Epinephrine versus dopamine to treat shock in hypoxic newborn pigs resuscitated with 100% oxygen

Shock and tissue hypoperfusion are common after asphyxia. We compared systemic and regional hemodynamic effects of epinephrine and dopamine in the treatment of shock and hypotension in asphyxiated newborn piglets resuscitated with 100% oxygen. Twenty-four piglets (1-3 days old; weight, 1.4-2.6 kg) were acutely instrumented to measure cardiac index (CI), carotid, mesenteric and renal arterial blood flows, and mean systemic (SAPs) and pulmonary arterial pressures (PAPs). Piglets had normocapnic alveolar hypoxia (F(IO2)=0.08-0.10) for 50 min and reoxygenated with F(IO2)=1.0 for 1 h then F(IO2)=0.21 for 3.5 h. After 2 h reoxygenation, either dopamine (2 microg kg(-1) min(-1)) or epinephrine (0.2 microg kg(-1) min(-1)) was given for 30 min in a blinded randomized manner, which was then increased to maintain SAP (within 10% of baseline, pressure-driven dose) for 2 h. Hypoxia caused hypotension (SAP, 44%+/-3% of baseline), cardiogenic shock (CI, 41%+/-4%), and metabolic acidosis (mean pH, 7.04-7.09). Upon reoxygenation, hemodynamic parameters immediately recovered but gradually deteriorated during 2 h with SAP at 45+/-1 mmHg, CI at 74+/-9% of baseline, and pH 7.32+/-0.03. Low doses of either drug had no significant systemic and renal hemodynamic response. Epinephrine (0.3-1.5 microg kg(-1) min(-1)) for 2 h increased SAP and CI (with higher stroke volume) and decreased pulmonary vascular resistance (with reduced PAP-SAP ratio), whereas the responses with dopamine (10-25 microg kg(-1) min(-1)) were modest. Low-dose epinephrine improved mesenteric and carotid arterial flows, whereas the pressure-driven doses of epinephrine and dopamine increased carotid and mesenteric arterial flows, respectively. To treat shock in asphyxiated newborn piglets resuscitated with 100% oxygen, epinephrine exhibits an inotropic action compared with dopamine, whereas both catecholamines can increase carotid and mesenteric perfusion.     

Objective tools to analyze the lower lateral cartilage in unilateral cleft lip nasal deformities

Correction of cleft lip nasal deformity is an elusive goal. A controversy exists regarding the cause of the deformity, and therefore, there is a controversy of how to correct the deformity. Extrinsic theory is based on the presence of deformational forces from outside. The intrinsic theory is associated with deficiency of the lower lateral cartilage. The aim of this study was to use new objective tools to compare morphologically and histologically between the lower lateral cartilages of cleft and noncleft sides in patients with unilateral cleft lip nasal deformity. This study included 16 patients. They were operated on to correct unilateral cleft lip nasal deformity. Length, width, and thickness of lateral crura of the lower lateral cartilages of cleft and noncleft sides were measured. Punch biopsies from the middle part of the caudal ends of lateral crura were taken and sent for histologic and immunohistochemical studies. The lateral crura of the cleft side were significantly wider and shorter and tend to be thinner than those of the noncleft side. There was no significant difference in the chondroblast, chondrocyte, and total cellular number in the lower lateral cartilage of the cleft and noncleft sides. There was significantly less glycosaminoglycan content in the ground matrix of the lower lateral cartilage of cleft side. In conclusion, the use of digital sliding caliber in measuring the diminutions of the lower lateral cartilage and image analyzer to quantify the proteoglycans, glycosaminoglycans, fibroblast growth factor 18, and collagen content is very effective objective tools to compare the cleft and noncleft alar cartilage.     

Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly

The West Nile virus minus-strand 3' terminal stem loop (SL) RNA was previously shown to bind specifically to cellular stress granule (SG) components, T cell intracellular antigen-1 (TIA-1) and the related protein TIAR. In vitro TIAR binding was 10 times more efficient than TIA-1. The 3'(-)SL functions as the promoter for genomic RNA synthesis. Colocalization of TIAR and TIA-1 with the viral replication complex components dsRNA and NS3 was observed in the perinuclear regions of West Nile virus- and dengue virus-infected cells. The kinetics of accumulation of TIAR in the perinuclear region was similar to those of genomic RNA synthesis. In contrast, relocation of TIA-1 to the perinuclear region began only after maximal levels of RNA synthesis had been achieved, except when TIAR was absent. Virus infection did not induce SGs and progressive resistance to SG induction by arsenite developed coincident with TIAR relocation. A progressive decrease in the number of processing bodies was secondarily observed in infected cells. These data suggest that the interaction of TIAR with viral components facilitates flavivirus genome RNA synthesis and inhibits SG formation, which prevents the shutoff of host translation.     

脐血干细胞和胎盘间充质干细胞在妇产科应用中的前景

目的:介绍脐血干细胞和胎盘间充质干细胞的研究进展,以及干细胞在妇产科中的应用前景。资料来源:应用计算机检索Medline1996-01/2006-12与脐血干细胞和胎盘间充质干细胞、以及干细胞在妇产科中的应用相关的文章,检索词为“human cord blood,mesenchy malstem cell,placenta,gene therapy in the uterus”,限定文献语种为“English”;同时检索万方数据库2000-01/2006-12相关文章,检索词为“脐血,间充质干细胞,胎盘,宫内治疗,卵巢癌,子宫癌”,限定文献语种为中文。资料选择:共检索到相关文献500余条,进一步查找全文,优先选择与临床应用靠近的文章,无论观察对象是人还是动物均纳入,筛除干细胞的提取、分化或培养等基础类研究,明显重复和综述文献也排除,最后纳入31条文献进行综述。资料提炼:31条文献中论述脐血干细胞和胎盘间充质干细胞的特点及应用文章有26篇,关于宫内移植干细胞治疗的文章有2篇,其他为研究干细胞在妇产科中应用的文章。资料综合:①大量实验证明脐血是骨髓、外周血后的第3种非常有潜力的造血干细胞资源。目前应用脐血移植治疗的疾病有急(慢)性白血病、恶性淋巴瘤、多发性骨髓瘤、再生障碍性贫血、严重免疫缺陷症等,而且已经有一定疗效。②胎盘作为胚胎发育中维系母体和胎儿氧气及营养物质交换的重要暂时性器官,无论从解剖结构还是在发育行为上,都包含了较为幼稚的胚胎及趋于成熟的成体干细胞成分,而且胎盘不会涉及伦理道德问题,目前已成为寻找人类间充质干细胞新来源及提高临床应用效果的研究热点。③干细胞宫内移植为先天性疾病治疗开辟了一条新途径。另外干细胞在器官再造、男性不育治疗和保存生育能力等生殖医学领域的研究也取得了重大进展,在妇科肿瘤方面,如以化疗保护为目标的基因治疗已逐步应用于临床。结论:脐血和胎盘取材方便、安全,还能避免免疫排斥和伦理问题,已成为人类间充质干细胞新来源。干细胞在宫内治疗、生殖疾病和妇科肿瘤方面也有广泛的临床应用前景。     

筛选心肌缺血再灌注大鼠差异表达基因

目的：利用抑制性消减杂交技术，筛选出大鼠心肌缺血再灌注的差异表达基因，以期通过基因线索探讨其损伤机制。方法：实验于2006—03／10在中山大学中山医学院完成。①实验分组：Sprague-Dawley雄性大鼠40只，随机分为手术组，对照组，每组20只。②实验干预：手术组结扎左冠状动脉，心电图出现急性心肌梗死改变90min后，去除结扎线，再灌注60min，建立心肌缺血再灌注大鼠模型。对照组仅穿线不结扎，余同手术组。③取缺血区心肌，提取Total RNA，构建cDNA文库，利用抑制性消减杂交技术筛选差异表达基因，测序，登录Genbank寻找同源性基因。结果：共获得124个阳性结果，56个为高表达基因，68个为低表达基因，其中发现5个新的cDNA片段。其中能量代谢、物质运输、信号转导相关差异表达基因分别占所有差异表达基因的39．25％，15．89％，15．89％，并且主要变化为下调。结论：抑制性消减杂交技术是一种高效的筛选差异基因的方法。心肌缺血再灌注后基因变化涉及多种功能的基因，以能量代谢、物质运输、信号转导相关基因下调明显。