动脉粥样硬化进程中血脂、血流动力学指标和血管内膜的动态变化

为了建立兔高脂血症及动脉粥样硬化（AS）斑块模型，观察AS斑块形成的动态变化，采用高胆固醇饲料喂养法与免疫反应损伤法结合制备兔高脂血症及AS斑块模型。将45只新西兰兔分成对照组和高脂血症模型组，按照建模时间4、8、12周，又将对照组和模型组分别分为3组。分别于4、8、12周，处死对照组和高脂血症模型组，测定了血脂、血流动力学指标，观察了血管内膜的变化。结果表明：（1）高脂饲养4、8、12周后模型组兔血清中的TC含量显著升高，TG含量在高脂饲养8周开始有明显升高，HDL—C的含量比对照组HDL-C含量要高，但是随造模时间有下降的趋势，LDL—C的含量随造模时间显著升高；（2）血液黏度在高脂模型12周时0．512S^-1和5．96S^-1下，与对照组比较增高显著，颈总动脉血流量和收缩压（BSP）在造模时间8、12周时比对照组有显著增加，而血浆黏度和血管外径随造模时间变化不明显；（3）石蜡切片HE染色，光学显微镜下观察，正常对照组血管内膜光滑，4周模型组内膜有轻微增厚，有少量含脂质的泡沫细胞，8、12周模型组内膜均有明显增厚，并有多层含脂质的泡沫细胞。透射电镜观察，内皮下有沉积形成的脂质空泡。（4）采用免疫组化的方法鉴定了AS斑块处平滑肌细胞源性的泡沫细胞。结果显示：血脂不同组分的变化可以对AS进程起到预示作用；在AS进程中伴随血流动力学因素颈动脉血流量增加、血压升高和低切变率下血液黏度升高；血管内膜不断增厚，AS斑块的成分也会发生变化。     

早期稳定型动脉粥样硬化斑块模型兔损伤区拉曼光谱特征及旋转手法的影响

背景：研究普遍认可颈椎旋转手法可增加颈动脉粥样硬化不稳定型斑块脱落的风险,然而该手法对颈动脉粥样硬化早期稳定型斑块的影响研究甚少。 目的：探索颈椎旋转手法对动脉粥样硬化斑块模型兔脂质含量的影响。 方法：将30只雄性新西兰兔经普通饲料喂养15 d后,随机选取10只作为对照组,继续以普通饲料喂养至18周。剩余20只改用含2%胆固醇、10%猪油和88%普通颗粒饲料的高脂饲料喂养至18周,建立早期稳定型动脉粥样硬化斑块动物模型。高脂饲料喂养14周时,将高脂饲料喂养实验兔随机分为颈椎旋转手法组和模型组,各10只。颈椎旋转手法组兔施行颈椎旋转手法,左右各旋转1次(手法以兔子颈椎旋转至极限即止),1次/3 d,共5次。 结果与结论：对照组兔拉曼光谱图上未见明显的1 450 cm-1及1 660 cm-1脂质特征峰,颈椎旋转手法组和模型组兔动脉粥样硬化斑块均有明显的1 450 cm-1及1 660 cm-1脂质特征峰,但颈椎旋转手法组和模型组特征峰的相对强度差异无显著性意义(P > 0.05)。说明在颈动脉粥样硬化病变早期,短期内施用颈椎旋转手法并不会增加模型兔颈动脉粥样硬化斑块的脂质含量。中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

兔动脉粥样硬化易损斑块模型的建立

目的利用血管内超声(IVUS)的影像学特点分析建立的兔模型的易损斑块。方法16只雄性新西兰纯种兔,通过球囊损伤腹主动脉和高脂(1%胆固醇)饲料喂养8周,建立动脉粥样硬化易损斑块的兔模型。应用IVUS分别测量腹主动脉同一血管段中多个病变部位及其参考部位的各项指标,然后给予中国斑点蝰蛇毒(CRVV)和组胺药物触发,造成实验性斑块破裂和血栓形成。结果破裂与未破裂斑块相比较,破裂斑块具有较大的偏心性(P<0.05),破裂斑块呈现明显的正性重构,而未破裂斑块主要表现为负性重构。结论IVUS应用于已建立的动脉粥样硬化易损斑块的动物模型上,能够准确地识别动脉粥样硬化易损斑块,为以后实验性大样本研究药物稳定易损斑块的治疗奠定了基础。     

实验性动脉粥样硬化兔脑血管血液动力学研究

目的观察动物模型动脉粥样硬化(atherosclerosis,AS)发生、发展过程中脑血管血液动力学指标(cerebrovascularhemodynamicindex,CVHI)的变化规律。方法新西兰大耳白兔20只,随机分为两组:12只为动脉粥样硬化模型组,给予高脂饲料喂养;8只为对照组,给予普通基础饲料喂养。于12周末检测所有兔CVHI,同期进行病理检查,并观察离体血管的顺应性。结果与对照组比较,AS模型组兔的最大血流速度和最小血流速度均有明显降低;而外周阻力、特性阻抗和脉搏波波速明显升高;血管顺应性明显降低。病理结果显示,AS模型组兔的颈动脉粥样硬化斑块形成明显,管腔狭窄。结论CVHI能正确反映颈动脉病变和脑血管病理生理变化,对早期脑动脉粥样硬化的诊断具有重要的意义。     

新西兰兔糖尿病肾病模型的建立方法

目的: 探讨小剂量四氧嘧啶(ALX)建立新西兰兔糖尿病肾病(diabetic nephropathy,DN)模型的可行性。方法: 雄性新西兰兔20只,8只为对照组,给予常规饲料,12只为糖尿病组,给予高糖高脂饮食(常规饲料加5%蔗糖、5%猪油和1%胆固醇)喂养2周,再加用小剂量ALX耳缘静脉注射,分别检测造模前与造模12周后兔血糖、血脂、尿蛋白和肾功能指标,并于12周后进行组织形态学观察。结果: 建模成功动物具有"多饮、多食、多尿、体重减轻"的特点,并出现DN相应的形态及功能改变。结论: 高脂高糖饮食加ALX药物诱导的方法,12 周时可成功制备新西兰兔2型DN模型。     

过氧化物酶体增殖物激活受体γ对血管平滑肌细胞增殖和动脉粥样硬化形成的影响

目的观察过氧化物酶体增殖物激活受体γ(PPARγ)在动脉粥样硬化形成中的作用,检测其对血管平滑肌细胞(VSMC)增殖的影响,探讨其抗AS的分子机制。方法高脂饮食制作兔动脉粥样硬化模型,石蜡切片HE染色检测AS病变程度。MTT法测定VSMC增殖率,Westernblot检测PPARγ和MMP-9蛋白含量。结果高脂喂养导致兔血清中TC、TG和LDL水平升高,AS斑块形成,吡格列酮可对抗高脂饮食诱导的AS。主动脉粥样斑块中的PPAR-γ蛋白表达较对照组显著增多。吡格列酮可抑制AngⅡ诱导的VSMC增殖,并使高脂喂养的兔主动脉和VSMC中的MMP-9表达减少。结论PPARγ是调节AS的关键分子,被激动剂吡格列酮激活后可能通过下调MMP-9的表达,抑制VSMC的增殖而起到抗AS的作用。     

氯沙坦对动脉粥样硬化兔的MCP-1及基因表达的实验研究

为了探讨血管紧张素Ⅱ的Ⅰ型受体(AT1R)拮抗剂氯沙坦(Losartan)的抗动脉粥样硬化(AS)作用及观察其是否能抑制单核细胞趋化蛋白-1(MCP-1)的蛋白及基因表达,我们通过高脂饮食及内皮损伤术建立兔AS模型,一组用Losartan(25mg/kg/d),另一组不用,喂养4个月,观察血管内膜的变化;同时做免疫组化及原位杂交,分别观察MCP-1蛋白及基因的表达。结果发现Losartan治疗组兔主动脉内膜面积及内、中膜面积之比均小于未治疗组,其MCP-1的蛋白及mRNA的表达亦明显减少,表明Losartan可通过抑制MCP-1的产生而具有抗AS作用。     

兔动脉粥样硬化血管成形术后再狭窄模型的建立与改良*

 目的：探讨建立兔动脉粥样硬化血管成形术后再狭窄模型的有效方法。方法：30只雄性新西兰大白兔,随机分成3组,即空白对照组、下肢动脉切开组及下肢动脉穿刺组,每组10只。空白对照组仅行高脂饲料喂养,另外2组高脂饲料喂养1周后行下肢动脉穿刺或切开行髂动脉内膜剥脱术,继续高脂饲料喂养4周,下肢动脉穿刺组再次穿刺股动脉行髂动脉球囊成形术,下肢动脉切开组经颈动脉切开行髂动脉球囊成形术。3组均普通饲料喂养4周,计算每天进食饲料量,采血化验血脂,取病变段血管行苏木精-伊红染色及图像工作站对血管造影结果行血管狭窄分析。结果：下肢动脉切开组进食饲料量减少,血清总胆固醇和低密度脂蛋白胆固醇显著低于对照组。3组动物均出现下肢动脉粥样硬化,其中下肢动脉穿刺组及下肢动脉切开组内膜显著增厚,管腔狭窄。动脉穿刺组与动脉切开组血管面积狭窄率及直径狭窄率与对照组相比差异显著(P<0.01)。结论：下肢动脉穿刺与球囊损伤、球囊血管成形术结合可成功建立兔动脉粥样硬化血管成形术后再狭窄模型,方法简单,可重复性强,较下肢动脉切开术更适合血管成形术后再狭窄模型的建立。     

ACI患者联检AT-Ⅱ与hs-CRP的结果评价

急性脑梗死(ACI)多发生在动脉粥样硬化(AS)的基础上,常伴纤溶系统功能失调或障碍。研究表明[1],AS及其血栓性病变不仅仅是脂质沉积,而且也是血管炎症反应,血管内皮的炎症反应不仅是压力损伤的生化结果,同时也是AS及斑块形成的启动因子,故学界有"无炎症、无动粥"(动脉粥样硬化)之说。文献报道[2],血管紧张素-Ⅱ(AT-Ⅱ)和hs-     

CD40-CD40L与急性冠状动脉综合征的研究进展

急性冠状动脉综合征（Acute Coronary Syndrome，ACS）是心肌急性缺血的一组临床表现，包括不稳定心绞痛，无ST段抬高的急性心肌梗死和有ST段抬高的急性心肌梗死，也包括猝死性冠心病。目前认为ACS的病理生理机制是粥样硬化斑块不稳定，发生溃破、出血，随后血栓形成，引起冠状动脉不同程度堵塞，造成心肌血和氧供应急剧减少。免疫和炎症反应在ACS的发生发展过程中起着重要作用，CIM0-CD40L作为免疫和炎症反应中的重要信号转导系统，在动脉粥样硬化（Atherosclerosis，AS）炎症调节中的作用已日益明确，它几乎贯穿AS发生发展乃至斑块破裂的全过程。Yan等最近报道，ACS患者血小板表面CD40、CD40L显著升高，且不稳定型心绞痛病人的CD40、CD40L水平显著高于稳定型心绞痛病人；Wu等在兔AS模型中发现CD40、CD40L也显著升高，且与斑块中基质金属蛋白酶（Matrix Metalloproteinases，MMPs）成线性相关；Schonbeck证实CD40共刺激信号在AS鼠的血管内皮及斑块中大量表达，且抑制CD40信号系统，限制AS的进展。故认为CD40、CD40L对斑块不稳定性及ACS的发展起一定作用。     

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.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

HLA genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

État de l’art : nouveaux anticoagulants et transfusion

Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. We propose an update on DOAC-associated bleeding management, integrating the availability of idarucizumab and the critical place of DOAC concentration measurements.     

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.     

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.     

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.