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1.
Lymphatic filariasis caused mainly by infection fromWuchereria bancrofti andBrugia malayi remains as the major cause of clinical morbidity in tropical and subtropical countries. Development of vaccine against filarial infection can act as additional measure to the existing therapeutic and vector control methods in the control of this disease. The main hurdles in the development of anti-filarial vaccine are the strict primate specificity ofWuchereria bancrofti, the paucity of parasite material, the diversity of clinical manifestations and their associated complex immune responses, lack of clear understanding on host-parasite interactions and the mechanisms involved in protective immunity. However in the past few years, the information generated in immuno-epidemiological studies, correlated with observations in experimental animals suggests that a filarial vaccine is feasible. Initially live irradiated infective larvae have been successfully used to induce high level of protective immunity in several animal models. Applying diverse strategies, variety of purified or recombinant filarial antigens have been explored for their ability to induce protection in different host-parasite systems. Some of these targeted filarial antigens induced high level of resistance in experimental animals against challenge infections. More focussed studies on thorough characterization of parasitological and immunological changes associated with resistance induced by such candidate protective antigens and on delivery mechanisms and safety aspects will be crucial in their selection for possible use in humans.  相似文献   

2.
Little is known about host-parasite inter-relationship in the lymphatic filarial parasites. There is no information available about the ability of these parasites to acquire cholesterol, though it is known that in general, nematodes lack the ability to synthesise cholesterolde novo. In this study, we have shown that the filarial parasites also lack the ability to incorporate labelled acetate into cholesterol, indicating the absence of the machinery for cholesterol biosynthesis. We have further shown that they elaborate a 43 kDa surface receptor for acquiring LDL-bound cholesterol. We have shown by polymerase chain reaction the presence of a 860 bp fragment indicating the presence of the gene for LDL-related protein (LRP) in the human filarial parasiteWuchereria bancrofti in the genomic DNA. We have also shown that it is expressed as seen in the cDNA clones identified from an expression library.  相似文献   

3.
Human lymphatic filariasis is a chronic helminth infection caused byWuchereria bancrofti andBrugia malayi. Wide spectrum of clinical manifestations are seen in different clinical groups of filariasis patients which comprises asymptomatic patients with circulating microfilaria (MF), individuals with chronic lymphatic obstruction (CP), Endemic normals (EN) who are asymptomatic and amicrofilaraemic or the relatively rare tropical pulmonary eosinophilia (TPE). The cellular immune response to this infection varies in different clinical groups of filarial patients. ranging from normal lymphocyte proliferative response in EN individuals to lymphocyte hyporesponsiveness in MF to total parasite antigen [Brugia malayi antigen (BMA)]. But in response to recombinant filarial antigen (pRJ51) the lymphocyte proliferation is restored in MF patients. Interestingly the lymphocytes from MFs responded normally to parasite antigen when EN serum was added in the culture whereas sera from MFs failed to revert the lymphocyte hyporesponsiveness. In order to study the molecular mechanisms responsible for parasite antigen specific lymphocyte hyporesponsiveness, we analysed both the Th1 and Th2 type cytokine gene expression profile in different clinical groups of filarasis patients. MF individuals expressed elevated Th2 type cytokines like IL-4, IL-5 and IL-10 and decreased levels of IL-2 and IFN-γ in response to parasite antigen. Chronic patients have elevated levels of both Th1 and Th2 type cytokines in response to parasite antigen. The EN individuals had a purely Th1 type pattern with absence of IL-4 and IL-5 expression. These studies clearly demonstrate the role of Th2 cytokine like IL-10 in antigen specific hyporesponsiveness seen in MF patients. Any methods to arrest the progression of this disease should concentrate on the means to revert the Th2 type into Th1 type response in the MF patients either by Th1 type cytokine therapy or by using recombinant filarial antigen which stimulates the Th1 response. Further the recombinant filarial antigen which induces Th1 type cytokine response could be used for immunoprophylactic studies.  相似文献   

4.
WHO-Tropical Disease Research scheme highlighted the need for development of new anti-filarial drugs. Certain antibiotics have recently been found effective against Wolbachia, co-existing symbiotically with filarial parasites. Inflammatory response entails oxidative mechanism to educe direct anti-microbial effect. In the present study microfilariae were maintained in vitro in medium supplemented with varying concentrations of tetracycline, doxycycline (20–100 μg/ml) or ciprofloxacin (50–250 μg/ml) separately to find out any involvement of oxidative mechanism in the anti-filarial effect of these antibiotics. Loss of motility of the microfilariae was measured after 48 h and correlated with the levels of MDA, nitric oxide and protein-carbonylation. Significant loss of microfilarial motility was recorded with increasing concentration of tetracycline and doxycycline but with ciprofloxacin the effect was not marked. Agents with high antifilarial activity revealed significant association with oxidative parameters in a dose dependent manner. The result suggests that oxidative effect might be exploited to design novel antifilarial drug candidate.  相似文献   

5.
Lymphatic filariasis continues to be the major cause of clinical morbidity in India and other developing tropical countries. One of the major lacunae in the effective management of clinical filarial cases is the non-availability of a suitable diagnostic test for confirming filaria aetiology in acute, chronic and occult clinical cases where microfilariae (mf) are not usually seen in peripheral circulation. Studies in our laboratory have shown the usefulness of filarial antibody and antigen assays using microfilarial excretory-secretory (mf ES) antigen in detecting microfilaraemic, acute and chronic filarial cases and in confirming filarial aetiology in occult infections. Diethylcarbamazine citrate (DEC) is the drug of choice for lymphatic filariasis. Different regimens of DEC have been explored in the treatment of microfilaraemic cases. Immunomonitoring has shown that the seroconversion of antigen and antibody positivity was found to be very helpful in determining appropriate period of DEC treatment for clinical relief and cure in clinical filarial patients and further they did not have recurrence in most of the cases. Optimal DEC (6mg/kg body wt/day for 21 days each month for 3–12 months) therapy was found to be very effective in acute and atypical clinical manifestations such as asthmatic bronchitis, pulmonary eosinophilia, monoarthritis, recurrent upper respiratory tract infections (URI), pneumonia (super imposed infections) in children and minimal hydrocele, epididymoorchitis, lymphangitis, lymphadenitis, acute abdomen, central serous retinopathy, tenosynovitis, pain and swelling in limbs and joints in adults living in filaria endemic areas.  相似文献   

6.
In vitro released antigens by living parasites or bacteria underin vitro maintenance or short term culture showing specific humoral immune response have been explored in development of immunodiagnostics for infectious diseases such as filariasis and tuberculosis in our laboratory. ELISA usingB. malayi mf ES antigen has been explored for detecting IgG antibody by Indirect ELISA and antigen by Inhibition ELISA and in immunomonitoring of carriers as well as clinical filarial cases. A ten year follow up of mf carriers with DEC therapy showed disapperance of antigen and antibody followed by reappearance in few cases in an endemic area. None of the cases followed developed clinical symptoms suggesting the need for long term monitoring and treatment of microfilaraemic carriers. Further immunomonitoring was found to be useful in confirming filaria aetiology in the absence of microfilaremia and determining appropriate period of treatment of acute, early clinical and occult filarial infections for clinical relief and cure.Indirect Stick Penicillinase ELISA system using Mtb EST-6 antigen for detecting tuberculous IgG antibody and a Sandwich Penicillinase ELISA system using affinity purified antibody for detecting circulating antigen were explored in tuberculosis. A combination of both the assay systems with a sensitivity of 70% and specificity of 98% was found to be promising in the precise diagnosis of pulmonary tuberculosis. Further antigen detection was found to be useful in bone and joint tuberculosis.  相似文献   

7.
8.
A comparative analysis was made on the utility of SEVAFILACHEK-stick based immunoassays and commercially available ICT-filariasis test to detect active infection in different groups of bancroftian filariasis. The SEVAFILACHEK immunoassays were found to be useful to detect filarial infection in microfilaraemia and in a significant number of clinical filarial cases with acute, chronic and occult clinical manifestations. In the clinical cases, microfilariae are not usually detected in peripheral circulation. Employing SEVAFILACHEK assays 6 and 5 of the 7 samples of patients with chronic filarial disease, and 6 and 5 of 6 microfilaraemic cases gave positivity for filarial IgG antibodies and antigen respectively. Four of the 6 occult filarial samples were positive for antibodies and antigen. Filarial antigen was detected by ICT-filariasis test in blood samples of all the 6 microfilariaemic cases, 1 chronic filarial and 2 occult filarial samples. The main advantage of ICT assay is its rapid format and convenience for field use.  相似文献   

9.
全球气候变暖,极端天气频发,入侵型、新发和重发昆虫传作物病毒病害已经成为限制我国农作物优质高产的主要因素。因缺乏抗病抗虫的种质资源、育种周期长,虫传病害防治难度极大,目前我国农业处于几乎完全依赖化学防控媒介昆虫的被动应付局面,生态与环境成本极大。以往研究虫传病毒病害往往注重病毒和植物寄主两个方面,这些研究为理解作物病毒病害的暴发机制提供了基础知识,但尚未能深入到病害防控的关键节点——媒介昆虫介导的病毒侵染循环这一根本性问题上,导致目前在病毒病害防治实践上缺乏有效抓手。近年来,随着分子生物学和组学研究的飞速发展,以及微观生物学技术和理念对宏观生物学的快速渗透与交叉,病毒—昆虫—植物三者互作机制研究取得了诸多重要进展,在寻找病毒病害流行暴发的宏观生态学现象背后的分子生物学与生物化学机制上取得了长足进步,不但为复杂生态系统多元互作分子机制提供了参考模型,也为通过人工干扰和操纵生物间互作关键节点,从而促进虫传病毒病害的持久防控提供了科学依据和新的有效抓手,变被动应付为主动调控病害灾变过程。文章简要回顾了近年来病毒—昆虫—植物三者互作领域的主要研究进展和发展趋势,并抛砖引玉提出了对未来发展的建议和思考。建议国家组织研究力量,大力加强:(1)大田生产条件下病毒病害发生的多元生物体系互作机制及科学防控科技支撑能力建设;(2)前沿基础和新方法新策略探索及应用平台建设;(3)虫媒病害绿色防控的微生物组学颠覆性技术等方向的探索与突破,力求在虫传作物病毒病害绿色生态防控方面为农业供给侧改革提供强有力的科技创新和支撑能力。  相似文献   

10.
The development of local technology-intensive suppliers (t-suppliers) may contribute to both reinforcing the industrial base and supporting the competitiveness of primary production in developing countries. This article explores the role of t-suppliers in natural resource-based economies and outlines a theoretical framework for the analysis of the factors which foster or constrain their development and defines areas for an effective promotion. The proposed model of analysis distinguishes between factors influencing the development of t-suppliers on the level of the main industry, the level of supplier firms or firm-level and the level of external determinants with special reference to industrial policy factors.  相似文献   

11.
Clonorchis sinensis or the Chinese liver fluke is one of the most prevalent parasites affecting a major population in the oriental countries. The parasite lacks lipid generating mechanisms but is exposed to fatty acid rich bile in the liver. A secretory phospholipase A2, an enzyme that breaks down complex lipids, is important for the growth of the parasite. The enzyme is also implicated in the pathogenesis leading up to the hepatic fibrosis and its complications including cancer. The five isoforms of this particular enzyme from the parasite therefore qualify as potential drug targets. In this study, a detailed structural and ligand binding analysis of the isoforms has been done by modeling. The overall three dimensional structures of the isoforms are well conserved with three helices and a β-wing stabilized by four disulfide bonds. There are characteristic differences at the calcium binding loop, hydrophobic channel and the C-terminal domain that can potentially be exploited for drug binding. But the most significant feature pertains to the catalytic site where the isoforms exhibit three variations of either a histidine-aspartate-tyrosine or histidine-glutamate-tyrosine or histidine-aspartate-phenylalanine. Molecular docking studies show that isoform specific residues and their conformations in the substrate binding hydrophobic channel make unique interactions with certain inhibitor molecules resulting in a perfect tight fit. The proposed ligand molecules have a predicted affinity in micro-molar to nano-molar range. Interestingly, few of the ligand binding interaction patterns is in accordance to the phylogenetic studies to thereby establish the usefulness of evolutionary mechanisms in aiding ligand design. The molecular diversity of the parasitic PLA2 described in this study provides a platform for personalized medicine in the therapeutics of clonorchiasis.

Electronic supplementary material

The online version of this article (doi:10.1007/s12291-013-0377-1) contains supplementary material, which is available to authorized users.  相似文献   

12.
13.
This paper explores the implications of environmental conditions related to computer-based information systems (CBIS) development and implementation in developing countries. Their different economic, social, infrastructural, educational, cultural, political and legal conditions have important implications for organizational information requirements and cost/benefit considerations. This suggests that strategies based on a systems approach for information systems development in those countries should be adapted to minimize costly mistakes and to increase effectiveness. By examining environmental conditions in developing countries and their effects on the system development process, this paper proposes general directions for CBIS development to organizations in these countries.  相似文献   

14.
The possibilities and limitations of chemical reaction names as the basis for retrieving literature dealing with reaction types are briefly reviewed, as well as the capability of a mere substructure search in a file of reactants and products. It is demonstrated that reaction indexing ideally should be based on the identification of the reaction sites of the molecules involved, as well as on the representation of various kinds of relations between these reactive centers. The GREMAS reaction indexing of IDC is discussed as an example. Before a chemist can request information on reaction types that appear promising for a certain target molecule, he must be aware of their existence. The task of computer-assisted synthesis design is to submit suggestions of conceivable synthetic pathways to a target structure and so to alert the chemist to syntheses of which he had not yet been aware. The “reverse retrieval” technique is demonstrated to constitute a fundamental principle for this kind of information supply. If sufficiently developed and assisted by an effective system for the documentation and classification of reaction types, it can provide suggestions for syntheses at a considerable efficiency without requiring completion by additional principles. The IDC system of (Sub-) Structure search seems to be able to serve this purpose too, due to its flexibility, economics, and precision. The reverse retrieval offers solutions to a number of problems hitherto unresolved in information science.  相似文献   

15.
In many cases, a target or a structure on a target may have micro-motions, such as vibrations or rotations. Micro-motions of structures on a target may introduce frequency modulation on the returned radar signal and generate sidebands on the Doppler frequency shift of the target's body. The modulation due to micro-motion is called the micro-Doppler (m-D) phenomenon. In this paper, we present an effective quadratic time-frequency S-method-based approach in conjunction with the Viterbi algorithm to extract m-D features. For target recognition applications, mainly those in military surveillance and reconnaissance operations, m-D features have to be extracted quickly so that they can be used for real-time target identification. The S-method is computationally simple, requiring only slight modifications to the existing Fourier transform-based algorithm. The effectiveness of the S-method in extracting m-D features is demonstrated through the application to indoor and outdoor experimental data sets such as rotating fan and human gait. The Viterbi algorithm for the instantaneous frequency estimation is used to enhance the weak human m-D features in relatively high noise environments. As such, this paper contributes additional experimental m-D data and analysis, which should help in developing a better picture of the human gait m-D research and its applications to indoor and outdoor imaging and automatic gait recognition systems.  相似文献   

16.
技术路线图(TRM)作为一种有效的科研管理工具,自研发以来就受到广大学者的高度关注并逐步应用于各种领域。但目前技术路线图通常不能有效揭示背后的驱动因素,且层次相对单薄,通常只包含技术、产品和市场三个层次,在实际应用中并不能为企业或行业发展提供详细指导。为解决这些问题,本文基于SAO结构信息构建了包含材料、技术、影响因素、产品、目标和应用六个层次的技术路线图,不仅揭示了领域内技术研发的驱动因素且提供了目标技术领域详细的发展路径,极具参考价值。最后,本文以瑞士学者在染敏太阳能电池技术领域的研究成果为案例,证实了该方法的可行性和有效性。, 技术路线图(TRM)作为一种有效的科研管理工具,自研发以来就受到广大学者的高度关注并逐步应用于各种领域。但目前技术路线图通常不能有效揭示背后的驱动因素,且层次相对单薄,通常只包含技术、产品和市场三个层次,在实际应用中并不能为企业或行业发展提供详细指导。为解决这些问题,本文基于SAO结构信息构建了包含材料、技术、影响因素、产品、目标和应用六个层次的技术路线图,不仅揭示了领域内技术研发的驱动因素且提供了目标技术领域详细的发展路径,极具参考价值。最后,本文以瑞士学者在染敏太阳能电池技术领域的研究成果为案例,证实了该方法的可行性和有效性。  相似文献   

17.
In this article we propose that medical practice evolves as a result of progress along three different pathways: improvement in the ability to develop effective medical technologies, learning in medical practice, and advances in biomedical scientific understanding of disease. The relative importance of these three pathways varies from case to case, and often they interact strongly. More specifically, we argue here that in cases of therapeutic innovation where a new medical technology is involved the advance in medical practice is driven largely by the ability to develop and use effective medical artifacts and the interactive sequence among these interdependent pathways often starts with what is learned in practice and not in science. While we state this argument in general, we develop it in detail in a longitudinal and contextual case study of the emergence and evolution of a treatment for advanced heart failure based on an implantable device, the Left Ventricular Assist Device (LVAD). Our findings show that an essential aspect of the evolution of the LVAD therapy is collective and cumulative learning that requires experience that only can be gained through the actual use of LVADs. We discuss the theoretical and policy implications that follow from our understanding of how medical practice evolves for research on the evolution of medical practices and new medical technologies, and policies about the evaluation of rapidly moving medical practices and clinical research involved in their advancement.  相似文献   

18.
Sera samples of 7 microscopic haematuria cases collected before and after treatment with Diethylcarbamazine citrate, (DEC), 9 microfilaraemic cases and 19 endemic normal individuals were analysed for filarial antigen and IgG antibody levels. Filarial antigen was detected in 5 of the 7 microscopic haematuria cases, of which 3 turned negative for antigen after treatment with DEC. While none of the 7 haematuria cases were positive for filarial IgG antibodies, before the DEC treatment, all of them turned positive after DEC treatment. The sensitivity and specificity values(to detect mf +ve cases) were 89% and 90% respectively for the detection of filarial antigen and 78% and 95% respectively for the detection of filarial IgG antibodies.  相似文献   

19.
国家“双一流”建设要求高校加强战略性、全局性、前瞻性问题研究,努力提升解决重大问题能力和原始创新能力。在此背景下,地方高校如何采取有效措施顺应新时代对高校科技发展的要求,提升自身的科研实力是关键。本文以某地方高校为例,分析了科研管理中目标考核体系构建的意义,研究了构建的内容、原则和步骤,提出了地方高校应构建科学合理的科研目标考核体系,采取有效的目标考核和奖惩,才能顺应“双一流”建设要求,提升自身的科研水平。  相似文献   

20.
付欣  付帅 《科技通报》2012,28(6):96-97,100
数字电路的测试生成通常是求解一个或一组测试矢量,这些测试矢量能够激活原始故障,并将这些故障效应传递到最终的输出端。测试集优化的基本目标是确定有效的测试矢量,即通过这些测试向量可以区分电路的正常状态与故障状态。目前随着各种智能优化算法的深入研究发展,针对测试集的优化方案也成为了这些智能策略发挥的舞台。  相似文献   

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