四逆汤改善缺血心肌能量代谢的作用及其机制探讨

目的：探讨四逆汤改善缺血心肌能量代谢的作用及其机制。方法：垂体后叶素性小鼠心肌缺血模型，四逆汤（浓度１０３ｇ生药／Ｌ）灌胃，剂量０１ｍＬ／２０ｇｗｔ·ｄ－１，心肌超微结构用电镜观察分析，心肌ＡＴＰ含量用高效液相色谱法测定，乳酸浓度用常规生化方法测定。结果：与缺血组相比，四逆汤组缺血心肌线粒体损伤显著减轻（Ｐ＜００５），糖原消耗显著减少（Ｐ＜００５），乳酸浓度显著下降（Ｐ＜００５），心肌营养血流量显著上升（Ｐ＜００１），氧自由基浓度显著降低（Ｐ＜００１）。结论：四逆汤具有显著改善缺血心肌能量代谢的作用，该作用与其增加心肌供血和清除氧自由基有关     

缺血再灌注时大鼠心肌局部血管紧张素Ⅱ的变化及其与能量代谢的关系

本实验用高效液相色谱法测定了不同缺血／再灌注条件下心肌组织内高能磷酸化合物的含量，并用放色法测定了大鼠心肌组织内血管紧张素Ⅱ（ＡＴ－Ⅱ）的含量。结果表明：缺血３０ｍｉｎ和缺血４０ｍｉｎ组ＡＴ－Ⅱ明显高于缺血１５ｍｉｎ组（Ｐ＜０．０５），再灌后ＡＴ－Ⅱ含量进一步升高，此变化与在缺血再灌注过程中的高能磷酸化合物改变恰好相反。在缺血４０ｍｉｎ再灌２０ｍｉｎ组的灌流液中预先加入血管紧张素转换酶抑制剂－巯甲丙脯酸，则心肌中磷酸肌酸（ＰＣｒ）、三磷酸腺苷（ＡＴＰ），ＴＡＮ（ＡＭＰ＋ＡＤＰ＋ＡＴＰ）与能荷Ｅ（１／２ＡＤＰ＋ＡＴＰ／ＴＡＮ）均非常显著高于未加巯甲丙脯酸组（Ｐ＜０．００１），可见心肌缺血／再灌注时心肌高能磷酸化合物含量的变化与肾素－血管紧张素系统关系密切，两者呈显著负相关（ｒ＝－０．８３）。抑制ＡＴ－Ⅱ的生成能有效地保护缺血心肌的能量贮备     

抗疲劳1号对游泳大鼠血液、肌肉和脑中ATP含量及血乳酸含量的影响

目的：观察抗疲劳１号（ＡＦ－１）对游泳运动大鼠血液ＡＴＰ和乳酸，以及脑和肌肉组织中ＡＴＰ含量的影响。方法：用生物发光法测定６组不同游泳强度大鼠血液和组织中ＡＴＰ含量；血乳酸含量变化用乳酸自动分析仪监测。结果：给药组大鼠游泳１０ｍｉｎ，血中ＡＴＰ含量明显高于对照组；血中乳酸含量明显低于对照组（Ｐ＜００１）。在游泳力竭鼠中，给药组血ＡＴＰ含量也较对照组高；而血乳酸含量较对照组低（Ｐ＜００５，Ｐ＜００１）。给药大鼠中，游泳１０ｍｉｎ组肌肉ＡＴＰ含量明显高于对照组（Ｐ＜００１）；游泳力竭组仍可保持在对照组水平（游泳时间不同）。给药鼠游泳１０ｍｉｎ和力竭两组脑组织中ＡＴＰ含量与未给药动物无明显差异，但未游泳组明显高于对照组。未游泳给药鼠肌肉中ＡＴＰ含量也明显高于对照组（Ｐ＜００５，Ｐ＜００１）。结论：抗疲劳１号具有抗疲劳功用，可能通过增加组织ＡＴＰ的生成和贮存，促进能量代谢，减少乳酸堆积，进而增加运动强度及运动时间     

大鼠压力超负荷早期心肌收缩功能和环核苷酸的动态反应

目的：探讨大鼠压力超负荷后心肌力学及环核苷酸的变化规律。方法：颈总动脉插管法动态测定腹主动脉部分缩窄大鼠心肌力学及环核苷酸含量（放免法）的变化。结果：伴随动脉血压的升高,手术组大鼠心肌收缩功能于术后４ｈ暂时性增强（与对照组比较,Ｐ＜００１）,之后逐渐降低,术后第５ｄ降至最低,其后逐渐恢复正常。心肌ｃＡＭＰ含量于术后３０ｍｉｎ显著升高（Ｐ＜００５）,第５ｄ时达最高（Ｐ＜００１）,之后逐渐下降,第３０ｄ时恢复正常,而ｃＧＭＰ变化正相反。小剂量巯甲丙脯酸可减轻手术大鼠早期及此后的心肌收缩功能受抑,但对环核苷酸含量无显著影响。结论：大鼠压力超负荷早期心肌收缩功能受抑,心肌ｃＡＭＰ浓度呈急性代偿性升高后逐渐恢复正常,而ｃＧＭＰ变化相反。     

内毒素大鼠休克早期血浆组织因子与组织因子途径抑制物的观察

目的：观察内毒素休克早期大鼠血浆ＴＦ、ＴＦＰＩ的变化。结果：静脉给予内毒素的大鼠ＭＡＰ呈进行性下降，至１２０ｍｉｎ时降至（５８±２５）ｋＰａ，ＴＦ含量高于对照组（Ｐ＜００５），而ＴＦＰＩ无显著改变（Ｐ＞００５）。血浆ＴＮＦ含量明显增高（Ｐ＜００１），ＡＴⅢ活性显著低于对照组（Ｐ＜００１）；ＷＢＣ计数减少（Ｐ＜００１），ＰＬ计数无明显改变（Ｐ＞００５）。结论：内毒素休克早期休克组织因子凝血途径易化因素增强，而拮抗因素不变或减弱     

大鼠脑缺血及再灌流对脑组织血流量、ATP和乳酸水平含量的影响

目的和方法：本研究采用大鼠可逆性阻塞大脑中动脉所致的局灶性脑缺血再灌流模型，观察缺血３ｈ再灌流３ｈ、缺血６ｈ再灌流３ｈ对脑组织脑局部血流量（ｒｅｇｉｏｎａｌｃｅｒｅｂｒａｌｂｌｏｏｄｆｌｏｗ，ｒＣＢＦ）、ＡＴＰ、乳酸及脑水含量的影响。结果：缺血３ｈｒＣＢＦ明显下降（Ｐ＜００１），再灌流３ｈ升至缺血前６５３％（Ｐ＜００１）。缺血３ｈ再灌流３ｈ与缺血６ｈ组比较，ＡＴＰ明显恢复（Ｐ＜００１），乳酸含量明显下降（Ｐ＜００１），脑水含量明显减少（Ｐ＜００５）。缺血６ｈ再灌流３ｈ与缺血９ｈ组比较，尽管ＡＴＰ明显恢复（Ｐ＜００１），乳酸含量下降（Ｐ＜００１），但脑水含量无显著差异（Ｐ＞０１）。结论：缺血３ｈ再灌流３ｈ保护“半暗带”的效果优于缺血６ｈ再灌流３ｈ。     

飞龙掌血水提物对垂体后叶素所致大鼠缺血心肌的保护作用

目的：观察飞龙掌血水提物（Ｆ０１）对急性缺血心肌的保护作用。方法：采用垂体后叶素所致大鼠急性心肌缺血模型观察药物的作用。结果：Ｆ０１（１７５或３００ｍｇ／ｋｇ）及维拉帕米在大部分时点上能明显缓解垂体后叶素所引起的心电图Ｔ波变化（Ｐ＜００５或Ｐ＜００１）。垂体后叶素使对照组１００％的动物发生心律失常，而在Ｆ０１组（１００、１７５或３００ｍｇ／ｋｇ）及维拉帕米组中，心律失常的发生率分别为７０％（Ｐ＞００５）、４４％（Ｐ＜００５）、２０％（Ｐ＜００１）和１１％（Ｐ＜００１）。结论：Ｆ０１对垂体后叶素所致急性缺血心肌具有保护作用，其效应与剂量呈相关性。     

体外反搏治疗失血性休克中一氧化氮合酶的变化

目的：探讨反搏治疗失血休克中一氧化氮合酶（ＮＯＳ）的变化。方法：复制狗的失血休克模型，用同位素方法测定反搏前后各组织的ＮＯＳ活性。结果：体外反搏后平均动脉压较反搏前明显上升（Ｐ＜００１）。脑ＮＯＳ测定值假手术对照组明显高于失血休克组Ｐ＜００１）及失血休克克反搏组（Ｐ＜００１），失血休克组则明显低于失血休克反搏组（Ｐ＜００１）；心肌ＮＯＳ活性假手术对照组与失血休克反搏组均明显高于失血休克组（Ｐ＜００５，Ｐ＜００１），但假手术对照组与失血休克反搏组之间无显著差异（Ｐ＞００５）；主动脉ＮＯＳ活性假手术对照组明显高于失血休克组（Ｐ＜００１）及失血休克反搏组（Ｐ＜００５），但失血休克组与失血休克反搏组间无明显差异（Ｐ＞００５）。结论：体外反搏可以增强小血管ＮＯＳ活性，ＮＯＳ活性的恢复则可能在反搏治疗中起重要作用     

α—MSH对家兔ET性发热反应及脑腹中隔区AVP含量的影响

目的：研究脑腹中隔区精氨酸加压素（ＡＶＰ）在α－黑素细胞刺激素（αＭＳＨ）解热机制中的作用。方法：建立家兔ＥＴ性发热模型，观察侧脑室注射α－ＭＳＨ对家兔ＥＴ性发热反应及脑腹中隔区ＡＶＰ含量的影响。结果：（１）静脉注射ＥＴ（０３μｇ／ｋｇ）引起家兔明显的发热反应（Ｐ＜０００１），并增加脑腹中隔ＡＶＰ含量（Ｐ＜００５）；（２）静脉注射ＥＴ（０３μｇ／ｋｇ）３０ｍｉｎ后，侧脑室注射α－ＭＳＨ（２００ｎｇ／只），能明显抑制家兔发热反应，同时脑腹中隔区ＡＶＰ含量进一步显著增高（Ｐ＜０００１）；（３）侧脑室注射α－ＭＳＨ（２００ｎｇ／只）并不影响家兔正常体温，但增加脑腹中隔区ＡＶＰ含量（Ｐ＜００５）。结论：α－ＭＳＨ的解热作用可能部分是通过腹中隔ＡＶＰ增多来实现的，αＭＳＨ可能是引起发热时脑腹中隔区ＡＶＰ含量增加的一个重要因素。     

心肌顿抑时红细胞变形性变化机理及其意义初探

目的和方法：本文通过一次性阻断兔冠脉左室支１５ｍｉｎ后再灌注复制在体心肌顿抑（ＭＳ）模型，动态观察心肌缺血前后红细胞变形指数（ｄｅｆｏｒｍａｂｉｌｉｔｙｉｎｄｅｘ，ＤＩ）、红细胞超氧化物歧化酶（ｓｕｐｅｒｏｘｉｄｅｄｉｓｍｕｔａｓｅ，ＳＯＤ）活力、红细胞ＡＴＰ、红细胞丙二醛（ＭＤＡ）含量和心功能参数（左室舒张末压、左室收缩压±ｄｐ／ｄｔｍａｘ）变化。结果：缺血末心功能下降最显著（Ｐ＜００１）；再灌注０５ｈ时ＭＤＡ明显升高，而ＤＩ、ＳＯＤ明显下降（Ｐ＜００１）。随继续再灌注上述指标逐渐恢复。各时点ＡＴＰ无明显变化。再灌注０５ｈ时红细胞ＭＤＡ与ＤＩ、ＳＯＤ均呈显著负相关（Ｐ＜００１），ＤＩ与＋ｄｐ／ｄｔｍａｘ正相关（Ｐ＜００５）。结论：ＭＳ早期红细胞变形性降低与暂时性氧化－抗氧化失衡有关；再灌注早期红细胞变形性降低可能参与ＭＳ早期发生机制     

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.     

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.     

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.     

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.     

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.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'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.