糖尿病肾病防治新观点--美国第84届内分泌协会年会专题小结

糖尿病肾病是导致糖尿病死亡及终末期肾病透析的主要原因之一。在美国第84届内分泌协会年会上报告了一些糖尿病肾病治疗新观点。内容包括：HOPE研究结果；血管紧张素转换酶抑制剂(ACEI)是糖尿病患者心血管甚至是肾功能不全的保护药；ACEI可能能够预防糖尿病；血管紧张素1(AT1)受体阻滞剂(ARB)肾保护作用的证据；糖尿病中血压控制的重要性；ARB改善这些患者充血性心力衰竭及使用ACEI和ARB的临床建议等。本文对此作一综述。     

ARB联合ACEI治疗糖尿病肾病60例临床疗效分析

目的 观察联合使用血管紧张素受体拮抗剂(ARB)和血管紧张素转换酶抑制剂(ACEI)治疗糖尿病肾病患者的疗效及安全性.方法 选取确诊的糖尿病肾病患者60例,根据对ACEI治疗的顺应性分为ARB组(n=20)、ACEI组(n=20)和ACEI+ARB组(n=20),疗程6个月,观察24h尿蛋白定量、血压、血肌酐.结果 三组药物均能显著降低糖尿病肾病患者血压(P＜0.05),组间差异无显著性(P＞0.05);ACEI+ARB联合用药组患者24h尿蛋白定量减少更显著(P＜0.01 vs 单纯使用ACEI或ARB组P＜0.05).结论 三组药物均能良好控制患者血压,降压效果三组间差异无显著性;但ACEI+ARB联合用药可延缓糖尿病肾病进展,较分别单纯使用这两种药物对肾功能的保护作用更明显.     

ACEI及ARB对寒冷所致的高血压病人循环系统反应的干预

目的为了探讨血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体阻滞剂(ARB)对寒冷所致的高血压病人循环系统反应的影响. 方法 111例血压控制稳定的高血压病人分成ACEI治疗、ARB治疗组及对照组3组,观察气温骤降前后血压和心率变化. 结果①3组病人气温骤降前血压控制均达到目标血压;②气温骤降后,ARB治疗组收缩压、舒张压无明显上升,其余各组收缩压、舒张压均明显上升;心率3组均无明显变化;③与对照组比较,ARB组寒冷所致的收缩压上升幅度明显减少;④与对照组比较,ACEI及ARB组寒冷所致的舒张压上升均轻度减少(p>0.05),但无统计差异,心率变化亦无差异. 结论 ACEI未能有效地阻断高血压病人寒冷所致的循环系统反应,亦不比其它降压药优胜;但ARB能有效地阻断高血压病人寒冷所致的循环系统反应,且明显优胜于其它降压药.     

ACEI及ARB对寒冷所致的高血压病人循环系统反应的干预

目的 为了探讨血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB）对寒冷所致的高血压病人循环系统反应的影响。方法 111例血压控制稳定的高血压病人分成ACEI治疗、ARB治疗组及对照组3组，观察气温骤降前后血压和心率变化。结果 ①3组病人气温骤降前血压控制均达到目标血压；②气温骤降后，ARB治疗组收缩压、舒张压无明显上升，其余各组收缩压、舒张压均明显上升；心率3组均无明显变化；③与对照组比较，ARB组寒冷所致的收缩压上升幅度明显减少；④与对照组比较，ACEI及ARB组寒冷所致的舒张压上升均轻度减少（P＞0．05），但无统计差异，心率变化亦无差异。结论 ACEI未能有效地阻断高血压病人寒冷所致的循环系统反应，亦不比其它降压药优胜；但ARB能有效地阻断高血压病人寒冷所致的循环系统反应，且明显优胜于其它降压药。     

ACEI和ARB治疗改善糖尿病大鼠胰岛素分泌功能的研究

目的：研究血管紧张素转换酶抑制剂ACEI和血管紧张素II受体拮抗剂ARB对高脂喂养链脲佐菌素（STZ）诱导的糖尿病大鼠胰岛素和胰高糖素分泌及氧化应激功能的影响。方法：应用Enalaprial和Losartan对高脂喂养STZ诱导的糖尿病大鼠进行干预,放免法测定胰岛素和胰高糖素,ELISA检查氧化应激指标8-isoPGF-2α水平。并通过静脉葡萄糖耐量实验了解ACEI和ARB治疗对一相胰岛素分泌的影响。结果：ACEI或ARB治疗可以减少氧化应激,保护一相胰岛素分泌。结论：ACEI或ARB治疗对维持正常的胰岛素分泌可能起到了重要保护作用,从而降低血糖和减少糖尿病的发生。这可能是大规模临床研究中ACEI和ARB使血糖回归至正常水平或减少新发的糖尿病的发生率的深层机制之一。     

血管紧张素ⅡⅠ型受体拮抗剂和血管紧张素转换酶抑制剂的肾保护作用及其对肾内肾素-血管紧张素系统的影响

目的:比较血管紧张素受体拮抗剂(AT₁RA)和血管紧张素转换酶抑制剂(ACEI)的肾脏保护作用,观察这两类药物对肾脏局部肾素-血管紧张素系统的影响。方法:肾病综合征模型由反复给SD大鼠腹腔注射嘌呤霉素诱导而成。28只大鼠随机分为4组:正常对照组、肾病对照组、AT₁RA治疗组和ACEI治疗组。12周后收集血、尿和肾组织标本进行检测。结果:两治疗组尿蛋白明显少于肾病对照组,且到实验期末,肾功能仍在正常范围,肾小球和肾间质损伤指数也低于肾病对照组,但两治疗组间无明显差异(P＞0.05)。肾病对照组的肾组织ACE活性、血管紧张素Ⅱ浓度显著高于正常对照组(P＜0.01)。在ACEI和AT₁RA治疗组,肾组织ACE活性和ANGⅡ浓度显著低于肾病对照组(P＜0.01)。结论:AT₁RA和ACEI在肾病综合征进行性肾损伤中,具有相似的肾脏保护作用,这种作用可能与抑制肾脏局部的ANGⅡ有关。     

洛丁新对不同时期糖尿病肾病患者血浆内皮素的影响

洛丁新是第三代血管紧张素转换酶抑制剂(ACEI)。近年来发现,ACEI具有降低肾小球毛细血管压,改善肾小球灌注状态,减少尿蛋白的排泄,保护肾脏,延缓糖尿病肾病(DN)进展的作用[1] 。我们通过观察不同时期DN患者服用洛丁新治疗前后血浆内皮素水平变化,探讨洛丁新对其的影响。1　对象     

心肌细胞钙通道的调控

本文扼要介绍心肌细胞钙通道的调控机制。儿茶酚胺、心纳素、血管紧张素Ⅱ、甲状旁腺激素及二氢吡啶衍生物等药物和某些调节物对心肌钙通道有影响。     

钙通道阻滞剂治疗心衰的疗效和安全性——第二代二氢吡啶类近期临床试验荟萃分析

背景　获得 ACEI、利尿剂、地高辛治疗的心衰仍有很高的致残率和死亡率。钙通道阻滞剂扩张血管被认为有潜在益处。然而 ,包括二氢吡啶 ,尼非地平的第一代钙阻断剂 ,在心衰的治疗中表现出令人失望的结果。大家都希望第二代二氢吡啶类及所有的钙阻滞剂更有价值 ,它们是近年慢性心衰研究的热点。方法和结果　资料来源于 Medline数据库自 1990年来有关二氢吡啶类心衰治疗研究 ,共 17个研究 2 0 0 0多例患者 ,不论血浆神经激素是否受影响 ,患者的运动耐受力及心功能均无可靠的受益。另一方面 ,第二代二氢吡啶类钙通道阻滞剂总体上未使心衰恶化…     

血管紧张素II受体拮抗剂与肾脏病

血管紧张素II对慢性肾脏疾病进展具有重要作用 ,血管紧张素II的I型受体拮抗剂可阻断血管紧张素II的作用 ,有可能性成为一类新的肾脏保护药物。本文从动物实验和临床研究方面总结血管紧张素II受体拮抗剂对肾脏病的作用。     

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.     

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.     

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.     

'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.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.