钙敏感受体在黄芪注射液防治心肌损伤中的作用

目的研究黄芪注射液对心肌损伤大鼠钙敏感受体表达的影响及黄芪注射液可能的心肌保护作用机制。方法 40只大鼠随机分为4组:空白组、心肌损伤组、黄芪注射液组(20 mL/kg)、黄芪注射液(20 mL/kg)+钙敏感受体激动剂Cinacalcet(3.0 mg/kg)组。腹腔内注射5 mg/kg异丙肾上腺素,制备大鼠心肌损伤模型。Western blot方法检测各组大鼠心肌组织中钙敏感受体的表达以及Bax、Bcl-2、Caspase-9、Caspase-3等凋亡相关蛋白的表达;TUNEL染色法评价各组大鼠心肌细胞的凋亡;酶联免疫吸附法测定各组大鼠血清炎症因子TNF-α、IL-1β、NF-κB的水平。结果黄芪注射液显著抑制了心肌损伤组大鼠钙敏感受体的表达(P0.01),促进了Bcl-2的表达(P0.01),降低了Bax、Caspase-9和Caspase-3的表达(P0.01),降低了血清TNF-α、IL-1β和NF-κB的水平(P0.01);钙敏感受体激动剂Cinacalcet可以部分消除黄芪注射液对心肌损伤组大鼠的心肌保护作用。结论黄芪注射液对心肌损伤组大鼠的心肌保护作用可能与抑制钙敏感受体的表达、减少炎症反应、降低心肌细胞凋亡有关。     

牛磺酸对大鼠心脏模拟缺血再灌注损伤的保护作用

在离体大鼠心脏模拟缺血再灌注(I/R)损伤的模型上观察了牛磺酸的心肌保护作用。实验结果发现预先给大鼠牛磺酸灌胃(300mg/kg)三日或再灌注同时给药(20mmol/L),对心肌均有保护作用,明显减少心肌细胞内的Mb、LDH的漏出,降低心肌MDA的生成,减轻细胞内钙的聚集,促进心肌ATP含量的恢复。在本实验条件下预防应用牛磺酸较再灌注的同时应用更为有效,表现为更大程度地减少LDH漏出,抑制心肌MDA生成和钙聚集。结果证明牛磺酸具有心肌保护作用,对于防治心肌I/R损伤可能具有临床应用价值。     

异丙肾上腺素下调NADPH氧化酶负调控瘦素表达加剧db/db小鼠心功能异常

目的:分析异丙肾上腺素加剧db/db小鼠心功能损伤的瘦素参与机制及NADPH氧化酶的调控作用。方法:18只野生型小鼠和18只db/db小鼠分别随机分为3组:对照组、异丙肾上腺素组和NADPH氧化酶apocynin组(n均=6)。除对照组外,其余两组小鼠给予异丙肾上腺素皮下注射(1mg/kg),连续6天,apocynin组小鼠第4天起给予apocynin(100mg/kg)灌胃治疗。分析各组小鼠心脏指数,并检测心肌组织中NADPH氧化酶亚基、瘦素及基质金属蛋白酶(MMP)和抑制剂表达。结果:与对照组比较,异丙肾上腺素组小鼠心功能明显异常(P0.01),且NADPH氧化酶亚基p22phox、p47phox、p67phox、gp91phox及瘦素表达明显升高(P0.01),MMP2/9和TIMP1/2也明显升高(P0.01),而apocynin组小鼠上述指标异常得到明显改善(P0.01)。结论:异丙肾上腺素通过下调NADPH氧化酶负调控瘦素表达加剧db/db小鼠心肌功能异常。     

丹参酮Ⅱ_A磺酸钠对心肌钙反常的保护作用

豚鼠离体心脏灌流造成心肌钙反常模型,以丹参酮Ⅱ_A磺酸钠(DS-201)为保护剂,测定心肌组织蛋白释放和钙摄取量,观察作用效果。并与已知钙拮抗剂异搏定比较,探讨DS-201的钙拮抗作用。实验结果表明,DS-201对心肌钙反常损伤具有明显的保护作用,抑制钙内流,减轻钙反常过程中心肌组织钙沉积和心肌损伤所致的蛋白(酶)释放(P<0.01)。该作用在一定范围内具有剂量依赖关系。30mg/L、40mg/LDS-201分别能降低心肌组织蛋白释放量52.8%、66.2%,降低钙摄取量25.8%、36.9%。作用效果优于异搏定,后者降低蛋白释放量47.5%,降低钙摄取量23.9%。     

降钙素基因相关肽对大鼠心肌缺血损伤的影响

目的:观察降钙素基因相关肽对大鼠缺血心肌的保护作用。方法:用单剂量异丙肾上腺素皮下注射复制大鼠心肌缺血损伤模型,单剂量降钙素基因相关肽静脉注射治疗,2 h后采血测定血清心肌酶及血清MDA、SOD水平,同时取心肌组织匀浆测组织MDA、SOD水平,并观察心肌组织结构改变。结果:(1)异丙肾上腺素致缺血心肌损伤大鼠血清和心肌组织MDA升高、SOD下降,而CGRP治疗能逆转上述改变(P＜0.05)。(2)CGRP治疗组心肌酶CK、LDH明显低于损伤组(P＜0.05)。(3)心肌光镜、电镜结果示CGRP组细胞损伤程度明显低于损伤组(P＜0.05)。结论:CGRP对异丙肾上腺素所致大鼠缺血心肌有保护作用,抗膜脂质过氧化可能是其重要机制。     

蝮蛇抗栓酶对异丙肾上腺素诱导大鼠心肌梗塞样损伤的保护作用

连续给大鼠胃饲脂肪餐7天,三天后皮下注射150mg/kg异丙肾上腺素(ISP)二次,间隔24小时,复制了大鼠高脂血症、ISP性梗塞样心肌损伤模型,观察蝮蛇抗栓酶对ISP性梗塞样心肌损伤的保护作用。结果表     

心肌缺血的膜损伤及蝮蛇抗栓酶修饰效应的实验研究

本实验以异丙肾上腺素性心肌缺血(ISP-MI)为模型,对心肌膜脂、膜酶及自由基系统三个方面进行了研究,旨在探讨蝮蛇抗栓酶(Svate)对膜损伤的修饰作用。结果发现,大鼠皮下注射异丙肾(ISP,85mg/kg)24h后,心肌膜脂、膜酶及自由基代谢发生明显紊乱,标志着膜损伤的存在。舌下静脉注射Svate(0.25U/kg)治疗组,与单纯缺血组比较,心肌线粒体Ch/PL比降低,膜脂流动性明显恢复;心肌膜脂过氧化产物丙二醛(MDA)下降,谷胱甘肽过氧化物酶(GSH-Px)活力增加,Na~+-K~+-ATPase活力明显升高及Ca~(2+)-Mg~(2+)-ATPase活力恢复正常。以上结果说明,Svate对缺血心肌膜损伤有一定的修饰效应。     

牛磺酸减轻内毒素诱导的大鼠心肌损伤

目的:探讨牛磺酸对内毒素(即脂多糖,LPS)诱导的大鼠心肌损伤的影响。方法:健康雄性Sprague-Dawley(SD)大鼠30只随机分为3组:正常对照组、内毒素模型组及牛磺酸处理组。正常对照组和内毒素模型组大鼠尾静脉注射生理盐水,牛磺酸处理组大鼠尾静脉注射牛磺酸(100 mg/kg),2 h后,内毒素模型组和牛磺酸处理组大鼠腹腔注射LPS(10 mg/kg),正常对照组大鼠腹腔注射生理盐水。注射内毒素6 h后,采集血样品和心肌组织,检测血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)水平;光镜下观察心肌形态学变化;Western blot检测心肌组织磷酸化核因子κB(p-NF-κB)、环氧合酶2(COX-2)、TNF-α、IL-6及血红素加氧酶1(HO-1)的表达。结果:与正常对照组比较,内毒素模型组大鼠血清SOD活性及心肌组织HO-1表达明显降低(P0.01),血清MDA、TNF-α和IL-6水平明显升高(P0.01),心肌组织p-NF-κB、COX-2、TNF-α及IL-6水平明显升高(P0.01)。与内毒素模型组比较,牛磺酸处理组大鼠血清MDA、TNF-α和IL-6水平明显降低(P0.01),牛磺酸处理明显降低心肌组织COX-2、TNF-α、IL-6及p-NF-κB水平(P0.01),血清SOD活性及心肌组织HO-1表达明显提高(P0.01)。组织学观察显示内毒素模型组大鼠心肌组织有炎症细胞浸润,心肌纤维排列疏松不规则,而正常对照组和牛磺酸处理组大鼠心肌纤维排列整齐规则。结论:牛磺酸预处理能减轻内毒素诱导的心肌损伤,其机制可能通过HO-1/CO信号下调p-NF-κB/COX-2而发挥作用。     

心肌缺血的膜损伤及腹蛇抗栓酶的修饰效应的实验研究

本实验以异丙肾性心肌损伤(PSP-MI)为模型,对心肌膜脂、膜酶及自由基系统三个方面进行了研究,旨在探讨膜损伤在心肌缺血中的意义及蝮蛇抗栓酶(Svate)对其修饰作用。结果发现,大鼠皮下注射异丙肾(ISP,85mg/kg)24h后,与正常对照组比较,心肌游离脂肪酸(FFA)含量明显增加(P<0.05),线粒体胆固醇/磷脂比     

异丙肾性心肌梗死大鼠钙敏感受体的表达和凋亡通路的变化

目的：观察钙敏感受体（CaSR）在异丙肾性心肌梗死大鼠的表达和凋亡通路的变化。方法: 采用连续2 d大剂量异丙肾上腺素（200 mg/kg）皮下注射制备大鼠心肌梗死模型。Wistar大鼠随机分为3组：正常对照组（control）;异丙肾上腺素1 d组(ISO/1d);异丙肾上腺素2 d组（ISO/2d）。采用RT-PCR和Western blotting分别观察CaSR、bax、〖STBX〗bcl-2〖STBZ〗、caspase-3 mRNA和蛋白表达;TUNEL染色观察心肌细胞凋亡情况;光镜和电镜分别观察心肌形态学和超微结构变化;紫外分光法检测乳酸脱氢酶（LDH）、肌酸激酶（CK）、超氧化物歧化酶（SOD）活性和丙二醛(MDA)含量,电化学免疫发光法检测肌钙蛋白（cTnT）水平。结果: 与正常组比较,ISO/1d组：LDH 和CK活性、cTnT水平和MDA含量、细胞凋亡指数以及CaSR、Bax和caspase-3的表达均达高峰,同时SOD活性降低,Bcl-2表达减少,心肌细胞超微结构损伤严重;ISO/2d的心肌损伤指标较ISO/1d组有所减轻。结论: CaSR表达增多可能参与了异丙肾性大鼠心肌梗死的发生,其机制与氧化应激和细胞凋亡有关。     

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.