松的可靠动物模型。     

去卵巢大鼠骨组织的变化

目的:观察去卵巢对大鼠骨组织的改变,以建立妇女绝经后骨质疏松的动物模型。方法:选用3月龄SD雌性大鼠16只,随机分为对照组和去卵巢组。去卵巢组大鼠的双侧卵巢被切除,对照组做假手术,持续90天。用骨矿测定仪测量大鼠股骨的骨密度及在半自动图像分析仪观测胫骨近端骨小梁的静、动态指标,并在扫描电镜下观察大鼠股骨松质骨结构的改变。结果:与对照正常组比较,去卵巢组大鼠股骨的远端的骨密度降低(P<0.05)。胫骨骨小梁的面积减少,骨小梁间隙增大。股骨的骨小梁变少,变细,断裂,连接不紧密,表面常见骨吸收形成的陷窝。结论:用切除卵巢的方法造成雌激素缺乏,导致骨质疏松,作为研究因绝经引起的原发性骨质疏松的可靠动物模型。     

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。     

中等强度跑台运动对去卵巢大鼠股骨头骨松质结构的影响

目的:观察中等强度跑台运动对去卵巢大鼠股骨头骨松质结构的影响,探讨运动对绝经期妇女骨质疏松的预防作用。方法:SD大鼠随机分为假手术组、去卵巢手术组、雌激素对照组和运动组。假手术组进行模拟手术不切除卵巢,其余各组行双侧卵巢切除术。手术2周后开始为期8周的干预治疗。雌激素对照组用尼尔雌醇治疗,运动组按要求进行运动。治疗结束后取股骨头骨松质进行树脂包埋及体视显微观察并进行骨组织形态计量学分析。结果:运动组的骨小梁面积、骨小梁厚度、骨小梁数量明显高于去卵巢手术组,骨小梁分离度、骨小梁游离末端数显著低于去卵巢手术组。结论:中等强度运动可以抑制去卵巢导致的大鼠股骨头骨松质骨量的丢失,确保其骨结构的维持,保证其正常的骨强度。     

力学加载大小对去势大鼠骨组织形态计量学影响的实验研究

观察不同强度的力学加载对去势大鼠骨组织形态计量学参数的影响。取35只9月龄雌性SD大鼠,随机分为5组,即假手术组,去势对照组,去势加载1N组、去势加载2N组、去势加载4N组。加载组大鼠加载4周后处死,取胫骨上端松质骨进行树脂包埋,不脱钙切片。观察骨组织形态计量学参数。结果表明：加载组大鼠的骨小梁面积百分率、骨小梁厚度、骨小梁数量明显高于去势对照组,骨小梁分离度明显低于去势对照组。动态参数显示,去势组大鼠的骨转换明显高于去势加载组和假手术组。随着载荷的增加,大鼠骨形态计量学的各个参数和骨的微观结构均有所改善。说明力学加载对去势大鼠骨组织微观结构有较大的改善,能够有效地减少骨量的丢失,减缓由于去势引起的骨质疏松的进程。     

去卵巢骨质疏松大鼠成骨细胞G_1期调节蛋白的改变

背景:G1期调节蛋白对调控增殖细胞的增殖周期具有重要作用,目前关于成骨细胞G1期调节蛋白的研究甚少,绝经后骨质疏松与成骨细胞G1期调节蛋白的关系更未被阐明。目的:观察去卵巢大鼠骨质疏松发病过程中成骨细胞G1期调节蛋白的改变,探讨绝经后骨质疏松症的发病机制。方法:100只6月龄SD雌性大鼠,随机分成假手术组和模型组各50只,模型组进行双侧卵巢结扎切除术,假手术组除未行卵巢结扎切除外,其余步骤与手术组相同。所有大鼠于术后4,8,12,18,24周分批取材,每批每组各处死10只,取大鼠腰椎。运用免疫组织化学方法检测骨组织中成骨细胞G1期调节蛋白CyclinD1、CDK4、p21蛋白表达。结果与结论:CyclinD1、CDK4蛋白阳性表达主要定位于骨小梁表面的成骨细胞。假手术组有CyclinD1、CDK4蛋白阳性表达,模型组表达强于假手术组。p21蛋白阳性表达部位与CyclinD1相似,假手术组和模型组均有明显阳性表达,但模型组的表达维持在较高水平,在各时期均明显高于同期假手术组(P0.01)。结果证实,去卵巢骨质疏松模型大鼠发病过程中,成骨细胞CyclinD1、CDK4、p21蛋白出现明显高表达。提示成骨细胞增殖加快,同时成骨细胞周期受阻滞亦增多,成骨细胞数量相对不足,骨形成低于骨吸收,导致骨质疏松的发生。     

尼尔雌醇对去卵巢大鼠胫骨骨重建的影响

目的　探讨尼尔雌醇防治绝经后骨质疏松 (PMO)的作用机制。方法　雌性Wistar大鼠30只 ,随机分成假手术组、去卵巢组和尼尔雌醇治疗 (N)组。假手术组进行假手术 ,其余 2组切除卵巢制备PMO模型 ,N组使用尼尔雌醇治疗 3个月。各组动物处死后 ,取一侧胫骨提取总RNA ,逆转录 聚合酶链反应 (RT PCR)检测白细胞介素 (IL 6 )mRNA表达情况。另一侧用骨形态计量学方法研究去卵巢大鼠胫骨干骺端对尼尔雌醇的治疗反应 ,包括静力学参数 :(1)骨小梁体积 (TBV)占全部骨组织体积 (TTV)的百分比 (TBV/TTV) ;(2 )骨小梁表面与其体积之比 (S/V) ;(3)TBV占海绵骨 (SBV)体积的百分比 (TBV/SBV) ;(4 )平均骨小梁板厚度 (MTPT) ;(5 )平均骨小梁板密度 (MTPD) ;(6 )平均骨小梁板间隙 (MTPS) ;(7)平均骨皮质厚度 (MCW)。动力学参数 :(1)骨小梁类骨质表面占骨小梁表面的百分比 (TOS) ;(2 )平均类骨质宽度 (MOSW) ;(3)四环素单标记线占骨小梁表面的百分比 [Sfract(s) ];(4 )四环素双标记线占骨小梁表面的百分比 [Sfract(d) ];(5 )四环素单标记线的 1/ 2和双标记线之和占骨小梁表面的百分比 [Sfract(s/ 2 d) ];(6 )四环素双标记线间的平均距离 (DDL) ;(7)矿化沉积率 (MiAR) ;(8)矿化延迟时间 (MLT) ;(9)组织水平的骨形成率 (Svf) ;     

Micro CT定量研究去卵巢山羊胫骨平台松质骨微结构特点

背景：骨质疏松时胫骨平台松质骨微结构发生显著变化,Micro CT是一种能够全面、立体、无创测量骨微结构、评估骨质量及预测骨强度的新兴技术,近年来在骨质疏松研究领域得到日益广泛的应用。 目的：应用Micro CT技术定量研究去卵巢山羊胫骨平台松质骨的微结构特点。 方法：将12只2.5岁健康雌性山羊随机分为去卵巢组和假手术组,去卵巢组行卵巢切除,假手术组切除等量腹腔脂肪组织,每组各6只。两组实验动物分别在术后2,4年处死,分离并截取左侧胫骨平台,行Micro CT扫描,分别测量胫骨平台骨骺松质骨和干骺端松质骨微结构参数。 结果与结论：术后2和4年,与假手术组相比,去卵巢组胫骨平台骨骺和干骺松质骨微观结构参数-骨体积分数、骨小梁数量和骨小梁厚度均降低(P < 0.05),骨小梁分离度均升高(P < 0.05),基本呈时间依赖性变化。仅在术后4年,去卵巢组骨骺松质骨微观结构参数骨小梁厚度与假手术组相比差异无显著性意义(P > 0.05),其骨小梁分离度、骨小梁厚度与去卵巢组术后2年相比差异无显著性意义(P > 0.05)。无论术后2或4年,与假手术组相比,去卵巢组干骺端松质骨微结构参数的改变均比骨骺松质骨明显。结果证实,山羊胫骨平台骨骺松质骨微结构参数与干骺端松质骨具有一定的差异;骨质疏松时山羊胫骨平台松质骨微结构改变呈现出区域性特点,干骺端松质骨较骨骺松质骨微结构退变更为显著。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

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.