衰竭心肌能量代谢重构及β3肾上腺素能受体、过氧化物酶体增殖物激活受体α表达变化的研究

目的 通过检测衰竭与健康心肌组织代谢底物含量、相关酶活性及β3肾上腺素能受体、过氧化物酶体增殖物激活受体α（PPARα）基因和蛋白表达的变化,探讨衰竭心肌代谢重构的表现及可能机制。方法 选取6例意外伤亡健康者心肌组织和20例心外科瓣膜置换术的心力衰竭患者,检测心肌游离脂肪酸（FFA）、乳酸（LD）含量和ATP酶活力。应用逆转录聚合酶链反应、Western blot和免疫组化法分别检测心肌组织β3受体和PPARα mRNA表达以及蛋白和定位。结果 衰竭心肌FFA和LD含量明显增加（P〈0．01和P〈0．05）。Na^＋K^＋-ATP酶和Ca^2＋Mg^2＋-ATP酶活性则显著降低（P〈0．05和P〈0．01）。衰竭心肌β3肾上腺素能受体mRNA和蛋白表达明显高于正常心肌,而PPARα表达则显著低于正常心肌,但并未发生定位变化。结论心力衰竭时存在代谢重构,表现为心肌代谢底物发生转变,代谢相关酶活性下降等,β3肾上腺素能受体和PPARα在衰竭心肌分别上调和下调,可能参与心肌组织代谢重构。     

甲状腺功能减退大鼠心肌抗氧化能力及ATP酶活性的实验研究

目的 研究甲状腺功能减退大鼠心肌抗氧化能力及心肌膜标志酶活性的变化，探讨甲状腺功能减退致心肌损伤的发病机制。方法 30只Wistar大鼠随机分为对照组和甲状腺功能减退组，用低碘饲料和不含碘的水喂养大鼠复制甲状腺功能减退动物模型。制备心肌组织匀浆，提取心肌生物膜，测定心肌组织丙二醛（MDA）水平、谷胱甘肽过氧化物酶（GSH—Px）和超氧化物歧化酶（SOD）活性及心肌生物膜Na^＋，K^＋-ATP酶、Mg^2＋-ATP酶、Ca^2＋-ATP酶、Ca^2＋，Mg^2＋-ATP酶活性。结果 与对照组比较，甲状腺功能减退组血清T3、T4均明显下降（P〈0．05或〈0．01）：心肌组织MDA水平和GSH—Px活性明显升高（P〈0．05），而SOD活性明显降低（P〈0．05）；心肌生物膜Na^＋，K^＋-ATP酶、Ca^2＋-ATP酶、Mg^2＋-ATP酶、Ca^2＋，Mg^2＋-ATP酶活性明显下降（P〈0．05）。结论 甲状腺功能减退时心肌抗氧化能力下降，心肌过氧化损伤，表现为心肌膜上参与代谢的ATP酶活性降低。     

老年大鼠心肌PPARα mRNA和IL-1β mRNA表达变化及阿托伐他汀的干预作用

目的进一步探讨心脏衰老的机制及干预因素的影响。方法将30只20月龄的Wistar大鼠随机分为观察1组、观察2组和老年对照组各10只，设10只3月龄大鼠为青年组。观察1组、观察2组分别予阿托伐他汀1、10mg／（kg·d）灌胃，青年组和老年对照组予等体积生理盐水灌胃，均连续4个月。采用RT—PCR方法检测各组心肌过氧化物酶体增殖物激活物受体α（PPARα）mRNA和自细胞介素（IL）-1β mRNA表达水平。结果与青年对照组比较，老年对照组PPARα mRNA表达水平显著降低（P〈0．01），IL-1β mRNA表达水平显著增高（P〈0．01）；与老年对照组比较，观察l组和观察2组PPARα mRNA表达水平显著升高（P〈0．01），IL-1βmRNA表达水平显著降低（P〈0．01），尤以观察2组为著。结论老年大鼠心肌IL-1βmRNA表达显著增高、PPARα mRNA表达显著降低，此可能在心脏衰老发生、发展过程中起重要作用；阿托伐他汀可通过激活PPARα抑制IL-1β异常表达，此可能为其对抗衰老、改善心脏功能的重要机制之一。     

大蒜素对鼠缺血再灌注心肌过氧化物酶体增殖物激活受体α表达的影响

目的：探讨大蒜素对实验性大鼠缺血再灌注心肌梗死面积及过氧化物酶体增殖物激活受体α（PPARα）表达的影响。方法：Wistar大鼠70只被随机分为三组：假手术组（n=24），缺血再灌注组（n=24），大蒜素组（n=22）。采用鼠心冠状动脉左前降支结扎法制作在体缺血再灌注模型，观察心肌梗死范围，运用半定量RT-PCR方法对心肌PPARα mRNA的表达情况进行分析，运用Western—blotting方法对检测PPAR蛋白表达情况。结果：大蒜素组心肌梗死面积显著减少（P〈0．05），并且心肌PPARα mRNA及蛋白表达水平显著上调（P〈0．01）。结论：大蒜素可显著减少实验性大鼠缺血再灌注后梗死面积及并使心肌中过氧化物酶体增殖物激活受体α（PPARα）显著上调。     

阿托伐他汀通过PPARβ／δ信号通路下调衰老心肌TNF-α表达的研究

目的：观察阿托伐他汀下调老年大鼠心肌肿瘤坏死因子-α（TNF-α）表达的作用及其与过氧化物酶体增殖物激活型受体β／δ（PPARβ／δ）信号通路之间的关系。方法：分离培养24个月龄大鼠的心肌细胞,将心肌细胞分为空白对照组、溶剂对照组、阿托伐他汀组、阿托伐他汀＋PPARβ／δ拮抗剂GSK0660组。各组细胞分别加入细胞培养液、二甲基亚砜（DMSO）、阿托伐他汀、阿托伐他汀＋GSK0660处理。用RT—PCR方法检测各组大鼠衰老心肌细胞的TNF-αmRNA表达水平,用westernblot方法检测各组TNF-α蛋白含量。结果：（1）与空白对照组相比,溶剂对照组大鼠衰老心肌细胞的TNF-α mRNA和蛋白水平均无显著差异;（2）与空白对照组相比,阿托伐他汀组的TNF-α mRNA和蛋白水平含量均显著降低（P〈0．01）;（3）阿托伐他汀＋GSK0660组的TNF-α mRNA表达水平及蛋白含量均显著高于阿托伐他汀组,但仍低于空白对照组（P〈0．05）。结论：阿托伐他汀可通过激活PPARβ／δ信号通路下调衰老心肌细胞TNF—d的表达。     

非诺贝特对胰岛素抵抗大鼠肝脏脂肪酸氧化的影响

目的观察自发胰岛素抵抗的OLETF大鼠肝脏脂肪酸氧化代谢的异常以及非诺贝特对其的影响。方法以8周龄LETO大鼠为正常对照,将同周龄OLETF大鼠随机分为未治疗组和治疗组[非诺贝特20ms／（kg·d）],于17周龄及30周龄分批处死动物,使用实时定量RT－PCR法测定肝脏组织脂肪酸氧化相关基因过氧化物酶体增生物激活受体－α（PPAR－α）、丙二酰辅酶A脱羧酶（MCD）、脂酰辅酶A氧化酶（AOX）mRNA的表达。结果与唧0大鼠相比,未治疗组8周龄大鼠首先出现糖负荷后2h游离脂肪酸（FFA）水平升高（P〈0．05）,17周龄出现空腹FFA以及血糖、胰岛素水平的升高;30周龄时肝脏组织PPAR-α、MCD、AOXmRNA表达均下调,甘油三酯含量升高（P均〈0．01）。治疗组空腹FFA水平明显降低,肝组织PPAR-α、MCD、AOXmRNA表达上调,肝组织甘油三酯含量下降（P均〈0．05）。结论非诺贝特可使OLETF大鼠肝脏脂肪含量下降,这可能与其降低血清FFA水平及上调肝脏组织与脂肪酸氧化相关酶的基因表达有关。     

脑缺血和NBP预处理对脑缺血沙鼠NGB和mit-Na+,K+-ATP酶活性的影响

目的探讨丁基苯酞（NBP）对脑缺血沙鼠脑红蛋白（NGB）和线粒体Na^＋,K^＋-ATP（mit-Na^＋,K^＋-ATP）酶活性的影响。方法将蒙古沙鼠66只随机分为假手术组：脑缺血组、NBP预处理组。采用颈总动脉结扎的方法制作脑缺血模型。分别采用免疫组化染色及化学比色法检测NGB阳性细胞数和mit—Na^＋,K^＋-ATP酶活性。结果NBP预处理组NGB表达量在缺血1、10、30rain时较脑缺血组显著增多（P〈0．05）;两组在缺血1、5、30、60min时mit—Na^＋,K^＋-ATP酶活性有统计学差异（P〈0．05）;NBP预处理组mit—Na^＋,K^＋-ATP酶活性与NGB表达量呈负相关（P〈0．01）。结论NBP可促进脑缺血时NGB的表达,维持mit—Na^＋,K^＋-ATP酶活性。     

超重和肥胖人群脂联素受体mRNA的水平与脂肪细胞因子的相关性

目的 了解两种脂联素受体（AdpR1和AdpR2）在人脂肪组织中的表达水平及其与血清脂肪细胞因子的关系。方法 选取19例超重或肥胖（OW＋Ob）和29例正常体重者（NC），用RT-PCR技术检测腹部皮下脂肪组织（AAT）与大网膜脂肪组织（0AT）中脂联素受体的表达水平，并测FIns、血脂和血清脂联素、TNF-α、FFA等指标。结果 （1）两种脂联素受体mRNA的表达水平在OW＋Ob组和NC组、AAT和OAT之间均无差异；但OW＋Ob患者的血浆TG、VLDL-C、FIns、TNF-α、FFA均高于NC组（P＜0．05～P＜0．01），而血清脂联素低于NC组（P＜0．05）。（2）总体观察对象中，AAT的脂联素受体mRNA表达水平与血清脂联素、FFA、FIns、HOMA-IR水平呈负相关（P＜0．05～P＜0．01）；与ISI呈正相关（P分别＜0．05和＜0．01）。（3）OW＋Ob组中脂联素与BMI、FFA、FIns、HOMA-IR呈负相关（P＜0．05～P＜0．01），与ISI呈正相关（P＜0．01）；FFA与血浆TG、LDL-C、FIns呈正相关（P均＜0．05）。结论 OW＋Ob人群的血清TNF-α、FFA水平高于NC人群，脂联素水平低于NC人群，而脂联素受体mRNA的表达水平在两组间没有差异。脂联素受体、FIns、脂联素、FFA是一组很好的评估胰岛素敏感性的指标。     

心力衰竭病人β受体信号相关通路改变

目的探讨心衰病人心肌组织β1、β2、β3受体mRNA表达的变化及其与相关信号通路的关系。方法应用逆转录聚合酶链反应（RT—PCR）方法检测24例瓣膜置换术的心衰病人和5例健康对照者心肌组织β1、β2、β受体mRNA表达。用化学法和放免法测定心肌一氧化氮合酶（NOS）、诱导型NOS（iNOS）、环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）的变化。结果心衰时心肌β1受体mRNA表达下调、cAMP生成减少；β3受体上调、NOS活性增加和cGMP生成增多，β1受体下调和β3受体上调均与心衰严重程度有关，β2受体表达无改变。结论心衰时心脏β受体信号通路中包括β受体mRNA、cAMP、cGMP、NOS等多个环节发生改变，且改变程度与心功能相关。     

山楂叶提取物对非酒精性脂肪性肝病大鼠糖脂代谢作用的研究

目的：观察山楂叶提取物对非酒精性脂肪性肝病（NAFLD）大鼠糖脂代谢的影响。方法：用高脂饲料诱导建立大鼠NAFLD模型,分为正常组、模型组、阳性药物对照组、山楂叶提取物组、自然恢复组和节食组,观察各组大鼠血清中甘油三酯（TC）,总胆固醇（TG）,游离脂肪酸（FFA）,脂蛋白酯酶（LPL）、空腹血糖（FBG）、空腹胰岛素（INS）和胰岛素抵抗指数（IRI）以及大鼠肝脏组织过氧化物酶体增殖物激活受体α（PPARα）mRNA的表达情况及其肝组织病理学改变情况。结果：与模型组和自然恢复组相比,山楂叶提取物组大鼠体重明显降低,血清TC、FFA、FPG、INS、IRI明显降低（P〈0．05）,同时LPL升高以及PPARαmRNA表达量升高亦有统计学意义（P〈0．05）。结论：山楂叶提取物能够改善NAFLD大鼠的糖脂代谢异常,这可能与提高LPL的含量和增加PPARctmRNA表达有关。     

Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion

Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.     

A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response

The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention—Atlanta, and others.     

Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp's are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.     

Disease Pandemics and Major Epidemics Arising From New Encounters between Indigenous Viruses and Introduced Crops

Virus disease pandemics and epidemics that occur in the world’s staple food crops pose a major threat to global food security, especially in developing countries with tropical or subtropical climates. Moreover, this threat is escalating rapidly due to increasing difficulties in controlling virus diseases as climate change accelerates and the need to feed the burgeoning global population escalates. One of the main causes of these pandemics and epidemics is the introduction to a new continent of food crops domesticated elsewhere, and their subsequent invasion by damaging virus diseases they never encountered before. This review focusses on providing historical and up-to-date information about pandemics and major epidemics initiated by spillover of indigenous viruses from infected alternative hosts into introduced crops. This spillover requires new encounters at the managed and natural vegetation interface. The principal virus disease pandemic examples described are two (cassava mosaic, cassava brown streak) that threaten food security in sub-Saharan Africa (SSA), and one (tomato yellow leaf curl) doing so globally. A further example describes a virus disease pandemic threatening a major plantation crop producing a vital food export for West Africa (cacao swollen shoot). Also described are two examples of major virus disease epidemics that threaten SSA’s food security (rice yellow mottle, groundnut rosette). In addition, brief accounts are provided of two major maize virus disease epidemics (maize streak in SSA, maize rough dwarf in Mediterranean and Middle Eastern regions), a major rice disease epidemic (rice hoja blanca in the Americas), and damaging tomato tospovirus and begomovirus disease epidemics of tomato that impair food security in different world regions. For each pandemic or major epidemic, the factors involved in driving its initial emergence, and its subsequent increase in importance and geographical distribution, are explained. Finally, clarification is provided over what needs to be done globally to achieve effective management of severe virus disease pandemics and epidemics initiated by spillover events.     

Barrett's Esophagus: Where Do We Stand?

Barrett''s esophagus (BE) is a precursor for esophageal adenocarcinoma, which has an increased incidence rate over the last few decades. Its importance stems from the poor five-year survival of esophageal adenocarcinoma and current data that suggest a survival benefit when surveillance programs are implemented. In this review, we will cover the pathophysiology and natural history of BE and the different endoscopic findings. The prevalence of BE in different geographic areas and the incidence of high-grade dysplasia and adenocarcinoma in this patient population is reviewed. Recent recommendation for screening and surveillance of BE has been covered in this review as well as the efficacy of nonconventional imaging modalities and endoscopic ablation therapies.     

The Technology Transfer from Europe to China in the 17th–18th Centuries: Non-Invasive On-Site XRF and Raman Analyses of Chinese Qing Dynasty Enameled Masterpieces Made Using European Ingredients/Recipes

Two masterpieces of the Qing Dynasty (1644–1912 CE), one in gilded brass (incense burner) decorated with cloisonné enamels stylistically attributed to the end of the Kangxi Emperor’s reign, the other in gold (ewer offered by Napoleon III to the Empress as a birthday present), decorated with both cloisonné and painted enamels bearing the mark of the Qianlong Emperor, were non-invasively studied by optical microscopy, Raman microspectroscopy and X-ray microfluorescence spectroscopy (point measurements and mapping) implemented on-site with mobile instruments. The elemental compositions of the metal substrates and enamels are compared. XRF point measurements and mappings support the identification of the coloring phases and elements obtained by Raman microspectroscopy. Attention was paid to the white (opacifier), blue, yellow, green, and red areas. The demonstration of arsenic-based phases (e.g., lead arsenate apatite) in the blue areas of the ewer, free of manganese, proves the use of cobalt imported from Europe. The high level of potassium confirms the use of smalt as the cobalt source. On the other hand, the significant manganese level indicates the use of Asian cobalt ores for the enamels of the incense burner. The very limited use of the lead pyrochlore pigment (European Naples yellow recipes) in the yellow and soft green cloisonné enamels of the Kangxi incense burner, as well as the use of traditional Chinese recipes for other colors (white, turquoise, dark green, red), reinforces the pioneering character of this object in technical terms at the 17th–18th century turn. The low level of lead in the cloisonné enamels of the incense burner may also be related to the use of European recipes. On the contrary, the Qianlong ewer displays all the enameling techniques imported from Europe to obtain a painted decoration of exceptional quality with the use of complex lead pyrochlore pigments, with or without addition of zinc, as well as cassiterite opacifier.