硫酸软骨素A介导的恶性疟原虫感染的红细胞粘附

对硫酸软骨素的粘附机制进行了初步探讨。研究表明,恶性疟原虫感染的红细胞可粘附于各种器官的微血管内皮细胞,这种粘附被认为是红细胞膜表面分子与内皮细胞表面分子间配体－受体相互作用的结果,ＣＳＡ为内皮细胞表面感染的红细胞的粘附受体和恶性疟原虫红细胞膜蛋白１的配体。     

乙胺嘧啶与氯喹降低感染疟疾的BALB/c孕小鼠的胎盘病理样改变

怀孕期间患疟疾与胎儿死亡、流产、早产及低体重密切相关,在一些疟疾发病地区,常常使用乙胺嘧啶和氯喹来预防治疗,但它们对于胎盘的病理样改变尚未报道,本研究的目的即为探讨乙胺嘧啶和氯喹治疗怀孕的BALB/c小鼠感染伯氏疟原虫诱发的疟疾引起胎盘的病理样改变.购买BALB/c小鼠,随机分为6组,建立疟疾模型,并使用乙胺嘧啶和氯喹治疗处理,对相应组的疟疾感染情况、小鼠生存率、氧化水平、凋亡水平及组织病理改变情况进行检测分析.结果发现,被伯氏疟原虫感染后血液中被感染的红细胞比例显著上升(p<0.05),同时小鼠存活率显著降低(p<0.05),而乙胺嘧啶和氯喹不但可以降低感染红细胞的比例,还能提升小鼠的存活率(p<0.05);被感染的小鼠的脂质过氧化水平和过氧化氢酶水平显著上升(p<0.05),使用乙胺嘧啶和氯喹治疗后又显著下降(p<0.05),而谷胱甘肽和超氧化物歧化酶的变化则不具有统计学差异(p>0.05);被感染的小鼠的凋亡细胞比例、感染红细胞形态和组织病理色素沉积较未感染组显著上升(p<0.05),使用乙胺嘧啶和氯喹治疗后又显著下降(p<0.05).乙胺嘧啶和氯喹在治疗疟疾中,通过抑制氧化应激及细胞凋亡的发生,降低胎盘组织病理学改变,从而达到有效的治疗目的.     

青蒿素传奇

疟疾,民间俗称“打摆子”,是经按蚊叮咬或输入带疟原虫的血液而感染的虫媒传染病。雌性按蚊是疟原虫的携带者和传播疟疾的罪魁祸首。根据寄生于人体的疟原虫种类,疟疾可分为间日疟、三日疟、恶性疟及卵围疟,主要表现为周期性规律发作。成人疟疾患者一般先全身发冷,并有明显的寒战,10分钟至24小时后体温迅速上升,持续高热2～6小时后,患者全身大汗淋漓,     

国际工程项目疟疾疾病预防与治疗

疟疾是由携带疟原虫的按蚊叮咬传播,全球97个国家受其影响,以非洲中西部地区最为严重。该公司境外受影响的项目主要分布在西非加纳、尼日利亚和东非乌干达,目前已出现数例重症疟疾和恶性疟疾死亡病例。由于疟原虫耐药性的存在,疟疾复发的现象越来越多,而复发或多次感染将对健康的影响更大,这些都对境外项目员工身心健康构成一定威胁。     

2015年诺奖解读抗疟青蒿素——祝贺青蒿素发现工作获得诺贝尔奖

<正>缘起自有人类以来,疟疾就如影随形。四种能够感染人的疟原虫——间日疟原虫、恶性疟原虫、三日疟原虫和卵形疟原虫在上万年间,与人类展开了针锋相对的生存竞争,甚至人类的基因都为之变异。在西非和中非,人们演化出了Duffy血型,使得红细胞表面的Duffy抗原缺失,阻断了间日疟进入红细胞的通道。而针对危害性最大的恶性疟,非洲人还演化出了镰状细胞贫血,这是β珠蛋白基因单一碱基突变导致的性状,可将恶性     

科学家找到疟疾治疗“万能钥匙”

[科学时报]如果缺乏一种特殊的蛋白质，由疟蚊携带的疟原虫将无法感染红细胞。图片来源：威康信托基金会桑格研究所     

疟疾介绍

 疟疾俗称“打摆子”、“寒热病”,是由按蚊传播感染疟原虫而引起的一种寄生虫病,会引起脾肿大和贫血,重症疟疾患者可引发脑、肝、肾等器官损伤和循环系统、呼吸系统等功能衰竭,严重危害人类的健康和生命安全,影响社会经济的发展。     

恶性疟原虫(Plasmodium falciparum)在国产三种猴体内的繁殖

由于实验寄生虫学的迅速发展,特别是疟疾免疫的研究已进入了虫苗的研制阶段,疟疾动物模型的研究已日形重要。疟疾动物模型的研究,主要是从事寄生于人的两种最重要的疟原虫,即间日疟原虫(Plasmodium vivax)和恶性疟原虫(P. falciparum)实验寄主的研究,至今已有将近一百年的历史。到目前为止,只有少数的灵长类被证实对这两种疟原虫有不同程度的感受性。在这方面近年来曾有文献综述。我们在1973和1974两年间,在广西百色地区以恶性疟患者的鲜血,直接静注接种于猕猴(Macaca mutatta)22只,熊猴(M. assamensis)9只,黑叶猴(Presbytis francicoisi)7只,在11只猕猴、5只熊猴和4只黑叶猴的外周血液中皆看到原虫无性发育的各个时期和配子母体的形成。但除在黑叶猴体内所见的配子母体较接近于成     

“蚊子疫苗”:阻断疟疾流行

正近期,国际顶级学术期刊《Science》(第340期)刊登中山大学—密歇根州立大学虫媒控制疟疾研究最新成果——《沃尔巴克氏体侵入斯氏按蚊种群中并诱导对疟原虫感染的抗性》(Wolbachia invade Anopheles stephensi Populations and Induces Refractoriness to Plasmodium Infection)。这项发明也许将为科学家和全球卫生机构解决世界上最主要的虫媒病——疟疾,提供一件利器。该研究由中山大学—密歇根州立大学热带病虫媒控制联合研究中     

普通棉耳狨猴中乙型流感病毒的分离和鉴定

乙型流感病毒是引起人类局部流行性感冒的重要病原体，其起源和自然储存宿主目前仍不清楚。1999年夏季在某动物中心饲养的普通棉耳绒猴（Callithrix jacchus）群体中爆发了以呼吸道症状为主的急性传染病，死亡比率高达1／3。通过对死亡狨猴肺组织匀浆接种鸡胚和MDCK细胞的分离培养，分离出病毒。双份血清的红细胞凝集抑制试验证实，此分离株为此次狨猴群体感染流行的病原体。通过甲型和乙型流感病毒标准血清鉴定，证实该分离株为乙型流感病毒，命名为B/marmoset/China/1/99。     

A 2020 vision for vaccines against HIV, tuberculosis and malaria

Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.     

Genetically modified Plasmodium parasites as a protective experimental malaria vaccine

Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes, transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites. Liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection. Using expression profiling, we previously identified genes that are only expressed in the pre-erythrocytic stages of the parasite. Here, we show by reverse genetics that one identified gene, UIS3 (upregulated in infective sporozoites gene 3), is essential for early liver-stage development. uis3-deficient sporozoites infect hepatocytes but are unable to establish blood-stage infections in vivo, and thus do not lead to disease. Immunization with uis3-deficient sporozoites confers complete protection against infectious sporozoite challenge in a rodent malaria model. This protection is sustained and stage specific. Our findings demonstrate that a safe and effective, genetically attenuated whole-organism malaria vaccine is possible.     

基因疫苗研究与进展

基因疫苗代表了新的、具有潜力的疫苗发展途径和研究方向，它取得成功主要归功于基因治疗技术的发展．基因疫苗是直接将抗原的编码基因注入动物体内，并在动物细胞中表达抗原蛋白以诱导动物产生免疫保护作用．基因疫苗研究有可能为当今人类无法控制的一些严重传染疾病，提供新的免疫防治途径和手段．本文回顾了基因疫苗发展历史和研究进展，与传统疫苗相比较，对基因疫苗的作用原理、构造以及技术方法等方面的初步研究和进展情况进行了概述。     

Cloning and expression in E. coli of the malarial sporozoite surface antigen gene from Plasmodium knowlesi

The malarial sporozoite, the infective stage found in the salivary gland of the insect vector, bears highly immunogenic surface antigen(s). Repeated exposure to irradiated sporozoites induces protection against malaria in several host species, including man. Further, monoclonal antibodies that confer passive immunity react with the immunogenic surface determinants of different sporozoite species. One approach to prevent malaria, therefore, would be to produce a vaccine that induces high titres of circulating antibodies against the sporozoite surface determinant(s). However, production of such a vaccine has not been possible since sporozoites cannot be cultivated in vitro and, therefore, only limited amounts of surface antigen may be obtained. To overcome this problem, we have prepared mRNA from Plasmodium knowlesi-infected mosquitoes to construct a cDNA library. From this library we have isolated a clone that expresses the sporozoite surface antigen as a beta-lactamase fusion protein in the plasmid pBR322. This is the first potentially protective malarial antigen to be cloned by recombinant DNA technology.     

Progress and challenges for malaria vaccines

Malaria causes much physical and economic hardship in tropical regions, particularly in communities where medical care is rudimentary. Should a vaccine be developed, it is the residents of these areas that stand to benefit the most. But the vaccine, which has been promised to be 'just round the corner' for many years, remains elusive. It is important to ask why this is so, when effective vaccines exist for many other infectious diseases. What are the reasons for the slow rate of progress, and what has been learned from the first clinical trials of candidate malaria vaccines? What are the remaining challenges, and what strategies can be pursued to address them?     

Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites

A 12 amino-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (TT), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. Seroconversions against NANP occurred in 53% and 71% of recipients of 100 or 160 micrograms, respectively, measured by enzyme-linked immunosorbent assay (ELISA). Most ELISA-positive sera reacted with sporozoites by indirect immunofluorescence (IFA). Three vaccinees with the highest ELISA and IFA titres and four unimmunized controls were challenged with P. falciparum sporozoites introduced via the bites of infective Anopheles mosquitoes. Blood stage parasites were detected in all controls by 10 days (mean 8.5 days, range 7-10). In contrast, the two vaccinees who became infected did not manifest parasitaemia until day 11 and the third vacinee showed neither parasites nor symptoms during the 29 day observation period. This first synthetic peptide parenteral vaccine against a communicable disease tested in man is safe and stimulates biologically active antibodies. These observations encourage the development of improved vaccine formulations which, by enhancing immunogenicity, may lead to practical vaccines to assist in the control of falciparum malaria.     

The pathogenic basis of malaria

Malaria is today a disease of poverty and underdeveloped countries. In Africa, mortality remains high because there is limited access to treatment in the villages. We should follow in Pasteur's footsteps by using basic research to develop better tools for the control and cure of malaria. Insight into the complexity of malaria pathogenesis is vital for understanding the disease and will provide a major step towards controlling it. Those of us who work on pathogenesis must widen our approach and think in terms of new tools such as vaccines to reduce disease. The inability of many countries to fund expensive campaigns and antimalarial treatment requires these tools to be highly effective and affordable.     

预防商品混凝土开裂的早期养护措施

通过试验观测,分析不同养护条件下商品混凝土早期收缩裂缝发生和发展规律．文中指出提高混凝土早期强度和及早养护,可减小混凝土内部应力(包括收缩应力和温度应力)．加强早期养护既可提高混凝土初始强度,又可减小混凝土内部应力,是减少混凝土裂缝的有效手段．     

Inhibition of P. falciparum growth in human erythrocytes by monoclonal antibodies

Malaria is increasing in incidence and prevalence in most tropical areas and is a major problem for both individuals and communities. Current malaria research is aimed at developing vaccines and, for this, it may be useful to define Plasmodium antigen(s) related to the development of a protective immune response in the host. Monoclonal antibodies have recently been shown to interfere with rodent malaria infection (Plasmodium berghei) at the sporozoite or merozoite stage. We have now raised monoclonal antibodies against single antigenic determinant(s) of Plasmodium falciparum and report that some of them inhibit the growth of erythrocytic forms of P. falciparum in vitro.     

Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria

The malaria parasite Plasmodium falciparum infects 5-10% of the world's population and kills two million people annually. Fatalities are thought to result in part from pathological reactions initiated by a malarial toxin. Glycosylphosphatidylinositol (GPI) originating from the parasite has the properties predicted of a toxin; however, a requirement for toxins in general and GPI in particular in malarial pathogenesis and fatality remains unproven. As anti-toxic vaccines can be highly effective public health tools, we sought to determine whether anti-GPI vaccination could prevent pathology and fatalities in the Plasmodium berghei/rodent model of severe malaria. The P. falciparum GPI glycan of the sequence NH(2)-CH(2)-CH(2)-PO(4)-(Man alpha 1-2)6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcNH(2)alpha 1-6myo-inositol-1,2-cyclic-phosphate was chemically synthesized, conjugated to carriers, and used to immunize mice. Recipients were substantially protected against malarial acidosis, pulmonary oedema, cerebral syndrome and fatality. Anti-GPI antibodies neutralized pro-inflammatory activity by P. falciparum in vitro. Thus, we show that GPI is a significant pro-inflammatory endotoxin of parasitic origin, and that several disease parameters in malarious mice are toxin-dependent. GPI may contribute to pathogenesis and fatalities in humans. Synthetic GPI is therefore a prototype carbohydrate anti-toxic vaccine against malaria.